This is a Phase 1, open-label, dose-escalation and dose-expansion study to evaluate the safety, tolerability, pharmacokinetic (PK), pharmacodynamic (PD) and clinical activity of etrumadenant (AB928) in combination with zimberelimab (AB122) (an anti-PD-1 antibody) in participants with advanced malignancies.
In the dose-escalation phase, escalating doses of etrumadenant in combination with zimberelimab will be assessed in participants with advanced malignancies. Eligible participants will receive oral administration of etrumadenant as well as IV infusion of zimberelimab. The recommended Phase 2 dose (RP2D) of etrumadenant will be determined upon completion of the dose-escalation phase. In the dose-expansion phase, etrumadenant at RP2D in combination with zimberelimab may be assessed in participants with advanced clear-cell renal cell carcinoma (RCC) or metastatic castrate-resistant adenocarcinoma of the prostate (mCRPC). Overall duration of treatment will depend on how well the treatment is tolerated. Treatment may continue until unacceptable toxicity or progressive disease or other reasons specified in the protocol.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
48
Etrumadenant is an A2aR and A2bR antagonist.
Zimberelimab is a fully human anti-PD-1 monoclonal antibody.
Scottsdale Healthcare Hospitals dba HonorHealth
Scottsdale, Arizona, United States
University of California, Los Angeles
Los Angeles, California, United States
The Angeles Clinic and Research Institute
Los Angeles, California, United States
Rocky Mountain Cancer Centers (Midtown)
Denver, Colorado, United States
University of Michigan
Ann Arbor, Michigan, United States
QUEST Research Institute
Royal Oak, Michigan, United States
Carolina BioOncology Institute
Huntersville, North Carolina, United States
Prisma Health
Greenville, South Carolina, United States
Texas Oncology, P.A. - Fort Worth Cancer Center
Fort Worth, Texas, United States
Texas Oncology, P.A. - San Antonio Medical Center
San Antonio, Texas, United States
...and 5 more locations
Percentage of participants with Adverse Events
Safety will be assessed by monitoring adverse events and clinically relevant changes in Eastern Cooperative Oncology Group (ECOG) performance status, 12 lead Electrocardiogram (ECG), vital signs, physical examination and clinical laboratory results.
Time frame: From first dose date to 90 days after the last dose (approximately 3 years)
Percentage of participants who experience a Dose Limiting Toxicity
Time frame: From first study treatment administration through Day 28
Etrumadenant Peak Serum Concentration: Cmax
Time frame: Recorded at baseline (screening), during the first 4 cycles of treatment (4 months) and 30 and 90 days post last dose (approximately 7 months)
Zimberelimab Peak Serum Concentration: Cmax
Time frame: Recorded at baseline (screening), during the first 4 cycles of treatment (4 months) and 30 and 90 days post last dose (approximately 7 months)
Etrumadenant Time of Peak Concentration: Tmax
Time frame: Recorded at baseline (screening), during the first 4 cycles of treatment (4 months) and 30 and 90 days post last dose (approximately 7 months)
Zimberelimab Time of Peak Concentration: Tmax
Time frame: Recorded at baseline (screening), during the first 4 cycles of treatment (4 months) and 30 and 90 days post last dose (approximately 7 months)
Percentage of participants with anti-drug antibodies to zimberelimab
Time frame: Recorded at baseline (screening), during the first 4 cycles of treatment (4 months), at end of treatment, and 30 and 90 days post last dose (approximately 7 months)
Progression Free Survival (PFS)
PFS as determined by Investigator according to Prostate Cancer Working Group 3 (PCWG3) for prostate adenocarcinoma and per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 for all other tumor types
Time frame: From start of treatment up to the first occurrence of progressive disease or death from any cause (approximately 1-3 years)
Overall Survival (OS)
OS as determined by the Investigator according to PCWG3 for prostate adenocarcinoma and per RECIST v1.1 for all other tumor types
Time frame: From study start of treatment up to death from any cause (approximately 1-3 years)
Duration of Response (DOR)
DOR as determined by the Investigator according to PCWG3 for prostate adenocarcinoma and per RECIST v1.1 for all other tumor types
Time frame: From the date of first occurrence of a documented objective response to first documentation of disease progression or death from any cause, whichever occurs first (approximately 1-3 years)
Percentage of Participants with Disease Control
Disease Control (complete response, partial response, or stable disease) for \>6 months as determined by the Investigator per PCWG3 for prostate adenocarcinoma and per RECIST v1.1 for all other tumor types
Time frame: From study enrolment until disease progression or loss of clinical benefit (approximately 1-3 years)
Percentage of participants with Objective Response
Objective Response as determined by Investigator according to PCWG3 for prostate adenocarcinoma and per RECIST v1.1 for all other tumor types
Time frame: From study enrolment until participant discontinuation, first occurrence of progressive disease, or death from any cause, whichever occurs first (approximately 1-3 years)
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