Ignite Creation Date:
2025-12-24 @ 2:14 PM
Ignite Modification Date:
2026-04-22 @ 12:37 PM
Study NCT ID:
NCT02366195
Status:
COMPLETED
Last Update Posted:
2021-11-30
First Post:
2014-11-11
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Single-arm Trial to Evaluate the Role of the Immune Response to Talimogene Laherparepvec in Unresected Melanoma
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D008545', 'term': 'Melanoma'}], 'ancestors': [{'id': 'D018358', 'term': 'Neuroendocrine Tumors'}, {'id': 'D017599', 'term': 'Neuroectodermal Tumors'}, {'id': 'D009373', 'term': 'Neoplasms, Germ Cell and Embryonal'}, {'id': 'D009370', 'term': 'Neoplasms by Histologic Type'}, {'id': 'D009369', 'term': 'Neoplasms'}, {'id': 'D009380', 'term': 'Neoplasms, Nerve Tissue'}, {'id': 'D018326', 'term': 'Nevi and Melanomas'}, {'id': 'D012878', 'term': 'Skin Neoplasms'}, {'id': 'D009371', 'term': 'Neoplasms by Site'}, {'id': 'D012871', 'term': 'Skin Diseases'}, {'id': 'D017437', 'term': 'Skin and Connective Tissue Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'C000629782', 'term': 'talimogene laherparepvec'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'medinfo@amgen.com', 'phone': '866-572-6436', 'title': 'Study Director', 'organization': 'Amgen Inc.'}, 'certainAgreement': {'otherDetails': "The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.", 'restrictionType': 'OTHER', 'piSponsorEmployee': False, 'restrictiveAgreement': True}}, 'adverseEventsModule': {'timeFrame': 'Deaths are reported from enrollment through to end of follow-up; median time on follow up was 108 weeks (2.7 to 245.6 weeks). Adverse events are reported from first dose through 30 days after last dose of talimogene laherparepvec; median duration of treatment was 25.143 (0.14 to 241.43 weeks)', 'description': 'All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.', 'eventGroups': [{'id': 'EG000', 'title': 'Talimogene Laherparepvec', 'description': 'Talimogene laherparepvec was administered by intralesional injection into injectable cutaneous, subcutaneous, and nodal lesions at an initial dose of 10⁶ plaque-forming units (PFU) per mL on day 1 followed by a dose of 10⁸ PFU/mL 21 days after the initial dose and every 14 days thereafter. Participants were treated with talimogene laherparepvec until they achieved a complete response, all injectable tumors had disappeared, clinically significant (resulting in clinical deterioration or requiring change of therapy) disease progression beyond 6 months of treatment, per modified World Health Organization (WHO) response criteria, or intolerance of study treatment, whichever occurred first.', 'otherNumAtRisk': 111, 'deathsNumAtRisk': 112, 'otherNumAffected': 97, 'seriousNumAtRisk': 111, 'deathsNumAffected': 41, 'seriousNumAffected': 33}], 'otherEvents': [{'term': 'Abdominal pain', 'stats': [{'groupId': 'EG000', 'numAtRisk': 111, 'numAffected': 7}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 23.1'}, {'term': 'Diarrhoea', 'stats': [{'groupId': 'EG000', 'numAtRisk': 111, 'numAffected': 14}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 23.1'}, {'term': 'Nausea', 'stats': [{'groupId': 'EG000', 'numAtRisk': 111, 'numAffected': 26}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 23.1'}, {'term': 'Vomiting', 'stats': [{'groupId': 'EG000', 'numAtRisk': 111, 'numAffected': 11}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 23.1'}, {'term': 'Asthenia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 111, 'numAffected': 18}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 23.1'}, {'term': 'Chills', 'stats': [{'groupId': 'EG000', 'numAtRisk': 111, 'numAffected': 30}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 23.1'}, {'term': 'Fatigue', 'stats': [{'groupId': 'EG000', 'numAtRisk': 111, 'numAffected': 24}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 23.1'}, {'term': 'Influenza like illness', 'stats': [{'groupId': 'EG000', 'numAtRisk': 111, 'numAffected': 29}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 23.1'}, {'term': 'Injection site pain', 'stats': [{'groupId': 'EG000', 'numAtRisk': 111, 'numAffected': 19}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 23.1'}, {'term': 'Pain', 'stats': [{'groupId': 'EG000', 'numAtRisk': 111, 'numAffected': 7}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 23.1'}, {'term': 'Pyrexia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 111, 'numAffected': 52}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 23.1'}, {'term': 'Decreased appetite', 'stats': [{'groupId': 'EG000', 'numAtRisk': 111, 'numAffected': 8}], 'organSystem': 'Metabolism and nutrition disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 23.1'}, {'term': 'Arthralgia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 111, 'numAffected': 20}], 'organSystem': 'Musculoskeletal and connective tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 23.1'}, {'term': 'Back pain', 'stats': [{'groupId': 'EG000', 'numAtRisk': 111, 'numAffected': 9}], 'organSystem': 'Musculoskeletal and connective tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 23.1'}, {'term': 'Pain in extremity', 'stats': [{'groupId': 'EG000', 'numAtRisk': 111, 'numAffected': 16}], 'organSystem': 'Musculoskeletal and connective tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 23.1'}, {'term': 'Headache', 'stats': [{'groupId': 'EG000', 'numAtRisk': 111, 'numAffected': 21}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 23.1'}, {'term': 'Cough', 'stats': [{'groupId': 'EG000', 'numAtRisk': 111, 'numAffected': 8}], 'organSystem': 'Respiratory, thoracic and mediastinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 23.1'}, {'term': 'Oedema peripheral', 'stats': [{'groupId': 'EG000', 'numAtRisk': 111, 'numAffected': 7}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 23.1'}, {'term': 'Nasopharyngitis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 111, 'numAffected': 11}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 23.1'}, {'term': 'Anaemia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 111, 'numAffected': 8}], 'organSystem': 'Blood and lymphatic system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 23.1'}, {'term': 'Erythema', 'stats': [{'groupId': 'EG000', 'numAtRisk': 111, 'numAffected': 6}], 'organSystem': 'Skin and subcutaneous tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 23.1'}], 'seriousEvents': [{'term': 'Cardiac failure', 'stats': [{'groupId': 'EG000', 'numAtRisk': 111, 'numAffected': 1}], 'organSystem': 'Cardiac disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 23.1'}, {'term': 'Cardio-respiratory arrest', 'stats': [{'groupId': 'EG000', 'numAtRisk': 111, 'numAffected': 1}], 'organSystem': 'Cardiac disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 23.1'}, {'term': 'Vertigo positional', 'stats': [{'groupId': 'EG000', 'numAtRisk': 111, 'numAffected': 1}], 'organSystem': 'Ear and labyrinth disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 23.1'}, {'term': 'Faecaloma', 'stats': [{'groupId': 'EG000', 'numAtRisk': 111, 'numAffected': 1}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 23.1'}, {'term': 'General physical health deterioration', 'stats': [{'groupId': 'EG000', 'numAtRisk': 111, 'numAffected': 2}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 23.1'}, {'term': 'Pyrexia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 111, 'numAffected': 2}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 23.1'}, {'term': 'Cholecystitis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 111, 'numAffected': 1}], 'organSystem': 'Hepatobiliary disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 23.1'}, {'term': 'Cytokine release syndrome', 'stats': [{'groupId': 'EG000', 'numAtRisk': 111, 'numAffected': 1}], 'organSystem': 'Immune system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 23.1'}, {'term': 'Bronchitis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 111, 'numAffected': 1}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 23.1'}, {'term': 'Pneumonia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 111, 'numAffected': 1}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 23.1'}, {'term': 'Fall', 'stats': [{'groupId': 'EG000', 'numAtRisk': 111, 'numAffected': 1}], 'organSystem': 'Injury, poisoning and procedural complications', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 23.1'}, {'term': 'Medical observation', 'stats': [{'groupId': 'EG000', 'numAtRisk': 111, 'numAffected': 1}], 'organSystem': 'Investigations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 23.1'}, {'term': 'Back pain', 'stats': [{'groupId': 'EG000', 'numAtRisk': 111, 'numAffected': 2}], 'organSystem': 'Musculoskeletal and connective tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 23.1'}, {'term': 'Pain in extremity', 'stats': [{'groupId': 'EG000', 'numAtRisk': 111, 'numAffected': 1}], 'organSystem': 'Musculoskeletal and connective tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 23.1'}, {'term': 'Bladder transitional cell carcinoma', 'stats': [{'groupId': 'EG000', 'numAtRisk': 111, 'numAffected': 1}], 'organSystem': 'Neoplasms benign, malignant and unspecified (incl cysts and polyps)', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 23.1'}, {'term': 'Metastases to central nervous system', 'stats': [{'groupId': 'EG000', 'numAtRisk': 111, 'numAffected': 2}], 'organSystem': 'Neoplasms benign, malignant and unspecified (incl cysts and polyps)', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 23.1'}, {'term': 'Metastases to lymph nodes', 'stats': [{'groupId': 'EG000', 'numAtRisk': 111, 'numAffected': 1}], 'organSystem': 'Neoplasms benign, malignant and unspecified (incl cysts and polyps)', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 23.1'}, {'term': 'Metastases to pleura', 'stats': [{'groupId': 'EG000', 'numAtRisk': 111, 'numAffected': 1}], 'organSystem': 'Neoplasms benign, malignant and unspecified (incl cysts and polyps)', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 23.1'}, {'term': 'Metastatic malignant melanoma', 'stats': [{'groupId': 'EG000', 'numAtRisk': 111, 'numAffected': 3}], 'organSystem': 'Neoplasms benign, malignant and unspecified (incl cysts and polyps)', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 23.1'}, {'term': 'Nodular melanoma', 'stats': [{'groupId': 'EG000', 'numAtRisk': 111, 'numAffected': 1}], 'organSystem': 'Neoplasms benign, malignant and unspecified (incl cysts and polyps)', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 23.1'}, {'term': 'Tumour haemorrhage', 'stats': [{'groupId': 'EG000', 'numAtRisk': 111, 'numAffected': 1}], 'organSystem': 'Neoplasms benign, malignant and unspecified (incl cysts and polyps)', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 23.1'}, {'term': 'Anxiety', 'stats': [{'groupId': 'EG000', 'numAtRisk': 111, 'numAffected': 1}], 'organSystem': 'Psychiatric disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 23.1'}, {'term': 'Paranoia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 