Ignite Creation Date:
2025-12-25 @ 5:03 AM
Ignite Modification Date:
2026-03-08 @ 1:06 AM
Study NCT ID:
NCT02335918
Status:
COMPLETED
Last Update Posted:
2019-12-09
First Post:
2014-12-18
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
A Dose Escalation and Cohort Expansion Study of Anti-CD27 (Varlilumab) and Anti-PD-1 (Nivolumab) in Advanced Refractory Solid Tumors
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24', 'submissionTracking': {'submissionInfos': [{'resetDate': '2022-01-14', 'releaseDate': '2021-12-17'}], 'estimatedResultsFirstSubmitDate': '2021-12-17'}}, 'conditionBrowseModule': {'meshes': [{'id': 'D000077195', 'term': 'Squamous Cell Carcinoma of Head and Neck'}, {'id': 'D015179', 'term': 'Colorectal Neoplasms'}, {'id': 'D002292', 'term': 'Carcinoma, Renal Cell'}, {'id': 'D005909', 'term': 'Glioblastoma'}], 'ancestors': [{'id': 'D002294', 'term': 'Carcinoma, Squamous Cell'}, {'id': 'D002277', 'term': 'Carcinoma'}, {'id': 'D009375', 'term': 'Neoplasms, Glandular and Epithelial'}, {'id': 'D009370', 'term': 'Neoplasms by Histologic Type'}, {'id': 'D009369', 'term': 'Neoplasms'}, {'id': 'D006258', 'term': 'Head and Neck Neoplasms'}, {'id': 'D009371', 'term': 'Neoplasms by Site'}, {'id': 'D007414', 'term': 'Intestinal Neoplasms'}, {'id': 'D005770', 'term': 'Gastrointestinal Neoplasms'}, {'id': 'D004067', 'term': 'Digestive System Neoplasms'}, {'id': 'D004066', 'term': 'Digestive System Diseases'}, {'id': 'D005767', 'term': 'Gastrointestinal Diseases'}, {'id': 'D003108', 'term': 'Colonic Diseases'}, {'id': 'D007410', 'term': 'Intestinal Diseases'}, {'id': 'D012002', 'term': 'Rectal Diseases'}, {'id': 'D000230', 'term': 'Adenocarcinoma'}, {'id': 'D007680', 'term': 'Kidney Neoplasms'}, {'id': 'D014571', 'term': 'Urologic Neoplasms'}, {'id': 'D014565', 'term': 'Urogenital Neoplasms'}, {'id': 'D052776', 'term': 'Female Urogenital Diseases'}, {'id': 'D005261', 'term': 'Female Urogenital Diseases and Pregnancy Complications'}, {'id': 'D000091642', 'term': 'Urogenital Diseases'}, {'id': 'D007674', 'term': 'Kidney Diseases'}, {'id': 'D014570', 'term': 'Urologic Diseases'}, {'id': 'D052801', 'term': 'Male Urogenital Diseases'}, {'id': 'D001254', 'term': 'Astrocytoma'}, {'id': 'D005910', 'term': 'Glioma'}, {'id': 'D018302', 'term': 'Neoplasms, Neuroepithelial'}, {'id': 'D017599', 'term': 'Neuroectodermal Tumors'}, {'id': 'D009373', 'term': 'Neoplasms, Germ Cell and Embryonal'}, {'id': 'D009380', 'term': 'Neoplasms, Nerve Tissue'}]}, 'interventionBrowseModule': {'meshes': [{'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', 'PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NA', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'SINGLE_GROUP'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 175}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2015-01'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2018-11', 'dispFirstSubmitDate': '2019-12-03', 'completionDateStruct': {'date': '2018-12-12', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2019-12-05', 'studyFirstSubmitDate': '2014-12-18', 'dispFirstSubmitQcDate': '2019-12-03', 'studyFirstSubmitQcDate': '2015-01-07', 'dispFirstPostDateStruct': {'date': '2019-12-05', 'type': 'ACTUAL'}, 'lastUpdatePostDateStruct': {'date': '2019-12-09', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2015-01-12', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2018-12-12', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Phase I: Number of participants with treatment-related adverse events as determined by CTCAE v4.0, dose-limiting toxicities, and laboratory abnormalities.', 'timeFrame': 'Safety follow-up is 100 days from last study drug dose.'}, {'measure': 'Phase II: Preliminary antitumor activity of the combination of varlilumab and nivolumab as measured by objective response rate (ORR) in patients with CRC, ovarian cancer, RCC and SCCHN and Overall Survival-12 months in GBM.', 'timeFrame': 'Evaluated every 8 weeks following treatment initiation until treatment is discontinued or disease progression, for up to 3 years.'