Ignite Creation Date:
2025-12-25 @ 3:30 AM
Ignite Modification Date:
2025-12-26 @ 2:12 AM
Study NCT ID:
NCT04835805
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2025-09-30
First Post:
2021-04-06
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
A Study to Evaluate the Safety and Activity of Belvarafenib as a Single Agent and in Combination With Either Cobimetinib or Cobimetinib Plus Nivolumab in Patients With NRAS-mutant Advanced Melanoma.
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24', 'removedCountries': ['Norway']}, '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': 'C574276', 'term': 'cobimetinib'}, {'id': 'D000077594', 'term': 'Nivolumab'}], 'ancestors': [{'id': 'D061067', 'term': 'Antibodies, Monoclonal, Humanized'}, {'id': 'D000911', 'term': 'Antibodies, Monoclonal'}, {'id': 'D000906', 'term': 'Antibodies'}, {'id': 'D007136', 'term': 'Immunoglobulins'}, {'id': 'D007162', 'term': 'Immunoproteins'}, {'id': 'D001798', 'term': 'Blood Proteins'}, {'id': 'D011506', 'term': 'Proteins'}, {'id': 'D000602', 'term': 'Amino Acids, Peptides, and Proteins'}, {'id': 'D012712', 'term': 'Serum Globulins'}, {'id': 'D005916', 'term': 'Globulins'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE1'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NON_RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 65}}, 'statusModule': {'overallStatus': 'ACTIVE_NOT_RECRUITING', 'startDateStruct': {'date': '2021-05-13', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2025-09', 'completionDateStruct': {'date': '2025-12-31', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2025-09-29', 'studyFirstSubmitDate': '2021-04-06', 'studyFirstSubmitQcDate': '2021-04-06', 'lastUpdatePostDateStruct': {'date': '2025-09-30', 'type': 'ESTIMATED'}, 'studyFirstPostDateStruct': {'date': '2021-04-08', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2025-12-31', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Percentage of Participants With Dose Limiting Toxicity (DLTs)', 'timeFrame': '28 Days from Cycle 1, Day 1'}, {'measure': 'Percentage of Participants With Adverse Events', 'timeFrame': 'From Cycle 1, Day 1 Up to 4 Years', 'description': 'Severity determined according to National Cancer Institute Common Terminology Criteria for Adverse Events v5.0'}], 'secondaryOutcomes': [{'measure': 'Objective response rate (ORR) according to RECIST v1.1', 'timeFrame': 'Up to Approximately 4 Years', 'description': 'Defined as the percentage of participants with a CR or PR on two consecutive occasions \\>/= 4 weeks apart, as determined by the investigator according to RECIST v1.1'}, {'measure': 'Progression free survival (PFS) according to RECIST v1.1', 'timeFrame': 'Up to Approximately 4 Years', 'description': 'Defined as the time from the first study treatment to the first occurrence of disease progression or death from any cause (whichever occurs first), as determined by the investigator according to RECIST v1.1'}, {'measure': 'Duration of response (DOR) according to RECIST v1.1', 'timeFrame': 'Up to Approximately 4 Years', 'description': 'Defined as the time from the first occurrence of a confirmed objective response to disease progression or death from any cause (whichever occurs first), as determined by the investigator according to RECIST v1.1'}, {'measure': 'Overall survival (OS)', 'timeFrame': 'Up to Approximately 4 Years', 'description': 'Defined as the time from the first study treatment to death from any cause'}, {'measure': 'Plasma concentration of belvarafenib at specified timepoints', 'timeFrame': 'Up to 30 Days After the Final Dose of Study Drug'}, {'measure': 'Plasma concentration of cobimetinib at specified timepoints', 'timeFrame': 'Up to 30 Days After the Final Dose of Study Drug'}]}, 'oversightModule': {'isFdaRegulatedDrug': True, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'conditions': ['Melanoma']}, 'referencesModule': {'references': [{'pmid': '35587446', 'type': 'DERIVED', 'citation': 'Moschos SJ. War against NRAS-Mutant Melanoma Using Targeted Therapies Remains Challenging. Clin Cancer Res. 2022 Jul 15;28(14):2977-2979. doi: 10.1158/1078-0432.CCR-22-1256.'