111, 'numAffected': 1}], 'organSystem': 'Psychiatric disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 23.1'}, {'term': 'Haemoptysis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 111, 'numAffected': 1}], 'organSystem': 'Respiratory, thoracic and mediastinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 23.1'}, {'term': 'Pleural effusion', 'stats': [{'groupId': 'EG000', 'numAtRisk': 111, 'numAffected': 1}], 'organSystem': 'Respiratory, thoracic and mediastinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 23.1'}, {'term': 'Oedema peripheral', 'stats': [{'groupId': 'EG000', 'numAtRisk': 111, 'numAffected': 1}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 23.1'}, {'term': 'Neurofibrosarcoma', 'stats': [{'groupId': 'EG000', 'numAtRisk': 111, 'numAffected': 1}], 'organSystem': 'Neoplasms benign, malignant and unspecified (incl cysts and polyps)', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 23.1'}, {'term': 'Cardiac pacemaker replacement', 'stats': [{'groupId': 'EG000', 'numAtRisk': 111, 'numAffected': 1}], 'organSystem': 'Surgical and medical procedures', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 23.1'}, {'term': 'Anaemia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 111, 'numAffected': 1}], 'organSystem': 'Blood and lymphatic system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 23.1'}, {'term': 'Ileus', 'stats': [{'groupId': 'EG000', 'numAtRisk': 111, 'numAffected': 1}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 23.1'}, {'term': 'COVID-19 pneumonia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 111, 'numAffected': 1}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 23.1'}, {'term': 'Humerus fracture', 'stats': [{'groupId': 'EG000', 'numAtRisk': 111, 'numAffected': 1}], 'organSystem': 'Injury, poisoning and procedural complications', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 23.1'}, {'term': 'Meningioma', 'stats': [{'groupId': 'EG000', 'numAtRisk': 111, 'numAffected': 1}], 'organSystem': 'Neoplasms benign, malignant and unspecified (incl cysts and polyps)', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 23.1'}], 'frequencyThreshold': '5'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Odds Ratio of Baseline Intratumoral CD8+ Cell Density and Objective Response Rate', 'denoms': [{'units': 'Participants', 'counts': [{'value': '91', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Talimogene Laherparepvec', 'description': 'Talimogene laherparepvec was administered by intralesional injection into injectable cutaneous, subcutaneous, and nodal lesions at an initial dose of 10⁶ plaque-forming units (PFU) per mL on day 1 followed by a dose of 10⁸ PFU/mL 21 days after the initial dose and every 14 days thereafter. Participants were treated with talimogene laherparepvec until they achieved a complete response, all injectable tumors had disappeared, clinically significant (resulting in clinical deterioration or requiring change of therapy) disease progression beyond 6 months of treatment, per modified World Health Organization (WHO) response criteria, or intolerance of study treatment, whichever occurred first.'}], 'classes': [{'categories': [{'measurements': [{'value': '1.11', 'groupId': 'OG000', 'lowerLimit': '0.87', 'upperLimit': '1.42'}]}]}], 'analyses': [{'pValue': '0.387', 'groupIds': ['OG000'], 'statisticalMethod': 'Regression, Logistic', 'nonInferiorityType': 'OTHER'}], 'paramType': 'NUMBER', 'timeFrame': 'Intratumoral CD8+ cell density: Baseline. Response: every 12 weeks until disease progression beyond 6 months of treatment or the start of new anticancer therapy; median time on follow-up at primary completion = 59 weeks (min 3 to max 116 weeks)', 'description': 'A univariate logistic regression model was performed to evaluate baseline log2(CD8+ cell density) as a predictor of objective response.\n\nResponse was assessed according to the modified version of the World Health Organization (WHO) response criteria. Objective response rate (ORR) was defined as the percentage of participants with a complete response (CR) or partial response (PR) according to the modified WHO criteria.\n\nThe unadjusted odds ratio of log2(baseline intratumoral CD8+ cell density) for objective response rate is reported.', 'unitOfMeasure': 'ratio', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED', 'populationDescription': 'Participants who received at least 1 dose of talimogene laherparepvec with non-missing baseline CD8+ cell density data. Data is available for 91 participants who had data available for analysis at the time of primary completion (26 June 2017).'}, {'type': 'SECONDARY', 'title': 'Odds Ratio of Baseline Intratumoral CD8+ Cell Density and Durable Response Rate', 'denoms': [{'units': 'Participants', 'counts': [{'value': '93', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Talimogene Laherparepvec', 'description': 'Talimogene laherparepvec was administered by intralesional injection into injectable cutaneous, subcutaneous, and nodal lesions at an initial dose of 10⁶ plaque-forming units (PFU) per mL on day 1 followed by a dose of 10⁸ PFU/mL 21 days after the initial dose and every 14 days thereafter. Participants were treated with talimogene laherparepvec until they achieved a complete response, all injectable tumors had disappeared, clinically significant (resulting in clinical deterioration or requiring change of therapy) disease progression beyond 6 months of treatment, per modified World Health Organization (WHO) response criteria, or intolerance of study treatment, whichever occurred first.'}], 'classes': [{'title': 'Primary completion', 'denoms': [{'units': 'Participants', 'counts': [{'value': '91', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '1.40', 'groupId': 'OG000', 'lowerLimit': '0.99', 'upperLimit': '1.97'}]}]}, {'title': 'Final analysis', 'denoms': [{'units': 'Participants', 'counts': [{'value': '93', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '1.18', 'groupId': 'OG000', 'lowerLimit': '0.91', 'upperLimit': '1.53'}]}]}], 'analyses': [{'pValue': '0.056', 'groupIds': ['OG000'], 'statisticalMethod': 'Regression, Logistic', 'nonInferiorityType': 'OTHER', 'nonInferiorityComment': 'Primary completion data.'}, {'pValue': '0.222', 'groupIds': ['OG000'], 'statisticalMethod': 'Regression, Logistic', 'nonInferiorityType': 'OTHER', 'nonInferiorityComment': 'Final analysis data.'}], 'paramType': 'NUMBER', 'timeFrame': 'Intratumoral CD8+ cell density: Baseline. Response: every 12 weeks until disease progression beyond 6 months of treatment or the start of new anticancer therapy; median time on follow-up: PC: 59 weeks (3 to 116 weeks); FA: 108 weeks (2.7 to 245.6)', 'description': 'A univariate logistic regression model was performed to evaluate baseline log2(CD8+ cell density) as a predictor of durable response.\n\nResponse was assessed according to the modified version of the World Health Organization (WHO) response criteria. Durable response rate (DRR) was defined as the percentage of participants with an objective response lasting continuously for 6 months and starting any time within 12 months of initiating therapy.\n\nThe unadjusted odds ratio of log2(baseline intratumoral CD8+ cell density) for durable response rate is reported.\n\nPrimary completion is defined as PC and final analysis is defined as FA.', 'unitOfMeasure': 'ratio', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED', 'populationDescription': 'Participants who received at least 1 dose of talimogene laherparepvec with non-missing baseline CD8+ cell density data. Data is available for 91 participants who had data available for analysis at the time of primary completion (26 June 2017). Data is also presented for 93 participants who had data available at final analysis (25 December 2020).'}, {'type': 'SECONDARY', 'title': 'Hazards Ratio of Baseline Intratumoral CD8+ Cell Density and Duration of Response', 'denoms': [{'units': 'Participants', 'counts': [{'value': '29', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Talimogene Laherparepvec', 'description': 'Talimogene laherparepvec was administered by intralesional injection into injectable cutaneous, subcutaneous, and nodal lesions at an initial dose of 10⁶ plaque-forming units (PFU) per mL on day 1 followed by a dose of 10⁸ PFU/mL 21 days after the initial dose and every 14 days thereafter. Participants were treated with talimogene laherparepvec until they achieved a complete response, all injectable tumors had disappeared, clinically significant (resulting in clinical deterioration or requiring change of therapy) disease progression beyond 6 months of treatment, per modified World Health Organization (WHO) response criteria, or intolerance of study treatment, whichever occurred first.'}], 'classes': [{'title': 'Primary completion', 'denoms': [{'units': 'Participants', 'counts': [{'value': '27', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '0.74', 'groupId': 'OG000', 'lowerLimit': '0.39', 'upperLimit': '1.37'}]}]}, {'title': 'Final analysis', 'denoms': [{'units': 'Participants', 'counts': [{'value': '29', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '0.91', 'groupId': 'OG000', 'lowerLimit': '0.63', 'upperLimit': '1.30'}]}]}], 'analyses': [{'pValue': '0.335', 'groupIds': ['OG000'], 'statisticalMethod': 'Cox proportional hazards', 'nonInferiorityType': 'OTHER', 'nonInferiorityComment': 'Primary completion data'}, {'pValue': '0.597', 'groupIds': ['OG000'], 'statisticalMethod': 'Cox proportional hazards', 'nonInferiorityType': 'OTHER', 'nonInferiorityComment': 'Final analysis data'}], 'paramType': 'NUMBER', 'timeFrame': 'Intratumoral CD8+ cell density: Baseline. Response: every 12 weeks until disease progression beyond 6 months of treatment or the start of new anticancer therapy; median time on follow-up: PC: 59 weeks (3 to 116 weeks); FA: 108 weeks (2.7 to 245.6 weeks)', 'description': 'A Cox proportional hazards regression model was performed to evaluate baseline log2(CD8+ cell density) as a predictor of duration of response.\n\nResponse was assessed according to the modified version of the World Health Organization (WHO) response criteria. Duration of response (DOR) is defined as the longest individual period from entering an objective response (CR/PR) to the first documented evidence of the participant no longer meeting the criteria for being in the response (i.e. an overall response of either stable disease \\[SD\\] as compared with baseline or progressive disease \\[PD\\]).\n\nThe unadjusted hazard ratio of log2(baseline intratumoral CD8+ cell density) for duration of response is reported.', 'unitOfMeasure': 'ratio', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED', 'populationDescription': 'Participants who received at least 1 dose of talimogene laherparepvec with an objective response at the time of primary completion or final analysis, and with baseline CD8+ cell density data.'