}]}, 'oversightModule': {'oversightHasDmc': False}, 'conditionsModule': {'keywords': ['Opdivo®'], 'conditions': ['Squamous Cell Carcinoma of the Head and Neck (SCCHN)', 'Ovarian Carcinoma-Enrollment Completed', 'Colorectal Cancer (CRC)-Enrollment Completed', 'Renal Cell Carcinoma (RCC) (Phase ll Only)', 'Glioblastoma (GBM) (Phase ll Only)-Enrollment Completed']}, 'referencesModule': {'references': [{'pmid': '35940825', 'type': 'DERIVED', 'citation': 'Sanborn RE, Pishvaian MJ, Callahan MK, Weise A, Sikic BI, Rahma O, Cho DC, Rizvi NA, Sznol M, Lutzky J, Bauman JE, Bitting RL, Starodub A, Jimeno A, Reardon DA, Kaley T, Iwamoto F, Baehring JM, Subramaniam DS, Aragon-Ching JB, Hawthorne TR, Rawls T, Yellin M, Keler T. Safety, tolerability and efficacy of agonist anti-CD27 antibody (varlilumab) administered in combination with anti-PD-1 (nivolumab) in advanced solid tumors. J Immunother Cancer. 2022 Aug;10(8):e005147. doi: 10.1136/jitc-2022-005147.'}]}, 'descriptionModule': {'briefSummary': 'This is a study to determine the clinical benefit (how well the drug works), safety, and tolerability of combining varlilumab and nivolumab (also known as Opdivo® , BMS-936558). Both drugs target the immune system and may act to promote anti-cancer effects.', 'detailedDescription': 'Varlilumab is a fully human monoclonal antibody that binds to a molecule called CD27 found on certain immune cells and may act to promote anti-tumor effects.\n\nNivolumab is a fully human monoclonal antibody that binds to a molecule called PD-1 on immune cells and promotes anti-tumor effects.\n\nEligible patients that enroll in the dose escalation portion of the study will be assigned to one of three dose levels of varlilumab in combination with 3 mg/kg of nivolumab. The first phase of the study will test the safety profile of the combination and determine which dose will be studied in Phase ll of the overall study.\n\nDuring Phase ll, depending on cancer type, groups of patients will be enrolled and receive varlilumab at a dose of either 3 mg/kg every 2 weeks, 3 mg/kg every 12 weeks, or 0.3 mg/kg every 4 weeks in combination with nivolumab at 240 mg.\n\nAll patients enrolled in the study will be closely monitored to determine if there is response to the treatment as well as for any side effects that may occur.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Key Inclusion Criteria:\n\n1. Histologically-diagnosed advanced (unresectable and/or metastatic) Non-small Cell Lung Cancer (Phase l only), Melanoma (Phase l only), Colorectal, Head and Neck SCC (squamous cell carcinoma), Ovarian Cancer, Glioblastoma or Renal Cell Carcinoma.\n\n * 1a. Head and Neck\n\n Stage III/IV squamous cell carcinoma; Tumor progression or recurrence within 6 months of last dose of platinum therapy in the adjuvant, primary, recurrent or metastatic setting (or within 9 months if the patient received \\> 1 platinum-based chemotherapy regimen in the metastatic setting). Active brain metastases or leptomeningeal metastases are excluded; nasopharyngeal cancer, confirmed recurrent or metastatic carcinoma of the nasopharynx and salivary gland or non-squamous histologies are also excluded.\n * 1b. Ovarian\n\n Recurrent or persistent epithelial ovarian, fallopian tube or primary peritoneal carcinoma requiring original or subsequent relapse histologic documentation. A platinum-taxane based chemotherapy regimen as frontline therapy must have been completed.\n\n Any histologic diagnosis of borderline, low malignant potential epithelial carcinoma are excluded.\n * 1c. Colorectal Cancer -Enrollment Completed\n\n Metastatic or recurrent; prior treatment progression during, after, or intolerant following the last administration of approved standard therapies (required therapies apply).\n * 1d. Glioblastoma -Enrollment Completed\n\n Have histologically confirmed World Health Organization Grade IV malignant glioma (glioblastoma).\n * Previous first line therapy with at least radiotherapy and temozolomide.\n * Participants must have shown unequivocal evidence of tumor progression.