A Study of Varlilumab and Atezolizumab in Patients With Advanced Cancer
|Carcinoma, Renal Cell Kidney Diseases Kidney Neoplasms Urogenital Neoplasms Urologic Diseases Urologic Neoplasms Neoplasms by Histologic Type Neoplasms Clear-cell Metastatic Renal Cell Carcinoma Melanoma Triple Negative Breast Cancer Bladder Cancer Head and Neck Cancer Non-small Cell Lung Cancer||Drug: Combination of Varlilumab and Atezolizumab||Phase 1 Phase 2|
|Study Design:||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||A Phase l/ll, Open Label, Dose-escalation Study of Varlilumab (CDX-1127) in Combination With Atezolizumab (MPDL3280A, Anti-PD-L1) in Patients With Advanced Cancer|
- Phase l: Safety and tolerability of varlilumab in combination with atezolizumab as measured by incidence of drug related adverse events (AEs), serious drug related AEs, dose-limiting toxicities and laboratory test abnormalities. [ Time Frame: Safety follow-up is 70 days from last study drug dose. ]
- Phase ll: Objective Response Rate [ Time Frame: Evaluated every 12 weeks until treatment is discontinued or disease progression, up to 5 years. ]The Objective Response Rate is defined as the proportion of patients with Stage lll or IV renal cell carcinoma (RCC) who achieve radiographic partial or complete response (PR or CR) according to the Response Evaluation Criteria In Solid Tumors (RECIST) V1.1 guideline.
|Study Start Date:||October 2015|
|Study Completion Date:||May 22, 2017|
|Primary Completion Date:||April 2017 (Final data collection date for primary outcome measure)|
|Experimental: Varlilumab and Atezolizumab||
Drug: Combination of Varlilumab and Atezolizumab
Treatment cycles are 12 weeks each with varlilumab and atezolizumab administered every 3 weeks. During the treatment phase of the study, eligible patients will receive varlilumab for up to 3 cycles (with a 4th cycle possible following discussion with the Medical Monitor). There is no limit on the number of cycles of atezolizumab. Patients may be discontinued from receiving study treatment (atezolizumab or varlilumab) based on the results of disease assessments or if experiencing side effects that make study therapy intolerable.
Phase l Dose: The planned dose of varlilumab will be dependent on the cohort assigned at enrollment. Varlilumab doses are 0.3 mg/kg, 1 mg/kg, or 3 mg/kg. The dose of atezolizumab is 1200 mg.
Phase ll Dose: The planned varlilumab dose will be established from the outcome of the Phase l portion of the study. Patients will receive atezolizumab at a dose of 1200 mg.
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.
Atezolizumab is an engineered anti-PD-L1 antibody.
This study will evaluate the safety, tolerability and efficacy of the anti-CD27 antibody varlilumab in combination with atezolizumab.
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 1200 mg of atezolizumab. The first phase of the study will enroll up to 18 patients and test the safety profile of the combination of varlilumab and atezolizumab in patients with various tumor types and determine which dose of varlilumab will be studied in Phase ll of the study which will enroll only patients with RCC.
During Phase ll, up to 37 patients will be enrolled and receive the recommended Phase ll dose of varlilumab in combination with atezolizumab 1200 mg.
All patients enrolled in the study will be closely monitored to determine if there is a response to the treatment as well as for any side effects that may occur.
Please refer to this study by its ClinicalTrials.gov identifier: NCT02543645
|United States, California|
|University of California - San Francisco|
|San Francisco, California, United States, 94550|
|United States, Massachusetts|
|Beth Israel Deaconess Medical Center|
|Boston, Massachusetts, United States, 02215|
|United States, New York|
|Memorial Sloan Kettering Cancer Center|
|New York, New York, United States, 10065|
|United States, North Carolina|
|Duke University Medical Center|
|Durham, North Carolina, United States, 27710|