}, {'type': 'SECONDARY', 'title': 'Correlation Between Baseline Intratumoral CD8+ Cell Density and Changes in Tumor Burden', 'denoms': [{'units': 'Participants', 'counts': [{'value': '85', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Talimogene Laherparepvec', 'description': 'Talimogene laherparepvec was administered by intralesional injection into injectable cutaneous, subcutaneous, and nodal lesions at an initial dose of 10⁶ plaque-forming units (PFU) per mL on day 1 followed by a dose of 10⁸ PFU/mL 21 days after the initial dose and every 14 days thereafter. Participants were treated with talimogene laherparepvec until they achieved a complete response, all injectable tumors had disappeared, clinically significant (resulting in clinical deterioration or requiring change of therapy) disease progression beyond 6 months of treatment, per modified World Health Organization (WHO) response criteria, or intolerance of study treatment, whichever occurred first.'}], 'classes': [{'title': 'Primary completion', 'denoms': [{'units': 'Participants', 'counts': [{'value': '82', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '0.03', 'groupId': 'OG000', 'lowerLimit': '-0.19', 'upperLimit': '0.24'}]}]}, {'title': 'Final analysis', 'denoms': [{'units': 'Participants', 'counts': [{'value': '85', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '0.01', 'groupId': 'OG000', 'lowerLimit': '-0.20', 'upperLimit': '0.23'}]}]}], 'analyses': [{'pValue': '0.82', 'groupIds': ['OG000'], 'statisticalMethod': "Fisher's Z transformation", 'nonInferiorityType': 'OTHER', 'nonInferiorityComment': 'Primary completion'}, {'pValue': '0.90', 'groupIds': ['OG000'], 'statisticalMethod': "Fisher's Z transformation", 'nonInferiorityType': 'OTHER', 'nonInferiorityComment': 'Final analysis data'}], 'paramType': 'NUMBER', 'timeFrame': 'Intratumoral CD8+ cell density: Baseline; Tumor burden: First dose of study drug until primary completion date (26 June 2017) or end of follow-up; median time on follow-up: PC: 59 weeks (3 to 116 weeks); FA: 108 weeks (2.7 to 245.6 weeks)', 'description': "Pearson's correlation coefficient (r) was estimated to assess the relationship between baseline log2(CD8+ cell density) and the maximum decrease in measurable tumor burden.\n\nTumor burden is the sum of the products of the 2 largest perpendicular diameters (SPD) for all index lesions selected at baseline.\n\nThe Pearson's correlation coefficient (r) of log2(baseline intratumoral CD8+ cell density) and the maximum decrease in tumor burden is reported.\n\nPrimary completion is defined as PC and final analysis is defined as FA.", 'unitOfMeasure': "Pearson's correlation coefficient", 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED', 'populationDescription': 'Participants who received at least 1 dose of talimogene laherparepvec with available tumor burden data at primary completion or final analysis, and baseline CD8+ cell density data.'}, {'type': 'SECONDARY', 'title': 'Odds Ratio of Change From Baseline Intratumoral CD8+ Cell Density and Objective Response Rate', 'denoms': [{'units': 'Participants', 'counts': [{'value': '63', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Talimogene Laherparepvec', 'description': 'Talimogene laherparepvec was administered by intralesional injection into injectable cutaneous, subcutaneous, and nodal lesions at an initial dose of 10⁶ plaque-forming units (PFU) per mL on day 1 followed by a dose of 10⁸ PFU/mL 21 days after the initial dose and every 14 days thereafter. Participants were treated with talimogene laherparepvec until they achieved a complete response, all injectable tumors had disappeared, clinically significant (resulting in clinical deterioration or requiring change of therapy) disease progression beyond 6 months of treatment, per modified World Health Organization (WHO) response criteria, or intolerance of study treatment, whichever occurred first.'}], 'classes': [{'title': 'Primary completion', 'denoms': [{'units': 'Participants', 'counts': [{'value': '59', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '0.94', 'groupId': 'OG000', 'lowerLimit': '0.72', 'upperLimit': '1.24'}]}]}, {'title': 'Final analysis', 'denoms': [{'units': 'Participants', 'counts': [{'value': '63', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '0.98', 'groupId': 'OG000', 'lowerLimit': '0.76', 'upperLimit': '1.27'}]}]}], 'analyses': [{'pValue': '0.660', 'groupIds': ['OG000'], 'statisticalMethod': 'Regression, Logistic', 'nonInferiorityType': 'OTHER', 'nonInferiorityComment': 'Primary completion data'}, {'pValue': '0.881', 'groupIds': ['OG000'], 'statisticalMethod': 'Regression, Logistic', 'nonInferiorityType': 'OTHER', 'nonInferiorityComment': 'Final analysis data'}], 'paramType': 'NUMBER', 'timeFrame': 'CD8+ cell density: Baseline & Week 6. Response: every 12 weeks until disease progression beyond 6 months of treatment or the start of new anticancer therapy; median time on follow-up: PC: 59 weeks (3 to 116 weeks); FA: 108 weeks (2.7 to 245.6 weeks)', 'description': 'A univariate logistic regression model was performed to evaluate change from baseline to week 6 in log2(CD8+ cell density) in uninjected tumors as a predictor of objective response.\n\nResponse was assessed according to the modified version of the World Health Organization (WHO) response criteria. Objective response rate (ORR) was defined as the percentage of participants with a complete response or partial response according to the modified WHO criteria.\n\nThe unadjusted odds ratio of log2(change from baseline intratumoral CD8+ cell density) for objective response rate is reported.\n\nIntratumoral CD8+ Cell density has been shortened to "CD8+ cell density" in the time frame due to character limit. Primary completion is defined as PC and final analysis is defined as FA.', 'unitOfMeasure': 'ratio', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED', 'populationDescription': 'Participants who received at least 1 dose of talimogene laherparepvec with baseline and week 6 CD8+ cell density data for uninjected lesions. Data is available for 59 participants who had data available for analysis at the time of primary completion (26 June 2017). Data is also presented for 63 participants who had data available at final analysis (25 December 2020).'}, {'type': 'SECONDARY', 'title': 'Odds Ratio of Change From Baseline in Intratumoral CD8+ Cell Density and Durable Response Rate', 'denoms': [{'units': 'Participants', 'counts': [{'value': '63', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Talimogene Laherparepvec', 'description': 'Talimogene laherparepvec was administered by intralesional injection into injectable cutaneous, subcutaneous, and nodal lesions at an initial dose of 10⁶ plaque-forming units (PFU) per mL on day 1 followed by a dose of 10⁸ PFU/mL 21 days after the initial dose and every 14 days thereafter. Participants were treated with talimogene laherparepvec until they achieved a complete response, all injectable tumors had disappeared, clinically significant (resulting in clinical deterioration or requiring change of therapy) disease progression beyond 6 months of treatment, per modified World Health Organization (WHO) response criteria, or intolerance of study treatment, whichever occurred first.'}], 'classes': [{'title': 'Primary completion', 'denoms': [{'units': 'Participants', 'counts': [{'value': '59', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '0.99', 'groupId': 'OG000', 'lowerLimit': '0.69', 'upperLimit': '1.44'}]}]}, {'title': 'Final analysis', 'denoms': [{'units': 'Participants', 'counts': [{'value': '63', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '0.93', 'groupId': 'OG000', 'lowerLimit': '0.68', 'upperLimit': '1.25'}]}]}], 'analyses': [{'pValue': '0.974', 'groupIds': ['OG000'], 'statisticalMethod': 'Regression, Logistic', 'nonInferiorityType': 'OTHER', 'nonInferiorityComment': 'Primary completion data'}, {'pValue': '0.612', 'groupIds': ['OG000'], 'statisticalMethod': 'Regression, Logistic', 'nonInferiorityType': 'OTHER', 'nonInferiorityComment': 'Final analysis data'}], 'paramType': 'NUMBER', 'timeFrame': 'CD8+ cell density: Baseline & Week 6. Response: every 12 weeks until disease progression beyond 6 months of treatment or the start of new anticancer therapy; median time on follow-up: PC: 59 weeks (3 to 116 weeks); FA: 108 weeks (2.7 to 245.6 weeks)', 'description': 'A univariate logistic regression model was performed to evaluate change from baseline to week 6 in log2(CD8+ cell density) in uninjected lesions as a predictor of durable response.\n\nResponse was assessed according to the modified version of the World Health Organization (WHO) response criteria. Durable response rate (DRR) was defined as the percentage of participants with an objective response lasting continuously for 6 months and starting any time within 12 months of initiating therapy.\n\nThe unadjusted odds ratio of log2(change from baseline in intratumoral CD8+ cell density) for durable response rate is reported.\n\nIntratumoral CD8+ Cell density has been shortened to "CD8+ cell density" in the time frame due to character limit. Primary completion is defined as PC and final analysis is defined as FA.', 'unitOfMeasure': 'ratio', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED', 'populationDescription': 'Participants who received at least 1 dose of talimogene laherparepvec with baseline and week 6 CD8+ cell density data in uninjected lesions. Data is available for 59 participants who had data available for analysis at the time of primary completion (26 June 2017). Data is also presented for 63 participants who had data available at final analysis (25 December 2020).'}, {'type': 'SECONDARY', 'title': 'Hazard Ratio of Change From Baseline in Intratumoral CD8+ Cell Density and Duration of Response', 'denoms': [{'units': 'Participants', 'counts': [{'value': '18', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Talimogene Laherparepvec', 'description': 'Talimogene laherparepvec was administered by intralesional injection into injectable cutaneous, subcutaneous, and nodal lesions at an initial dose of 10⁶ plaque-forming units (PFU) per mL on day 1 followed by a dose of 10⁸ PFU/mL 21 days after the initial dose and every 14 days thereafter. Participants were treated with talimogene laherparepvec until they achieved a complete response, all injectable tumors had disappeared, clinically significant (resulting in clinical deterioration or requiring change of therapy) disease progression beyond 6 months of treatment, per modified World Health Organization (WHO) response criteria, or intolerance of study treatment, whichever occurred first.'