A Dose Escalation and Cohort Expansion Study of Anti-CD27 (Varlilumab) and Anti-PD-1 (Nivolumab) in Advanced Refractory Solid Tumors
NCT ID: NCT02335918
Last Updated: 2019-12-09
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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COMPLETED
PHASE1/PHASE2
175 participants
INTERVENTIONAL
2015-01-31
2018-12-12
Brief Summary
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Detailed Description
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Nivolumab is a fully human monoclonal antibody that binds to a molecule called PD-1 on immune cells and promotes anti-tumor effects.
Eligible 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.
During 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.
All 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.
Conditions
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Keywords
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Study Design
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NA
SINGLE_GROUP
TREATMENT
NONE
Study Groups
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Varlilumab and Nivolumab
Combination of varlilumab and nivolumab
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.
Interventions
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Combination of varlilumab and nivolumab
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
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Inclusion Criteria
* 1a. 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.
* 1b. 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.
* 1c. 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).
* 1d. 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.
* 1e. Renal Cell Carcinoma
Have histologically confirmed diagnosis of predominant clear cell renal cell carcinoma.
* Must have received 1 or 2 prior anti-angiogenic therapies.
* No more than 5 total previous regimens of systemic therapy, including cytokines and cytotoxic chemotherapy.
* Disease progression during or after the last treatment regimen and within 6 months before study entry.
2. 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).
3. Measurable (target) disease.
4. Life expectancy ≥ 12 weeks.
5. 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.
Exclusion Criteria
2. Prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 antibody.
3. Receipt of anti-CTLA-4 or anti-CD27 antibody within 3 months prior to the planned start of study treatment.
4. Use of any monoclonal based therapies within 2-4 weeks prior to the first dose of study treatment.
5. Chemotherapy within 21 days or at least 5 half-lives (whichever is shorter) prior to the planned start of study treatment.
6. BRAF/MEK inhibitors within 2 weeks prior to the first dose of study treatment.
7. 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.
8. Use of immunosuppressive medications within 4 weeks or systemic corticosteroids within 2 weeks prior to first dose of study treatment.
9. 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.
10. Active, untreated central nervous system metastases.
11. Active autoimmune disease or a documented history of autoimmune disease
12. Active diverticulitis.
13. Interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity.
14. Significant cardiovascular disease
18 Years
ALL
No
Sponsors
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Bristol-Myers Squibb
INDUSTRY
Celldex Therapeutics
INDUSTRY
Responsible Party
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Locations
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University of Arizona Cancer Center
Tucson, Arizona, United States
The Stanford Center for Clinical and Translational Education and Research
Palo Alto, California, United States
UCSF Helen Diller Family Comprehensive Cancer Center
San Francisco, California, United States
University of Colorado Medical Center
Aurora, Colorado, United States
Smilow Cancer Hospital at Yale University Cancer Center
New Haven, Connecticut, United States
Georgetown University
Washington D.C., District of Columbia, United States
George Washington University School of Medicine and Health Sciences
Washington D.C., District of Columbia, United States
Mount Sinai Medical Center
Miami Beach, Florida, United States
Northwest Georgia Oncology Centers PC
Marietta, Georgia, United States
Parkview Research Center
Fort Wayne, Indiana, United States
Dana Farber Cancer Institute
Boston, Massachusetts, United States
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, United States
Laura and Isaac Perlmutter Cancer Center
New York, New York, United States
Columbia University Medical Center
New York, New York, United States
Memorial Sloan Kettering Cancer Center
New York, New York, United States
Wake Forest Baptist Health
Winston-Salem, North Carolina, United States
Cleveland Clinic
Cleveland, Ohio, United States
Providence Health & Services
Portland, Oregon, United States
Inova Schar Cancer Institute Research
Fairfax, Virginia, United States
Countries
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References
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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.
Other Identifiers
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CDX1127-02
Identifier Type: -
Identifier Source: org_study_id