\n * More than one relapse, secondary glioblastoma and prior treatment with bevacizumab are excluded.\n\n An interval of at least 12 weeks from the completion of radiation therapy to start of study treatment is required.\n * 1e. Renal Cell Carcinoma\n\n Have histologically confirmed diagnosis of predominant clear cell renal cell carcinoma.\n * Must have received 1 or 2 prior anti-angiogenic therapies.\n * No more than 5 total previous regimens of systemic therapy, including cytokines and cytotoxic chemotherapy.\n * Disease progression during or after the last treatment regimen and within 6 months before study entry.\n2. No more than 5 prior anticancer regimens for advanced (recurrent, locally advanced or metastatic) disease except for patients with GBM which must have first recurrence of GBM by diagnostic biopsy or contrast enhanced magnetic resonance imaging (MRI).\n3. Measurable (target) disease.\n4. Life expectancy ≥ 12 weeks.\n5. If of childbearing potential (male or female), agree to practice an effective form of contraception during study treatment and for at least 23 weeks after for female and 31 weeks after for male following last treatment dose.\n\nKey Exclusion Criteria:\n\n1. History of severe hypersensitivity reactions to other monoclonal antibodies.\n2. Prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 antibody.\n3. Receipt of anti-CTLA-4 or anti-CD27 antibody within 3 months prior to the planned start of study treatment.\n4. Use of any monoclonal based therapies within 2-4 weeks prior to the first dose of study treatment.\n5. Chemotherapy within 21 days or at least 5 half-lives (whichever is shorter) prior to the planned start of study treatment.\n6. BRAF/MEK inhibitors within 2 weeks prior to the first dose of study treatment.\n7. Systemic radiation therapy within 4 weeks, prior focal radiotherapy within 2 weeks, or radiopharmaceuticals (strontium, samarium) within 8 weeks prior to the first dose of study treatment.\n8. Use of immunosuppressive medications within 4 weeks or systemic corticosteroids within 2 weeks prior to first dose of study treatment.\n9. Other prior malignancy, except for adequately treated basal or squamous cell skin cancer or in situ cancers; or any other cancer from which the patient has been disease-free for at least 3 years.\n10. Active, untreated central nervous system metastases.\n11. Active autoimmune disease or a documented history of autoimmune disease\n12. Active diverticulitis.\n13. Interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity.\n14. Significant cardiovascular disease'}, 'identificationModule': {'nctId': 'NCT02335918', 'briefTitle': 'A Dose Escalation and Cohort Expansion Study of Anti-CD27 (Varlilumab) and Anti-PD-1 (Nivolumab) in Advanced Refractory Solid Tumors', 'organization': {'class': 'INDUSTRY', 'fullName': 'Celldex Therapeutics'}, 'officialTitle': 'A Phase l/ll Dose Escalation and Cohort Expansion Study of the Safety, Tolerability and Efficacy of Anti-CD27 Antibody (Varlilumab) Administered in Combination With Anti-PD-1 (Nivolumab) in Advanced Refractory Solid Tumors', 'orgStudyIdInfo': {'id': 'CDX1127-02'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Varlilumab and Nivolumab', 'interventionNames': ['Drug: Combination of varlilumab and nivolumab']}], 'interventions': [{'name': 'Combination of varlilumab and nivolumab', 'type': 'DRUG', 'description': 'Phase I: Varlilumab dosing will be dependent on the cohort assigned in combination with 3 mg/kg of nivolumab every two weeks.\n\nPhase II: Patients with CRC, RCC or GBM enrolled in Phase ll will receive 3.0 mg/kg of varlilumab in combination with 240 mg of nivolumab every 2 weeks. Patients with SCCHN or ovarian cancer will receive varlilumab at a dose of either 3 mg/kg every 2 weeks, 3 mg/kg every 12 weeks, or 0.3 mg/kg every 4 weeks, in combination with 240 mg of nivolumab every 2 weeks.