}], 'classes': [{'title': 'Primary completion', 'denoms': [{'units': 'Participants', 'counts': [{'value': '16', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '1.28', 'groupId': 'OG000', 'lowerLimit': '0.47', 'upperLimit': '3.47'}]}]}, {'title': 'Final analysis', 'denoms': [{'units': 'Participants', 'counts': [{'value': '18', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '1.12', 'groupId': 'OG000', 'lowerLimit': '0.74', 'upperLimit': '1.69'}]}]}], 'analyses': [{'pValue': '0.626', 'groupIds': ['OG000'], 'statisticalMethod': 'Cox proportional hazards', 'nonInferiorityType': 'OTHER', 'nonInferiorityComment': 'Primary completion data'}, {'pValue': '0.579', 'groupIds': ['OG000'], 'statisticalMethod': 'Cox proportional hazards', 'nonInferiorityType': 'OTHER', 'nonInferiorityComment': 'Final analysis data'}], 'paramType': 'NUMBER', 'timeFrame': 'CD8+ cell density: Baseline & Week 6. Response: every 12 weeks until disease progression beyond 6 months of treatment or the start of new anticancer therapy; median time on follow-up: PC: 59 weeks (3 to 116 weeks); FA: 108 weeks (2.7 to 245.6 weeks)', 'description': 'A Cox proportional hazards regression model was performed to evaluate change from baseline in log2(CD8+ cell density) as a predictor of duration of response.\n\nResponse was assessed according to the modified version of the World Health Organization (WHO) response criteria. Duration of response (DOR) is defined as the longest individual period from entering an objective response (CR/PR) to the first documented evidence of the participant no longer meeting the criteria for being in the response (i.e. an overall response of either stable disease \\[SD\\] as compared with baseline or progressive disease \\[PD\\]).\n\nThe unadjusted hazard ratio of log2(change from baseline intratumoral CD8+ cell density) for duration of response is reported.\n\nIntratumoral CD8+ Cell density has been shortened to "CD8+ cell density" in the time frame due to character limit. Primary completion is defined as PC and final analysis is defined as FA.', 'unitOfMeasure': 'ratio', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED', 'populationDescription': 'Participants who received at least 1 dose of talimogene laherparepvec with an objective response at either primary completion or final analysis, and with baseline and week 6 CD8+ cell density data for uninjected lesions.'}, {'type': 'SECONDARY', 'title': 'Correlation Between Change From Baseline in Intratumoral CD8+ Cell Density and Changes in Tumor Burden', 'denoms': [{'units': 'Participants', 'counts': [{'value': '60', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Talimogene Laherparepvec', 'description': 'Talimogene laherparepvec was administered by intralesional injection into injectable cutaneous, subcutaneous, and nodal lesions at an initial dose of 10⁶ plaque-forming units (PFU) per mL on day 1 followed by a dose of 10⁸ PFU/mL 21 days after the initial dose and every 14 days thereafter. Participants were treated with talimogene laherparepvec until they achieved a complete response, all injectable tumors had disappeared, clinically significant (resulting in clinical deterioration or requiring change of therapy) disease progression beyond 6 months of treatment, per modified World Health Organization (WHO) response criteria, or intolerance of study treatment, whichever occurred first.'}], 'classes': [{'title': 'Primary completion', 'denoms': [{'units': 'Participants', 'counts': [{'value': '56', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '-0.18', 'groupId': 'OG000', 'lowerLimit': '-0.42', 'upperLimit': '0.09'}]}]}, {'title': 'Final analysis', 'denoms': [{'units': 'Participants', 'counts': [{'value': '60', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '-0.19', 'groupId': 'OG000', 'lowerLimit': '-0.43', 'upperLimit': '0.06'}]}]}], 'analyses': [{'pValue': '0.18', 'groupIds': ['OG000'], 'statisticalMethod': "Pearson's correlation coefficient", 'nonInferiorityType': 'OTHER', 'nonInferiorityComment': 'Primary completion data'}, {'pValue': '0.14', 'groupIds': ['OG000'], 'statisticalMethod': "Pearson's correlation coefficient", 'nonInferiorityType': 'OTHER', 'nonInferiorityComment': 'Final analysis data'}], 'paramType': 'NUMBER', 'timeFrame': 'CD8+ cell density: Baseline & Week 6. Response: every 12 weeks until disease progression beyond 6 months of treatment or the start of new anticancer therapy; median time on follow-up: PC: 59 weeks (3 to 116 weeks); FA: 108 weeks (2.7 to 245.6 weeks)', 'description': 'Pearson\'s correlation coefficient (r) was estimated to assess the relationship between change from baseline in log2(CD8+ cell density) in uninjected lesions and the maximum decrease in measurable tumor burden.\n\nTumor burden is the sum of the products of the 2 largest perpendicular diameters (SPD) for all index lesions selected at baseline.\n\nThe Pearson\'s correlation coefficient (r) of log2(change from baseline intratumoral CD8+ cell density) and the maximum decrease in tumor burden is reported.\n\nIntratumoral CD8+ Cell density has been shortened to "CD8+ cell density" in the time frame due to character limit. Primary completion is defined as PC and final analysis is defined as FA.', 'unitOfMeasure': "Pearson's correlation coefficient", 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED', 'populationDescription': 'Participants who received at least 1 dose of talimogene laherparepvec with available tumor burden data at primary completion or final analysis, and baseline and week 6 CD8+ cell density data for uninjected lesions.'}, {'type': 'SECONDARY', 'title': 'Objective Response Rate', 'denoms': [{'units': 'Participants', 'counts': [{'value': '111', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Talimogene Laherparepvec', 'description': 'Talimogene laherparepvec was administered by intralesional injection into injectable cutaneous, subcutaneous, and nodal lesions at an initial dose of 10⁶ plaque-forming units (PFU) per mL on day 1 followed by a dose of 10⁸ PFU/mL 21 days after the initial dose and every 14 days thereafter. Participants were treated with talimogene laherparepvec until they achieved a complete response, all injectable tumors had disappeared, clinically significant (resulting in clinical deterioration or requiring change of therapy) disease progression beyond 6 months of treatment, per modified World Health Organization (WHO) response criteria, or intolerance of study treatment, whichever occurred first.'}], 'classes': [{'title': 'Primary completion', 'categories': [{'measurements': [{'value': '27.0', 'groupId': 'OG000', 'lowerLimit': '19.0', 'upperLimit': '36.3'}]}]}, {'title': 'Final analysis', 'categories': [{'measurements': [{'value': '28.8', 'groupId': 'OG000', 'lowerLimit': '20.6', 'upperLimit': '38.2'}]}]}], 'paramType': 'NUMBER', 'timeFrame': 'Response was assessed every 12 weeks until PD beyond 6 months of treatment or the start of new anticancer therapy; median time on follow-up at time of primary completion: 59 weeks (3 to 116 weeks); final analysis: 108 weeks (2.7 to 245.6 weeks)', 'description': 'Objective Response rate is defined as the percentage of participants with either a CR or PR based on Modified WHO Response Criteria.\n\nCR: Complete disappearance of all index lesions, all non-index lesions, and any new tumors which might have appeared. Any residual cutaneous or subcutaneous index lesions must be documented by representative biopsy to not contain viable tumor.\n\nPR: Disappearance of all index lesions with persistence of one or more non-index tumor(s), or, 50% or greater reduction in the 2 largest perpendicular diameters (SPD) of all index lesions as compared to baseline, and disappearance or persistence of non-index lesions.', 'unitOfMeasure': 'percentage of participants', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED', 'populationDescription': 'All participants who received at least 1 dose of talimogene laherparepvec.'}, {'type': 'SECONDARY', 'title': 'Duration of Response', 'denoms': [{'units': 'Participants', 'counts': [{'value': '32', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Talimogene Laherparepvec', 'description': 'Talimogene laherparepvec was administered by intralesional injection into injectable cutaneous, subcutaneous, and nodal lesions at an initial dose of 10⁶ plaque-forming units (PFU) per mL on day 1 followed by a dose of 10⁸ PFU/mL 21 days after the initial dose and every 14 days thereafter. Participants were treated with talimogene laherparepvec until they achieved a complete response, all injectable tumors had disappeared, clinically significant (resulting in clinical deterioration or requiring change of therapy) disease progression beyond 6 months of treatment, per modified World Health Organization (WHO) response criteria, or intolerance of study treatment, whichever occurred first.'}], 'classes': [{'title': 'Primary completion', 'denoms': [{'units': 'Participants', 'counts': [{'value': '30', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': 'NA', 'comment': 'Not reached at time of analysis as most participants were still in response.', 'groupId': 'OG000', 'lowerLimit': '11.5', 'upperLimit': 'NA'}]}]}, {'title': 'Final analysis', 'denoms': [{'units': 'Participants', 'counts': [{'value': '32', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': 'NA', 'comment': 'Not reached at time of analysis as most participants were still in response.', 'groupId': 'OG000', 'lowerLimit': '14.1', 'upperLimit': 'NA'}]}]}], 'paramType': 'MEDIAN', 'timeFrame': 'Response was assessed every 12 weeks until PD beyond 6 months of treatment or the start of new anticancer therapy; median time on follow-up at time of primary completion: 59 weeks (3 to 116 weeks); final analysis: 108 weeks (2.7 to 245.6 weeks)', 'description': 'Duration of response (DOR) was defined as the longest individual period from entering an objective response (CR/PR) to the first documented evidence of the participant no longer meeting the criteria for objective response (i.e. an overall response of either stable disease \\[SD\\] as compared with baseline or progressive disease \\[PD\\]).\n\nSD: Neither sufficient tumor shrinkage of index lesion to qualify for response (PR or CR) nor sufficient tumor increase of index lesion to qualify for PD, with no increase in size of non-index lesions.\n\nPD: A \\> 25% increase in the sum of the SPD of all index tumors since baseline, or the unequivocal appearance of a new tumor since the last response assessment time point, or unequivocal progression of one or more non-index lesions.\n\nParticipants last reported to be either a CR or PR were censored at that time point.', 'unitOfMeasure': 'months', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED', 'populationDescription': 'Participants who received at least 1 dose of talimogene laherparepvec with an objective response at either primary completion (26 June 2017) or final analysis (25 December 2020).'