}]}, 'descriptionModule': {'briefSummary': 'This study will evaluate the safety, pharmacokinetics, and activity of belvarafenib as a single agent and in combination with either cobimetinib or cobimetinib plus nivolumab in patients with NRAS-mutant advanced melanoma who have received anti-PD-1/PD-L1 therapy.', 'detailedDescription': 'The study will evaluate three treatment regimens in three arms: a belvarafenib monotherapy arm (Belva arm); a belvarafenib plus cobimetinib arm (Belva + Cobi arm) in an initial dose-finding phase followed by an expansion phase and a belvarafenib plus cobimetinib plus nivolumab arm (Belva + Cobi + Nivo arm) in a run-in phase followed by an expansion phase.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* ECOG Performance Status of 0 or 1\n* Histologically confirmed, metastatic (recurrent or de novo Stage IV) or unresectable locally advanced (Stage III) cutaneous melanoma, that has progressed on or after treatment with anti-PD-1 or anti-PD-L1 therapy. Patients may have received up to two lines of systemic cancer therapy. Treatment with anti-PD-1/PD-L1 in the adjuvant setting is acceptable. Patients must have progressed disease at study entry\n* Documentation of NRAS mutation-positive within 5 years prior to screening\n* Tumor specimen availability\n* Adequate hematologic and end-organ function\n* Measurable disease per RECIST v1.1\n\nExclusion Criteria:\n\n* Prior treatment with a pan-RAF inhibitor\n* Treatment with systemic immunotherapy agents (e.g., anti-CTLA4, anti-PD(L)1, cytokine therapy, investigational therapy, etc.) within 28 days prior to C1D1\n* Symptomatic, untreated, or actively progressing CNS metastases\n* History or signs/symptoms of clinically significant cardiovascular disease\n* Known clinically significant liver disease\n* History of autoimmune disease or immune deficiency\n* Prior treatment with a MEK inhibitor (cobimetinib arm)\n* History of or evidence of retinal pathology on ophthalmologic examination (cobimetinib arm)\n* History of immune-related AE attributed to prior anti-PD(L)1 therapy that resulted in permanent discontinuation of anti-PD(L)1 therapy (nivolumab arm)'}, 'identificationModule': {'nctId': 'NCT04835805', 'briefTitle': 'A Study to Evaluate the Safety and Activity of Belvarafenib as a Single Agent and in Combination With Either Cobimetinib or Cobimetinib Plus Nivolumab in Patients With NRAS-mutant Advanced Melanoma.', 'organization': {'class': 'INDUSTRY', 'fullName': 'Genentech, Inc.'}, 'officialTitle': 'A Phase Ib, Open-Label, Multicenter Study to Evaluate the Safety, Pharmacokinetics, and Activity of Belvarafenib as a Single Agent and in Combination With Either Cobimetinib or Cobimetinib Plus Nivolumab in Patients With NRAS-Mutant Advanced Melanoma Who Have Received Anti-PD-1/PD-L1 Therapy', 'orgStudyIdInfo': {'id': 'GO42273'}, 'secondaryIdInfos': [{'id': '2020-003674-41', 'type': 'EUDRACT_NUMBER'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Belvarafenib Monotherapy', 'description': 'Twice daily (BID), continuous dosing.', 'interventionNames': ['Drug: Belvarafenib']}, {'type': 'EXPERIMENTAL', 'label': 'Belvarafenib Plus Cobimetinib', 'description': 'Recommended dose (RD) and schedule of belvarafenib and cobimetinib selected based on the safety data, tolerability, pharmacokinetics, and anti-tumor activity tested in dose-finding phase followed by an expansion phase.', 'interventionNames': ['Drug: Cobimetinib']}, {'type': 'EXPERIMENTAL', 'label': 'Belvarafenib Plus Cobimetinib Plus Nivolumab', 'description': 'Recommended dose (RD) and schedule of belvarafenib and cobimetinib plus nivolumab IV infusion every 4 weeks (Q4W) in a run-in phase followed by an expansion phase', 'interventionNames': ['Drug: Nivolumab']}], 'interventions': [{'name': 'Belvarafenib', 'type': 'DRUG', 'description': 'Twice daily (BID), continuous dosing', 'armGroupLabels': ['Belvarafenib Monotherapy']}, {'name': 'Cobimetinib', 'type': 'DRUG', 'description': 'Once daily (QD) or three times weekly (TIW) for 21 days, 7 days off', 'armGroupLabels': ['Belvarafenib Plus Cobimetinib']}, {'name': 'Nivolumab', 'type': 'DRUG', 'description': 'Once every 4 weeks (Q4W)', 'armGroupLabels': ['Belvarafenib Plus Cobimetinib Plus Nivolumab']}]}, 'contactsLocationsModule': {'locations': [{'zip': '94115', 'city': 'San Francisco', 'state': 'California', 'country': 'United States', 'facility': 'California Pacific Medical Center Research Institute', 'geoPoint': {'lat': 37.77493, 'lon': -122.41942}}, {'zip': '94158', 'city': 'San Francisco', 'state': 'California', 'country': 'United States', 'facility': 'UCSF Helen Diller Family CCC', 'geoPoint': {'lat': 37.77493, 'lon': -122.41942}}, {'zip': '80045', 'city': 'Aurora', 'state': 'Colorado', 'country': 'United States', 'facility': 'University of Colorado Cancer Center', 'geoPoint': {'lat': 39.72943, 'lon': -104.83192}}, {'zip': '21231', 'city': 'Baltimore', 'state': 'Maryland', 'country': 'United States', 'facility': 'Johns Hopkins Sidney Kimmel Comprehensive Cancer Center', 'geoPoint': {'lat': 39.29038, 'lon': -76.61219}}, {'zip': '63110', 'city': 'St Louis', 'state': 'Missouri', 'country': 'United States', 'facility': 'Washington University School of Medicine', 'geoPoint': {'lat': 38.62727, 'lon': -90.19789}}, {'zip': '10021', 'city': 'New York', 'state': 'New York', 'country': 'United States', 'facility': 'Memorial Sloan Kettering', 'geoPoint': {'lat': 40.71427, 'lon': -74.00597}}, {'zip': '2298', 'city': 'Waratah', 'state': 'New South Wales', 'country': 'Australia', 'facility': 'Calvary Mater Newcastle', 'geoPoint': {'lat': -32.90667, 'lon': 151.72647}}, {'zip': '3000', 'city': 'Melbourne', 'state': 'Victoria', 'country': 'Australia', 'facility': 'Peter MacCallum Cancer Centre-East Melbourne', 'geoPoint': {'lat': -37.814, 'lon': 144.96332}}, {'zip': '6009', 'city': 'Nedlands', 'state': 'Western Australia', 'country': 'Australia', 'facility': 'Linear Clinical Research Ltd', 'geoPoint': {'lat': -31.98184, 'lon': 115.8073}}, {'zip': 'K1H 8M2', 'city': 'Ottawa', 'state': 'Ontario', 'country': 'Canada', 'facility': 'Ottawa Hospital Regional Cancer Centre', 'geoPoint': {'lat': 45.41117, 'lon': -75.69812}}, {'zip': 'M5G 2M9', 'city': 'Toronto', 'state': 'Ontario', 'country': 'Canada', 'facility': 'Princess Margaret Hospital', 'geoPoint': {'lat': 43.70643, 'lon': -79.39864}}, {'zip': '12203', 'city': 'Berlin', 'country': 'Germany', 'facility': 'Charité - Universitätsmedizin Berlin', 'geoPoint': {'lat': 52.52437, 'lon': 13.41053}}, {'zip': '20246', 'city': 'Hamburg', 'country': 'Germany', 'facility': 'Universitätsklinikum Hamburg-Eppendorf', 'geoPoint': {'lat': 53.55073, 'lon': 9.99302}}, {'zip': '68167', 'city': 'Mannheim', 'country': 'Germany', 'facility': 'Klinikum Mannheim GmbH Universitätsklinikum', 'geoPoint': {'lat': 49.4891, 'lon': 8.46694}}, {'zip': '72076', 'city': 'Tübingen', 'country': 'Germany', 'facility': 'Universitatsklinikum Tubingen', 'geoPoint': {'lat': 48.52266, 'lon': 9.05222}}, {'zip': '05505', 'city': 'Seoul', 'country': 'South Korea', 'facility': 'Asan Medical Center - PPDS', 'geoPoint': {'lat': 37.566, 'lon': 126.9784}}], 'overallOfficials': [{'name': 'Clinical Trials', 'role': 'STUDY_DIRECTOR', 'affiliation': 'Hoffmann-La Roche'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'YES', 'description': "For eligible studies, qualified researchers may request access to individual patient level clinical data. See Roche's commitment to transparency of clinical study information here: https://go.roche.com/data\\_sharing"}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Genentech, Inc.', 'class': 'INDUSTRY'}, 'responsibleParty': {'type': 'SPONSOR'}}}}