A Dose Escalation and Cohort Expansion Study of Anti-CD27 (Varlilumab) and Anti-PD-1 (Nivolumab) in Advanced Refractory Solid Tumors
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
1 other identifier
interventional
175
1 country
19
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Jan 2015
Longer than P75 for phase_1
19 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
December 18, 2014
CompletedStudy Start
First participant enrolled
January 1, 2015
CompletedFirst Posted
Study publicly available on registry
January 12, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 12, 2018
CompletedStudy Completion
Last participant's last visit for all outcomes
December 12, 2018
CompletedDecember 9, 2019
November 1, 2018
3.9 years
December 18, 2014
December 5, 2019
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Phase I: Number of participants with treatment-related adverse events as determined by CTCAE v4.0, dose-limiting toxicities, and laboratory abnormalities.
Safety follow-up is 100 days from last study drug dose.
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.
Evaluated every 8 weeks following treatment initiation until treatment is discontinued or disease progression, for up to 3 years.
Study Arms (1)
Varlilumab and Nivolumab
EXPERIMENTALInterventions
Phase I: Varlilumab dosing will be dependent on the cohort assigned in combination with 3 mg/kg of nivolumab every two weeks. Phase 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. Patients may be discontinued from receiving study treatment based on the results of disease assessments or if experiencing intolerable side effects.
Eligibility Criteria
You may qualify if:
- 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.
- a. Head and Neck
- 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.
- b. Ovarian
- 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.
- Any histologic diagnosis of borderline, low malignant potential epithelial carcinoma are excluded.
- c. Colorectal Cancer -Enrollment Completed
- Metastatic or recurrent; prior treatment progression during, after, or intolerant following the last administration of approved standard therapies (required therapies apply).
- d. Glioblastoma -Enrollment Completed
- Have histologically confirmed World Health Organization Grade IV malignant glioma (glioblastoma).
- Previous first line therapy with at least radiotherapy and temozolomide.
- Participants must have shown unequivocal evidence of tumor progression.
- More than one relapse, secondary glioblastoma and prior treatment with bevacizumab are excluded.
- An interval of at least 12 weeks from the completion of radiation therapy to start of study treatment is required.
- e. Renal Cell Carcinoma
- +8 more criteria
You may not qualify if:
- History of severe hypersensitivity reactions to other monoclonal antibodies.
- Prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 antibody.
- Receipt of anti-CTLA-4 or anti-CD27 antibody within 3 months prior to the planned start of study treatment.
- Use of any monoclonal based therapies within 2-4 weeks prior to the first dose of study treatment.
- Chemotherapy within 21 days or at least 5 half-lives (whichever is shorter) prior to the planned start of study treatment.
- BRAF/MEK inhibitors within 2 weeks prior to the first dose of study treatment.
- 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.
- Use of immunosuppressive medications within 4 weeks or systemic corticosteroids within 2 weeks prior to first dose of study treatment.
- 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.
- Active, untreated central nervous system metastases.
- Active autoimmune disease or a documented history of autoimmune disease
- Active diverticulitis.
- Interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity.
- Significant cardiovascular disease
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Celldex Therapeuticslead
- Bristol-Myers Squibbcollaborator
Study Sites (19)
University of Arizona Cancer Center
Tucson, Arizona, 85719, United States
The Stanford Center for Clinical and Translational Education and Research
Palo Alto, California, 94304, United States
UCSF Helen Diller Family Comprehensive Cancer Center
San Francisco, California, 94115, United States
University of Colorado Medical Center
Aurora, Colorado, 80045, United States
Smilow Cancer Hospital at Yale University Cancer Center
New Haven, Connecticut, 06519, United States
Georgetown University
Washington D.C., District of Columbia, 20007, United States
George Washington University School of Medicine and Health Sciences
Washington D.C., District of Columbia, 20037, United States
Mount Sinai Medical Center
Miami Beach, Florida, 33140, United States
Northwest Georgia Oncology Centers PC
Marietta, Georgia, 30060, United States
Parkview Research Center
Fort Wayne, Indiana, 46845, United States
Dana Farber Cancer Institute
Boston, Massachusetts, 02115, United States
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, 48201, United States
Laura and Isaac Perlmutter Cancer Center
New York, New York, 10016, United States
Columbia University Medical Center
New York, New York, 10032, United States
Memorial Sloan Kettering Cancer Center
New York, New York, 10065, United States
Wake Forest Baptist Health
Winston-Salem, North Carolina, 27157, United States
Cleveland Clinic
Cleveland, Ohio, 44195, United States
Providence Health & Services
Portland, Oregon, 97213, United States
Inova Schar Cancer Institute Research
Fairfax, Virginia, 22031, United States
Related Publications (1)
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.
PMID: 35940825DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
December 18, 2014
First Posted
January 12, 2015
Study Start
January 1, 2015
Primary Completion
December 12, 2018
Study Completion
December 12, 2018
Last Updated
December 9, 2019
Record last verified: 2018-11