}, {'type': 'SECONDARY', 'title': 'Time to Treatment Failure', 'denoms': [{'units': 'Participants', 'counts': [{'value': '111', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Talimogene Laherparepvec', 'description': 'Talimogene laherparepvec was administered by intralesional injection into injectable cutaneous, subcutaneous, and nodal lesions at an initial dose of 10⁶ plaque-forming units (PFU) per mL on day 1 followed by a dose of 10⁸ PFU/mL 21 days after the initial dose and every 14 days thereafter. Participants were treated with talimogene laherparepvec until they achieved a complete response, all injectable tumors had disappeared, clinically significant (resulting in clinical deterioration or requiring change of therapy) disease progression beyond 6 months of treatment, per modified World Health Organization (WHO) response criteria, or intolerance of study treatment, whichever occurred first.'}], 'classes': [{'title': 'Primary completion', 'categories': [{'measurements': [{'value': '8.1', 'groupId': 'OG000', 'lowerLimit': '5.4', 'upperLimit': '10.9'}]}]}, {'title': 'Final analysis', 'categories': [{'measurements': [{'value': '8.1', 'groupId': 'OG000', 'lowerLimit': '5.4', 'upperLimit': '11.0'}]}]}], 'paramType': 'MEDIAN', 'timeFrame': 'From first dose of study drug until primary completion date of 26 June 2017, or end of follow-up; median time on follow-up at primary completion was 59 weeks (3 to 116 weeks); final analysis was 108 weeks (2.7 to 245.6 weeks)', 'description': 'Time to treatment failure (TTF) was calculated from first dosing until one or more of the following: (1) clinically relevant disease progression (PDr); (2) death from any cause; (3) non clinically relevant disease progression (PDn) associated with a requirement for alternative therapy as the reason for ending treatment or start of new anti-cancer therapy. Participants with no event were censored at their last evaluable tumor assessment.', 'unitOfMeasure': 'months', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED', 'populationDescription': 'Participants who received at least 1 dose of talimogene laherparepvec.'}, {'type': 'SECONDARY', 'title': 'Durable Response Rate', 'denoms': [{'units': 'Participants', 'counts': [{'value': '111', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Talimogene Laherparepvec', 'description': 'Talimogene laherparepvec was administered by intralesional injection into injectable cutaneous, subcutaneous, and nodal lesions at an initial dose of 10⁶ plaque-forming units (PFU) per mL on day 1 followed by a dose of 10⁸ PFU/mL 21 days after the initial dose and every 14 days thereafter. Participants were treated with talimogene laherparepvec until they achieved a complete response, all injectable tumors had disappeared, clinically significant (resulting in clinical deterioration or requiring change of therapy) disease progression beyond 6 months of treatment, per modified World Health Organization (WHO) response criteria, or intolerance of study treatment, whichever occurred first.'}], 'classes': [{'title': 'Primary completion', 'categories': [{'measurements': [{'value': '13.5', 'groupId': 'OG000', 'lowerLimit': '7.8', 'upperLimit': '21.3'}]}]}, {'title': 'Final analysis', 'categories': [{'measurements': [{'value': '21.6', 'groupId': 'OG000', 'lowerLimit': '14.4', 'upperLimit': '30.4'}]}]}], 'paramType': 'NUMBER', 'timeFrame': 'Response was assessed every 12 weeks until PD beyond 6 months of treatment or the start of new anticancer therapy; median time on follow-up at time of primary completion: 59 weeks (3 to 116 weeks); final analysis: 108 weeks (2.7 to 245.6 weeks)', 'description': 'Durable response rate (DRR) was defined as the percentage of participants with an objective response (CR or PR) based on modified WHO response criteria lasting continuously for 6 months and starting any time within 12 months of initiating therapy.', 'unitOfMeasure': 'percentage of participants', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED', 'populationDescription': 'Participants who received at least 1 dose of talimogene laherparepvec.'}, {'type': 'SECONDARY', 'title': 'Overall Survival', 'denoms': [{'units': 'Participants', 'counts': [{'value': '111', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Talimogene Laherparepvec', 'description': 'Talimogene laherparepvec was administered by intralesional injection into injectable cutaneous, subcutaneous, and nodal lesions at an initial dose of 10⁶ plaque-forming units (PFU) per mL on day 1 followed by a dose of 10⁸ PFU/mL 21 days after the initial dose and every 14 days thereafter. Participants were treated with talimogene laherparepvec until they achieved a complete response, all injectable tumors had disappeared, clinically significant (resulting in clinical deterioration or requiring change of therapy) disease progression beyond 6 months of treatment, per modified World Health Organization (WHO) response criteria, or intolerance of study treatment, whichever occurred first.'}], 'classes': [{'title': 'Primary completion', 'categories': [{'measurements': [{'value': 'NA', 'comment': 'Median overall survival was not reached due to the low number of deaths.', 'groupId': 'OG000', 'lowerLimit': 'NA', 'upperLimit': 'NA'}]}]}, {'title': 'Final analysis', 'categories': [{'measurements': [{'value': 'NA', 'comment': 'Median overall survival was not reached due to the low number of deaths.', 'groupId': 'OG000', 'lowerLimit': '34.9', 'upperLimit': 'NA'}]}]}], 'paramType': 'MEDIAN', 'timeFrame': 'From first dose of study drug until primary completion date of 26 June 2017, or end of follow-up; median time on follow-up at primary completion was 59 weeks (3 to 116 weeks); final analysis was 108 weeks (2.7 to 245.6 weeks)', 'description': 'Overall survival (OS) was defined as the time from the date of first dose to the date of death from any cause.\n\nOS time was censored at the last date the participant was known to be alive when the confirmation of death is absent or unknown.', 'unitOfMeasure': 'months', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED', 'populationDescription': 'Participants who received at least 1 dose of talimogene laherparepvec.'}, {'type': 'SECONDARY', 'title': 'Change From Baseline in Tumor Burden', 'denoms': [{'units': 'Participants', 'counts': [{'value': '32', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Talimogene Laherparepvec', 'description': 'Talimogene laherparepvec was administered by intralesional injection into injectable cutaneous, subcutaneous, and nodal lesions at an initial dose of 10⁶ plaque-forming units (PFU) per mL on day 1 followed by a dose of 10⁸ PFU/mL 21 days after the initial dose and every 14 days thereafter. Participants were treated with talimogene laherparepvec until they achieved a complete response, all injectable tumors had disappeared, clinically significant (resulting in clinical deterioration or requiring change of therapy) disease progression beyond 6 months of treatment, per modified World Health Organization (WHO) response criteria, or intolerance of study treatment, whichever occurred first.'}], 'classes': [{'title': 'Baseline', 'denoms': [{'units': 'Participants', 'counts': [{'value': '32', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '16.420', 'spread': '41.269', 'groupId': 'OG000'}]}]}, {'title': 'Change from baseline at Cycle 6 day 1', 'denoms': [{'units': 'Participants', 'counts': [{'value': '32', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '-5.883', 'spread': '12.158', 'groupId': 'OG000'}]}]}, {'title': 'Change from baseline at Cycle 12 day 1', 'denoms': [{'units': 'Participants', 'counts': [{'value': '30', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '-10.085', 'spread': '22.862', 'groupId': 'OG000'}]}]}, {'title': 'Change from baseline at Cycle 18 day 1', 'denoms': [{'units': 'Participants', 'counts': [{'value': '23', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '-13.074', 'spread': '27.798', 'groupId': 'OG000'}]}]}, {'title': 'Change from baseline at Cycle 24 day 1', 'denoms': [{'units': 'Participants', 'counts': [{'value': '15', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '-21.407', 'spread': '42.221', 'groupId': 'OG000'}]}]}, {'title': 'Change from baseline at Cycle 30 day 1', 'denoms': [{'units': 'Participants', 'counts': [{'value': '12', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '-30.404', 'spread': '55.593', 'groupId': 'OG000'}]}]}, {'title': 'Change from baseline at Cycle 36 day 1', 'denoms': [{'units': 'Participants', 'counts': [{'value': '10', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '-31.803', 'spread': '69.358', 'groupId': 'OG000'}]}]}, {'title': 'Change from baseline at Cycle 42 day 1', 'denoms': [{'units': 'Participants', 'counts': [{'value': '9', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '-10.208', 'spread': '14.188', 'groupId': 'OG000'}]}]}, {'title': 'Change from baseline at Cycle 48 day 1', 'denoms': [{'units': 'Participants', 'counts': [{'value': '8', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '-11.396', 'spread': '14.885', 'groupId': 'OG000'}]}]}, {'title': 'Change from baseline at Cycle 54 day 1', 'denoms': [{'units': 'Participants', 'counts': [{'value': '8', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '-11.693', 'spread': '15.720', 'groupId': 'OG000'}]}]}, {'title': 'Change from baseline at Cycle 60 day 1', 'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '-13.122', 'spread': '17.791', 'groupId': 'OG000'}]}]}, {'title': 'Change from baseline at Cycle 66 day 1', 'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '-16.797', 'spread': '14.659', 'groupId': 'OG000'}]}]}, {'title': 'Change from baseline at Cycle 72 day 1', 'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '-16.797', 'spread': '14.659', 'groupId': 'OG000'}]}]}, {'title': 'Change from baseline at Cycle 78 day 1', 'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '-16.858', 'spread': '14.730', 'groupId': 'OG000'}]}]}, {'title': 'Change from baseline at Cycle 84 day 1', 'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '-17.022', 'spread': '14.992', 'groupId': 'OG000'}]}]}, {'title': 'Change from baseline at Cycle 90 day 1', 'denoms': [{'units': 'Participants', 'counts': [{'value': '5', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '-13.916', 'spread': '14.381', 'groupId': 'OG000'}]}]}, {'title': 'Change from baseline at Cycle 96 day 1', 'denoms': [{'units': 'Participants', 'counts': [{'value': '4', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '-16.505', 'spread': '15.244', 'groupId': 'OG000'}]}]}, {'title': 'Change from baseline at Cycle 102 day 1', 'denoms': [{'units': 'Participants', 'counts': [{'value': '3', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '-17.793', 'spread': '18.413', 'groupId': 'OG000'}]}]}, {'title': 'Change from baseline at Cycle 108 day 1', 'denoms': [{'units': 'Participants', 'counts': [{'value': '3', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '-17.733', 'spread': '18.426', 'groupId': 'OG000'}]}]}, {'title': 'Change from baseline at Cycle 114 day 1', 'denoms': [{'units': 'Participants', 'counts': [{'value': '1', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '-1.694', 'spread': 'NA', 'comment': 'Only 1 participant had non-missing data at this time-point, so standard deviation could not be calculated.', 'groupId': 'OG000'}]}]}, {'title': 'Change from baseline at Cycle 120 day 1', 'denoms': [{'units': 'Participants', 'counts': [{'value': '1', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '-39.930', 'spread': 'NA', 'comment': 'Only 1 participant had non-missing data at this time-point, so standard deviation could not be calculated.', 'groupId': 'OG000'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'Baseline and Day 1 of cycle 6, 12 , 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, 96, 102, 108, 114, and 120. The first cycle was 21 days and all subsequent cycles were 14 days.', 'description': 'Tumor burden is the sum of the products of the 2 largest perpendicular diameters (SPD) for all index lesions selected at baseline.