\n\nPatients may be discontinued from receiving study treatment based on the results of disease assessments or if experiencing intolerable side effects.', 'armGroupLabels': ['Varlilumab and Nivolumab']}]}, 'contactsLocationsModule': {'locations': [{'zip': '85719', 'city': 'Tucson', 'state': 'Arizona', 'country': 'United States', 'facility': 'University of Arizona Cancer Center', 'geoPoint': {'lat': 32.22174, 'lon': -110.92648}}, {'zip': '94304', 'city': 'Palo Alto', 'state': 'California', 'country': 'United States', 'facility': 'The Stanford Center for Clinical and Translational Education and Research', 'geoPoint': {'lat': 37.44188, 'lon': -122.14302}}, {'zip': '94115', 'city': 'San Francisco', 'state': 'California', 'country': 'United States', 'facility': 'UCSF Helen Diller Family Comprehensive Cancer Center', 'geoPoint': {'lat': 37.77493, 'lon': -122.41942}}, {'zip': '80045', 'city': 'Aurora', 'state': 'Colorado', 'country': 'United States', 'facility': 'University of Colorado Medical Center', 'geoPoint': {'lat': 39.72943, 'lon': -104.83192}}, {'zip': '06519', 'city': 'New Haven', 'state': 'Connecticut', 'country': 'United States', 'facility': 'Smilow Cancer Hospital at Yale University Cancer Center', 'geoPoint': {'lat': 41.30815, 'lon': -72.92816}}, {'zip': '20007', 'city': 'Washington D.C.', 'state': 'District of Columbia', 'country': 'United States', 'facility': 'Georgetown University', 'geoPoint': {'lat': 38.89511, 'lon': -77.03637}}, {'zip': '20037', 'city': 'Washington D.C.', 'state': 'District of Columbia', 'country': 'United States', 'facility': 'George Washington University School of Medicine and Health Sciences', 'geoPoint': {'lat': 38.89511, 'lon': -77.03637}}, {'zip': '33140', 'city': 'Miami Beach', 'state': 'Florida', 'country': 'United States', 'facility': 'Mount Sinai Medical Center', 'geoPoint': {'lat': 25.79065, 'lon': -80.13005}}, {'zip': '30060', 'city': 'Marietta', 'state': 'Georgia', 'country': 'United States', 'facility': 'Northwest Georgia Oncology Centers PC', 'geoPoint': {'lat': 33.9526, 'lon': -84.54993}}, {'zip': '46845', 'city': 'Fort Wayne', 'state': 'Indiana', 'country': 'United States', 'facility': 'Parkview Research Center', 'geoPoint': {'lat': 41.1306, 'lon': -85.12886}}, {'zip': '02115', 'city': 'Boston', 'state': 'Massachusetts', 'country': 'United States', 'facility': 'Dana Farber Cancer Institute', 'geoPoint': {'lat': 42.35843, 'lon': -71.05977}}, {'zip': '48201', 'city': 'Detroit', 'state': 'Michigan', 'country': 'United States', 'facility': 'Barbara Ann Karmanos Cancer Institute', 'geoPoint': {'lat': 42.33143, 'lon': -83.04575}}, {'zip': '10016', 'city': 'New York', 'state': 'New York', 'country': 'United States', 'facility': 'Laura and Isaac Perlmutter Cancer Center', 'geoPoint': {'lat': 40.71427, 'lon': -74.00597}}, {'zip': '10032', 'city': 'New York', 'state': 'New York', 'country': 'United States', 'facility': 'Columbia University Medical Center', 'geoPoint': {'lat': 40.71427, 'lon': -74.00597}}, {'zip': '10065', 'city': 'New York', 'state': 'New York', 'country': 'United States', 'facility': 'Memorial Sloan Kettering Cancer Center', 'geoPoint': {'lat': 40.71427, 'lon': -74.00597}}, {'zip': '27157', 'city': 'Winston-Salem', 'state': 'North Carolina', 'country': 'United States', 'facility': 'Wake Forest Baptist Health', 'geoPoint': {'lat': 36.09986, 'lon': -80.24422}}, {'zip': '44195', 'city': 'Cleveland', 'state': 'Ohio', 'country': 'United States', 'facility': 'Cleveland Clinic', 'geoPoint': {'lat': 41.4995, 'lon': -81.69541}}, {'zip': '97213', 'city': 'Portland', 'state': 'Oregon', 'country': 'United States', 'facility': 'Providence Health & Services', 'geoPoint': {'lat': 45.52345, 'lon': -122.67621}}, {'zip': '22031', 'city': 'Fairfax', 'state': 'Virginia', 'country': 'United States', 'facility': 'Inova Schar Cancer Institute Research', 'geoPoint': {'lat': 38.84622, 'lon': -77.30637}}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Celldex Therapeutics', 'class': 'INDUSTRY'}, 'collaborators': [{'name': 'Bristol-Myers Squibb', 'class': 'INDUSTRY'}], 'responsibleParty': {'type': 'SPONSOR'}}}, 'annotationSection': {'annotationModule': {'unpostedAnnotation': {'unpostedEvents': [{'date': '2021-12-17', 'type': 'RELEASE'}, {'date': '2022-01-14', 'type': 'RESET'}], 'unpostedResponsibleParty': 'Celldex Therapeutics'}}}}