\n\nChange from baseline in tumor burden was assessed in participants with an objective response.', 'unitOfMeasure': 'cm²', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'Participants who received at least 1 dose of talimogene laherparepvec with an objective response (CR or PR)'}, {'type': 'SECONDARY', 'title': 'Number of Participants With Adverse Events', 'denoms': [{'units': 'Participants', 'counts': [{'value': '111', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Talimogene Laherparepvec', 'description': 'Talimogene laherparepvec was administered by intralesional injection into injectable cutaneous, subcutaneous, and nodal lesions at an initial dose of 10⁶ plaque-forming units (PFU) per mL on day 1 followed by a dose of 10⁸ PFU/mL 21 days after the initial dose and every 14 days thereafter. Participants were treated with talimogene laherparepvec until they achieved a complete response, all injectable tumors had disappeared, clinically significant (resulting in clinical deterioration or requiring change of therapy) disease progression beyond 6 months of treatment, per modified World Health Organization (WHO) response criteria, or intolerance of study treatment, whichever occurred first.'}], 'classes': [{'title': 'Any adverse event', 'categories': [{'measurements': [{'value': '108', 'groupId': 'OG000'}]}]}, {'title': 'Adverse events ≥ grade 3', 'categories': [{'measurements': [{'value': '38', 'groupId': 'OG000'}]}]}, {'title': 'Adverse events ≥ grade 4', 'categories': [{'measurements': [{'value': '11', 'groupId': 'OG000'}]}]}, {'title': 'Serious adverse events', 'categories': [{'measurements': [{'value': '33', 'groupId': 'OG000'}]}]}, {'title': 'AE leading to discontinuation of study drug', 'categories': [{'measurements': [{'value': '4', 'groupId': 'OG000'}]}]}, {'title': 'Fatal adverse events', 'categories': [{'measurements': [{'value': '4', 'groupId': 'OG000'}]}]}, {'title': 'Treatment-related adverse events', 'categories': [{'measurements': [{'value': '93', 'groupId': 'OG000'}]}]}, {'title': 'Treatment-related adverse events ≥ grade 3', 'categories': [{'measurements': [{'value': '11', 'groupId': 'OG000'}]}]}, {'title': 'Treatment-related adverse events ≥ grade 4', 'categories': [{'measurements': [{'value': '2', 'groupId': 'OG000'}]}]}, {'title': 'Treatment-related serious adverse events', 'categories': [{'measurements': [{'value': '9', 'groupId': 'OG000'}]}]}, {'title': 'TRAE leading to discontinuation of study drug', 'categories': [{'measurements': [{'value': '3', 'groupId': 'OG000'}]}]}, {'title': 'Treatment-related fatal adverse events', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': 'From first dose through 30 days after last dose of talimogene laherparepvec; median duration of treatment was 25.143 weeks (range 0.14 to 241.43 weeks)', 'description': 'The severity of each adverse event (AE) was assessed according to the Common Terminology Criteria for Adverse Events (CTCAE), version 3.0 grading scale, where Grade 1 = Mild AE Grade 2 = Moderate AE Grade 3 = Severe AE Grade 4 = Life-threatening or disabling AE Grade 5 = Death related to AE Treatment-related adverse events (TRAE) were those assessed by the investigator as possibly related to talimogene laherparepvec.', 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED', 'populationDescription': 'Participants who received at least 1 dose of talimogene laherparepvec.'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'Talimogene Laherparepvec', 'description': 'Talimogene laherparepvec was administered by intralesional injection into injectable cutaneous, subcutaneous, and nodal lesions at an initial dose of 10⁶ plaque-forming units (PFU) per mL on day 1 followed by a dose of 10⁸ PFU/mL 21 days after the initial dose and every 14 days thereafter. Participants were treated with talimogene laherparepvec until they achieved a complete response, all injectable tumors had disappeared, clinically significant (resulting in clinical deterioration or requiring change of therapy) disease progression beyond 6 months of treatment, per modified World Health Organization (WHO) response criteria, or intolerance of study treatment, whichever occurred first.'}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '112'}]}, {'type': 'Received Study Drug', 'achievements': [{'groupId': 'FG000', 'numSubjects': '111'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '58'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '54'}]}], 'dropWithdraws': [{'type': 'Protocol-specified criteria', 'reasons': [{'groupId': 'FG000', 'numSubjects': '3'}]}, {'type': 'Withdrawal by Subject', 'reasons': [{'groupId': 'FG000', 'numSubjects': '9'}]}, {'type': 'Lost to Follow-up', 'reasons': [{'groupId': 'FG000', 'numSubjects': '1'}]}, {'type': 'Death', 'reasons': [{'groupId': 'FG000', 'numSubjects': '41'}]}]}], 'recruitmentDetails': 'This study was conducted at 36 centers across 12 countries in Europe from 07 April 2015 to 25 December 2020.'}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '111', 'groupId': 'BG000'}]}], 'groups': [{'id': 'BG000', 'title': 'Talimogene Laherparepvec', 'description': 'Talimogene laherparepvec was administered by intralesional injection into injectable cutaneous, subcutaneous, and nodal lesions at an initial dose of 10⁶ plaque-forming units (PFU) per mL on day 1 followed by a dose of 10⁸ PFU/mL 21 days after the initial dose and every 14 days thereafter. Participants were treated with talimogene laherparepvec until they achieved a complete response, all injectable tumors had disappeared, clinically significant (resulting in clinical deterioration or requiring change of therapy) disease progression beyond 6 months of treatment, per modified World Health Organization (WHO) response criteria, or intolerance of study treatment, whichever occurred first.'}], 'measures': [{'title': 'Age, Continuous', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '111', 'groupId': 'BG000'}]}], 'categories': [{'measurements': [{'value': '65.7', 'spread': '15.1', 'groupId': 'BG000'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'years', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Sex: Female, Male', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '111', 'groupId': 'BG000'}]}], 'categories': [{'title': 'Female', 'measurements': [{'value': '62', 'groupId': 'BG000'}]}, {'title': 'Male', 'measurements': [{'value': '49', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Ethnicity (NIH/OMB)', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '111', 'groupId': 'BG000'}]}], 'categories': [{'title': 'Hispanic or Latino', 'measurements': [{'value': '1', 'groupId': 'BG000'}]}, {'title': 'Not Hispanic or Latino', 'measurements': [{'value': '110', 'groupId': 'BG000'}]}, {'title': 'Unknown or Not Reported', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Race/Ethnicity, Customized', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '111', 'groupId': 'BG000'}]}], 'categories': [{'title': 'American Indian or Alaska Native', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Asian', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Black or African American', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Multiple', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Native Hawaiian or Other Pacific Islander', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'White', 'measurements': [{'value': '111', 'groupId': 'BG000'}]}, {'title': 'Other', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Eastern Cooperative Oncology Group (ECOG) Performance Status', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '111', 'groupId': 'BG000'}]}], 'categories': [{'title': '0 (Fully active, no restrictions)', 'measurements': [{'value': '87', 'groupId': 'BG000'}]}, {'title': '1 (Restricted but ambulatory)', 'measurements': [{'value': '24', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'description': "A scale to assess a patient's disease status. 0 = Fully active, able to carry out all pre-disease performance without restriction; 1 = Restricted in physically strenuous activity, ambulatory and able to carry out work of a light nature; 2 = Ambulatory and capable of all self-care, unable to carry out any work activities. Up and about \\> 50% of waking hours; 3 = Capable of only limited self-care, confined to bed or chair \\> 50% of waking hours; 4 = Completely disabled, confined to bed or chair; 5 = Dead.", 'unitOfMeasure': 'Participants'}, {'title': 'Log2(Intratumoral Cluster of Differentiation 8-positive (CD8+) Cell Density)', 'classes': [{'title': 'Primary completion', 'denoms': [{'units': 'Participants', 'counts': [{'value': '91', 'groupId': 'BG000'}]}], 'categories': [{'measurements': [{'value': '8.041', 'spread': '1.903', 'groupId': 'BG000'}]}]}, {'title': 'Final analysis', 'denoms': [{'units': 'Participants', 'counts': [{'value': '93', 'groupId': 'BG000'}]}], 'categories': [{'measurements': [{'value': '8.109', 'spread': '1.940', 'groupId': 'BG000'}]}]}], 'paramType': 'MEAN', 'description': 'CD8+ cell density was assessed from tumor biopsy samples using CD8-specific immunohistochemistry.', 'unitOfMeasure': 'Log2 CD8+ cells/mm²', 'dispersionType': 'STANDARD_DEVIATION', 'populationDescription': 'Participants with non-missing data. Baseline data is available for 91 participants who had data available for analysis at the time of primary completion (26 June 2017). Baseline data is also presented for 93 participants who had data available at final analysis (25 December 2020).'}], 'populationDescription': 'Participants who received at least 1 dose of talimogene laherparepvec.'}}, 'documentSection': {'largeDocumentModule': {'largeDocs': [{'date': '2015-09-21', 'size': 3249820, 'label': 'Study Protocol', 'hasIcf': False, 'hasSap': False, 'filename': 'Prot_000.pdf', 'typeAbbrev': 'Prot', 'uploadDate': '2018-06-21T08:02', 'hasProtocol': True}, {'date': '2014-08-20', 'size': 504332, 'label': 'Statistical Analysis Plan', 'hasIcf': False, 'hasSap': True, 'filename': 'SAP_001.pdf', 'typeAbbrev': 'SAP', 'uploadDate': '2018-06-21T08:02', 'hasProtocol': False}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NA', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'SINGLE_GROUP'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 112}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2015-04-07', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2021-11', 'completionDateStruct': {'date': '2020-12-25', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2021-11-26', 'studyFirstSubmitDate': '2014-11-11', 'resultsFirstSubmitDate': '2018-06-21', 'studyFirstSubmitQcDate': '2015-02-12', 'lastUpdatePostDateStruct': {'date': '2021-11-30', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2018-06-21', 'studyFirstPostDateStruct': {'date': '2015-02-19', 'type': 'ESTIMATED'}, 'resultsFirstPostDateStruct': {'date': '2018-07-18', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2017-06-26', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Odds Ratio of Baseline Intratumoral CD8+ Cell Density and Objective Response Rate', 'timeFrame': 'Intratumoral CD8+ cell density: Baseline. Response: every 12 weeks until disease progression beyond 6 months of treatment or the start of new anticancer therapy; median time on follow-up at primary completion = 59 weeks (min 3 to max 116 weeks)', 'description': 'A univariate logistic regression model was performed to evaluate baseline log2(CD8+ cell density) as a predictor of objective response.\n\nResponse was assessed according to the modified version of the World Health Organization (WHO) response criteria. Objective response rate (ORR) was defined as the percentage of participants with a complete response (CR) or partial response (PR) according to the modified WHO criteria.\n\nThe unadjusted odds ratio of log2(baseline intratumoral CD8+ cell density) for objective response rate is reported.'}], 'secondaryOutcomes': [{'measure': 'Odds Ratio of Baseline Intratumoral CD8+ Cell Density and Durable Response Rate', 'timeFrame': 'Intratumoral CD8+ cell density: Baseline. Response: every 12 weeks until disease progression beyond 6 months of treatment or the start of new anticancer therapy; median time on follow-up: PC: 59 weeks (3 to 116 weeks); FA: 108 weeks (2.7 to 245.6)', 'description': 'A univariate logistic regression model was performed to evaluate baseline log2(CD8+ cell density) as a predictor of durable response.\n\nResponse was assessed according to the modified version of the World Health Organization (WHO) response criteria. Durable response rate (DRR) was defined as the percentage of participants with an objective response lasting continuously for 6 months and starting any time within 12 months of initiating therapy.\n\nThe unadjusted odds ratio of log2(baseline intratumoral CD8+ cell density) for durable response rate is reported.\n\nPrimary completion is defined as PC and final analysis is defined as FA.'}, {'measure': 'Hazards Ratio of Baseline Intratumoral CD8+ Cell Density and Duration of Response', 'timeFrame': 'Intratumoral CD8+ cell density: Baseline. Response: every 12 weeks until disease progression beyond 6 months of treatment or the start of new anticancer therapy; median time on follow-up: PC: 59 weeks (3 to 116 weeks); FA: 108 weeks (2.7 to 245.6 weeks)', 'description': 'A Cox proportional hazards regression model was performed to evaluate baseline log2(CD8+ cell density) as a predictor of duration of response.\n\nResponse was assessed according to the modified version of the World Health Organization (WHO) response criteria. Duration of response (DOR) is defined as the longest individual period from entering an objective response (CR/PR) to the first documented evidence of the participant no longer meeting the criteria for being in the response (i.e. an overall response of either stable disease \\[SD\\] as compared with baseline or progressive disease \\[PD\\]).\n\nThe unadjusted hazard ratio of log2(baseline intratumoral CD8+ cell density) for duration of response is reported.'}, {'measure': 'Correlation Between Baseline Intratumoral CD8+ Cell Density and Changes in Tumor Burden', 'timeFrame': 'Intratumoral CD8+ cell density: Baseline; Tumor burden: First dose of study drug until primary completion date (26 June 2017) or end of follow-up; median time on follow-up: PC: 59 weeks (3 to 116 weeks); FA: 108 weeks (2.7 to 245.6 weeks)', 'description': "Pearson's correlation coefficient (r) was estimated to assess the relationship between baseline log2(CD8+ cell density) and the maximum decrease in measurable tumor burden.\n\nTumor burden is the sum of the products of the 2 largest perpendicular diameters (SPD) for all index lesions selected at baseline.\n\nThe Pearson's correlation coefficient (r) of log2(baseline intratumoral CD8+ cell density) and the maximum decrease in tumor burden is reported.\n\nPrimary completion is defined as PC and final analysis is defined as FA."}, {'measure': 'Odds Ratio of Change From Baseline Intratumoral CD8+ Cell Density and Objective Response Rate', 'timeFrame': 'CD8+ cell density: Baseline & Week 6. Response: every 12 weeks until disease progression beyond 6 months of treatment or the start of new anticancer therapy; median time on follow-up: PC: 59 weeks (3 to 116 weeks); FA: 108 weeks (2.7 to 245.6 weeks)', 'description': 'A univariate logistic regression model was performed to evaluate change from baseline to week 6 in log2(CD8+ cell density) in uninjected tumors as a predictor of objective response.\n\nResponse was assessed according to the modified version of the World Health Organization (WHO) response criteria. Objective response rate (ORR) was defined as the percentage of participants with a complete response or partial response according to the modified WHO criteria.\n\nThe unadjusted odds ratio of log2(change from baseline intratumoral CD8+ cell density) for objective response rate is reported.\n\nIntratumoral CD8+ Cell density has been shortened to "CD8+ cell density" in the time frame due to character limit. Primary completion is defined as PC and final analysis is defined as FA.'}, {'measure': 'Odds Ratio of Change From Baseline in Intratumoral CD8+ Cell Density and Durable Response Rate', 'timeFrame': 'CD8+ cell density: Baseline & Week 6. Response: every 12 weeks until disease progression beyond 6 months of treatment or the start of new anticancer therapy; median time on follow-up: PC: 59 weeks (3 to 116 weeks); FA: 108 weeks (2.7 to 245.6 weeks)', 'description': 'A univariate logistic regression model was performed to evaluate change from baseline to week 6 in log2(CD8+ cell density) in uninjected lesions as a predictor of durable response.\n\nResponse was assessed according to the modified version of the World Health Organization (WHO) response criteria. Durable response rate (DRR) was defined as the percentage of participants with an objective response lasting continuously for 6 months and starting any time within 12 months of initiating therapy.\n\nThe unadjusted odds ratio of log2(change from baseline in intratumoral CD8+ cell density) for durable response rate is reported.\n\nIntratumoral CD8+ Cell density has been shortened to "CD8+ cell density" in the time frame due to character limit. Primary completion is defined as PC and final analysis is defined as FA.'}, {'measure': 'Hazard Ratio of Change From Baseline in Intratumoral CD8+ Cell Density and Duration of Response', 'timeFrame': 'CD8+ cell density: Baseline & Week 6. Response: every 12 weeks until disease progression beyond 6 months of treatment or the start of new anticancer therapy; median time on follow-up: PC: 59 weeks (3 to 116 weeks); FA: 108 weeks (2.7 to 245.6 weeks)', 'description': 'A Cox proportional hazards regression model was performed to evaluate change from baseline in log2(CD8+ cell density) as a predictor of duration of response.\n\nResponse was assessed according to the modified version of the World Health Organization (WHO) response criteria. Duration of response (DOR) is defined as the longest individual period from entering an objective response (CR/PR) to the first documented evidence of the participant no longer meeting the criteria for being in the response (i.e. an overall response of either stable disease \\[SD\\] as compared with baseline or progressive disease \\[PD\\]).\n\nThe unadjusted hazard ratio of log2(change from baseline intratumoral CD8+ cell density) for duration of response is reported.\n\nIntratumoral CD8+ Cell density has been shortened to "CD8+ cell density" in the time frame due to character limit. Primary completion is defined as PC and final analysis is defined as FA.'}, {'measure': 'Correlation Between Change From Baseline in Intratumoral CD8+ Cell Density and Changes in Tumor Burden', 'timeFrame': 'CD8+ cell density: Baseline & Week 6. Response: every 12 weeks until disease progression beyond 6 months of treatment or the start of new anticancer therapy; median time on follow-up: PC: 59 weeks (3 to 116 weeks); FA: 108 weeks (2.7 to 245.6 weeks)', 'description': 'Pearson\'s correlation coefficient (r) was estimated to assess the relationship between change from baseline in log2(CD8+ cell density) in uninjected lesions and the maximum decrease in measurable tumor burden.\n\nTumor burden is the sum of the products of the 2 largest perpendicular diameters (SPD) for all index lesions selected at baseline.\n\nThe Pearson\'s correlation coefficient (r) of log2(change from baseline intratumoral CD8+ cell density) and the maximum decrease in tumor burden is reported.\n\nIntratumoral CD8+ Cell density has been shortened to "CD8+ cell density" in the time frame due to character limit. Primary completion is defined as PC and final analysis is defined as FA.'}, {'measure': 'Objective Response Rate', 'timeFrame': 'Response was assessed every 12 weeks until PD beyond 6 months of treatment or the start of new anticancer therapy; median time on follow-up at time of primary completion: 59 weeks (3 to 116 weeks); final analysis: 108 weeks (2.7 to 245.6 weeks)', 'description': 'Objective Response rate is defined as the percentage of participants with either a CR or PR based on Modified WHO Response Criteria.\n\nCR: Complete disappearance of all index lesions, all non-index lesions, and any new tumors which might have appeared. Any residual cutaneous or subcutaneous index lesions must be documented by representative biopsy to not contain viable tumor.\n\nPR: Disappearance of all index lesions with persistence of one or more non-index tumor(s), or, 50% or greater reduction in the 2 largest perpendicular diameters (SPD) of all index lesions as compared to baseline, and disappearance or persistence of non-index lesions.'}, {'measure': 'Duration of Response', 'timeFrame': 'Response was assessed every 12 weeks until PD beyond 6 months of treatment or the start of new anticancer therapy; median time on follow-up at time of primary completion: 59 weeks (3 to 116 weeks); final analysis: 108 weeks (2.7 to 245.6 weeks)', 'description': 'Duration of response (DOR) was defined as the longest individual period from entering an objective response (CR/PR) to the first documented evidence of the participant no longer meeting the criteria for objective response (i.e. an overall response of either stable disease \\[SD\\] as compared with baseline or progressive disease \\[PD\\]).\n\nSD: Neither sufficient tumor shrinkage of index lesion to qualify for response (PR or CR) nor sufficient tumor increase of index lesion to qualify for PD, with no increase in size of non-index lesions.\n\nPD: A \\> 25% increase in the sum of the SPD of all index tumors since baseline, or the unequivocal appearance of a new tumor since the last response assessment time point, or unequivocal progression of one or more non-index lesions.\n\nParticipants last reported to be either a CR or PR were censored at that time point.'}, {'measure': 'Time to Treatment Failure', 'timeFrame': 'From first dose of study drug until primary completion date of 26 June 2017, or end of follow-up; median time on follow-up at primary completion was 59 weeks (3 to 116 weeks); final analysis was 108 weeks (2.7 to 245.6 weeks)', 'description': 'Time to treatment failure (TTF) was calculated from first dosing until one or more of the following: (1) clinically relevant disease progression (PDr); (2) death from any cause; (3) non clinically relevant disease progression (PDn) associated with a requirement for alternative therapy as the reason for ending treatment or start of new anti-cancer therapy. Participants with no event were censored at their last evaluable tumor assessment.'}, {'measure': 'Durable Response Rate', 'timeFrame': 'Response was assessed every 12 weeks until PD beyond 6 months of treatment or the start of new anticancer therapy; median time on follow-up at time of primary completion: 59 weeks (3 to 116 weeks); final analysis: 108 weeks (2.7 to 245.6 weeks)', 'description': 'Durable response rate (DRR) was defined as the percentage of participants with an objective response (CR or PR) based on modified WHO response criteria lasting continuously for 6 months and starting any time within 12 months of initiating therapy.'}, {'measure': 'Overall Survival', 'timeFrame': 'From first dose of study drug until primary completion date of 26 June 2017, or end of follow-up; median time on follow-up at primary completion was 59 weeks (3 to 116 weeks); final analysis was 108 weeks (2.7 to 245.6 weeks)', 'description': 'Overall survival (OS) was defined as the time from the date of first dose to the date of death from any cause.\n\nOS time was censored at the last date the participant was known to be alive when the confirmation of death is absent or unknown.'}, {'measure': 'Change From Baseline in Tumor Burden', 'timeFrame': 'Baseline and Day 1 of cycle 6, 12 , 18, 24, 30, 36, 42, 48, 54, 60, 66, 72, 78, 84, 90, 96, 102, 108, 114, and 120. The first cycle was 21 days and all subsequent cycles were 14 days.', 'description': 'Tumor burden is the sum of the products of the 2 largest perpendicular diameters (SPD) for all index lesions selected at baseline.\n\nChange from baseline in tumor burden was assessed in participants with an objective response.'}, {'measure': 'Number of Participants With Adverse Events', 'timeFrame': 'From first dose through 30 days after last dose of talimogene laherparepvec; median duration of treatment was 25.143 weeks (range 0.14 to 241.43 weeks)', 'description': 'The severity of each adverse event (AE) was assessed according to the Common Terminology Criteria for Adverse Events (CTCAE), version 3.0 grading scale, where Grade 1 = Mild AE Grade 2 = Moderate AE Grade 3 = Severe AE Grade 4 = Life-threatening or disabling AE Grade 5 = Death related to AE Treatment-related adverse events (TRAE) were those assessed by the investigator as possibly related to talimogene laherparepvec.'}]}, 'oversightModule': {'oversightHasDmc': False}, 'conditionsModule': {'keywords': ['T-VEC', 'CD8+ cell density', 'objective response rate', 'unresected', 'Melanoma'], 'conditions': ['Unresected Stage IIIb to IVM1c Melanoma']}, 'referencesModule': {'references': [{'pmid': '33785610', 'type': 'BACKGROUND', 'citation': 'Malvehy J, Samoylenko I, Schadendorf D, Gutzmer R, Grob JJ, Sacco JJ, Gorski KS, Anderson A, Pickett CA, Liu K, Gogas H. Talimogene laherparepvec upregulates immune-cell populations in non-injected lesions: findings from a phase II, multicenter, open-label study in patients with stage IIIB-IVM1c melanoma. J Immunother Cancer. 2021 Mar;9(3):e001621. doi: 10.1136/jitc-2020-001621.'}], 'seeAlsoLinks': [{'url': 'http://www.amgentrials.com', 'label': 'AmgenTrials clinical trials website'}]}, 'descriptionModule': {'briefSummary': 'The study is a phase 2, multi centered, single arm study designed to evaluate the correlation between cluster of differentiation 8-positive (CD8+) cell density and objective response rate in adults with unresected stage IIIB to IVM1c melanoma. This study will also evaluate the safety and tolerability profile of talimogene laherparepvec.', 'detailedDescription': 'The study will explore the hypothesis that intratumoral CD8+ cell density at baseline correlates with objective response rate in adults with unresected stage IIIB to IVMIc melanoma treated with talimogene laherparepvec.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n1. Provided informed consent prior to initiation of any study-specific activities/procedures\n2. Subject with stage IIIB to IVM1c melanoma for whom surgery is not recommended\n3. Candidate for intralesional therapy\n4. Measurable disease with greatest diameter ≥ 10 mm\n5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1\n6. Adequate organ function\n\nOther Inclusion Criteria May Apply\n\nExclusion Criteria:\n\n1. Clinically active cerebral metastases.\n2. Bone metastases\n3. Primary ocular or mucosal melanoma\n4. Active herpetic skin lesions or prior complications of herpes simplex virus type 1 (HSV-1) infection (eg, herpetic keratitis or encephalitis)\n5. Requires intermittent or chronic systemic (intravenous or oral) treatment with an antiherpetic drug (eg, acyclovir), other than intermittent topical use\n6. Female subject is pregnant or breast-feeding, or planning to become pregnant during study treatment and through 3 months after the last dose of talimogene laherparepvec\n7. Female subject of childbearing potential who is unwilling to use acceptable method(s) of effective contraception\n\nOther Exclusion Criteria May Apply'}, 'identificationModule': {'nctId': 'NCT02366195', 'acronym': 'TVEC-325', 'briefTitle': 'Single-arm Trial to Evaluate the Role of the Immune Response to Talimogene Laherparepvec in Unresected Melanoma', 'organization': {'class': 'INDUSTRY', 'fullName': 'Amgen'}, 'officialTitle': 'A Phase 2, Multicenter, Open-label, Single-arm Trial to Evaluate the Correlation Between Objective Response Rate and Baseline Intratumoral CD8+ Cell Density in Subjects With Unresected Stage IIIB to IVM1c Melanoma Treated With Talimogene Laherparepvec', 'orgStudyIdInfo': {'id': '20120325'}, 'secondaryIdInfos': [{'id': '2013-005552-15', 'type': 'EUDRACT_NUMBER'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Talimogene Laherparepvec', 'description': 'Talimogene laherparepvec was administered by intralesional injection into injectable cutaneous, subcutaneous, and nodal lesions at an initial dose of 10⁶ plaque-forming units (PFU) per mL on day 1 followed by a dose of 10⁸ PFU/mL 21 days after the initial dose and every 14 days thereafter. Participants were treated with talimogene laherparepvec until they achieved a complete response, all injectable tumors had disappeared, clinically significant (resulting in clinical deterioration or requiring change of therapy) disease progression beyond 6 months of treatment, per modified World Health Organization (WHO) response criteria, or intolerance of study treatment, whichever occurred first.', 'interventionNames': ['Drug: Talimogene Laherparepvec']}], 'interventions': [{'name': 'Talimogene Laherparepvec', 'type': 'DRUG', 'otherNames': ['IMLYGIC®'], 'description': 'The initial dose of talimogene laherparepvec is up to 4.0 mL of 10\\^6 PFU/mL. Subsequent doses of talimogene laherparepvec are up to 4.0 mL of 10\\^8 PFU/mL.', 'armGroupLabels': ['Talimogene Laherparepvec']}]}, 'contactsLocationsModule': {'locations': [{'zip': '84112', 'city': 'Salt Lake City', 'state': 'Utah', 'country': 'United States', 'facility': 'Research Site', 'geoPoint': {'lat': 40.76078, 'lon': -111.89105}}, {'zip': '5020', 'city': 'Salzburg', 'country': 'Austria', 'facility': 'Research Site', 'geoPoint': {'lat': 47.79941, 'lon': 13.04399}}, {'zip': '1090', 'city': 'Vienna', 'country': 'Austria', 'facility': 'Research Site', 'geoPoint': {'lat': 48.20849, 'lon': 16.37208}}, {'zip': '1000', 'city': 'Brussels', 'country': 'Belgium', 'facility': 'Research Site', 'geoPoint': {'lat': 50.85045, 'lon': 4.34878}}, {'zip': '1200', 'city': 'Brussels', 'country': 'Belgium', 'facility': 'Research Site', 'geoPoint': {'lat': 50.85045, 'lon': 4.34878}}, {'zip': '4000', 'city': 'Liège', 'country': 'Belgium', 'facility': 'Research Site', 'geoPoint': {'lat': 50.63373, 'lon': 5.56749}}, {'zip': '92100', 'city': 'Boulogne-Billancourt', 'country': 'France', 'facility': 'Research Site', 'geoPoint': {'lat': 48.83545, 'lon': 2.24128}}, {'zip': '13385', 'city': 'Marseille', 'country': 'France', 'facility': 'Research Site', 'geoPoint': {'lat': 43.29695, 'lon': 5.38107}}, {'zip': '44093', 'city': 'Nantes', 'country': 'France', 'facility': 'Research Site', 'geoPoint': {'lat': 47.21725, 'lon': -1.55336}}, {'zip': '75010', 'city': 'Paris', 'country': 'France', 'facility': 'Research Site', 'geoPoint': {'lat': 48.85341, 'lon': 2.3488}}, {'zip': '86021', 'city': 'Poitiers', 'country': 'France', 'facility': 'Research Site', 'geoPoint': {'lat': 46.58261, 'lon': 0.34348}}, {'zip': '45147', 'city': 'Essen', 'country': 'Germany', 'facility': 'Research Site', 'geoPoint': {'lat': 51.45657, 'lon': 7.01228}}, {'zip': '60590', 'city': 'Frankfurt am Main', 'country': 'Germany', 'facility': 'Research Site', 'geoPoint': {'lat': 50.11552, 'lon': 8.68417}}, {'zip': '30625', 'city': 'Hanover', 'country': 'Germany', 'facility': 'Research Site', 'geoPoint': {'lat': 52.37052, 'lon': 9.73322}}, {'zip': '69120', 'city': 'Heidelberg', 'country': 'Germany', 'facility': 'Research Site', 'geoPoint': {'lat': 49.40768, 'lon': 8.69079}}, {'zip': '11527', 'city': 'Athens', 'country': 'Greece', 'facility': 'Research Site', 'geoPoint': {'lat': 37.98376, 'lon': 23.72784}}, {'zip': '18547', 'city': 'Athens', 'country': 'Greece', 'facility': 'Research Site', 'geoPoint': {'lat': 37.98376, 'lon': 23.72784}}, {'zip': '71110', 'city': 'Heraklion - 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There is no end date for eligibility to submit a data sharing request for this study.', 'ipdSharing': 'YES', 'description': 'De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request', 'accessCriteria': 'Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors, and if not approved, may be further arbitrated by a Data Sharing Independent Review Panel. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the link below.'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Amgen', 'class': 'INDUSTRY'}, 'responsibleParty': {'type': 'SPONSOR'}}}}