This is a Phase 1/1b, multicenter, open-label, dose-escalation and dose-expansion study to evaluate the safety, tolerability, pharmacokinetic (PK), pharmacodynamic, and clinical activity of etrumadenant (AB928) in combination with carboplatin and pemetrexed, with or without an anti-PD-1 antibody (pembrolizumab or zimberelimab), in participants with non-squamous Non-Small Cell Lung Cancer (NSCLC).
In the dose-escalation phase, escalating doses of etrumadenant in combination with carboplatin and pemetrexed at standard doses (Arm A), and etrumadenant in combination with carboplatin, pemetrexed and pembrolizumab (Arm B), may be assessed in participants with advanced NSCLC. Eligible participants will receive oral administration of etrumadenant as well as IV infused carboplatin, pemetrexed, with or without pembrolizumab in this phase. The recommended dose for expansion (RDE) of etrumadenant will be determined upon completion of the dose-escalation phase. In the dose-expansion phase, zimberelimab in combination with carboplatin and pemetrexed (Arm 1), and etrumadenant at RDE in combination with carboplatin, pemetrexed, and zimberelimab (Arm 2) may be assessed in eligible NSCLC participants who harbor an EGFR mutation and have progressed on EGFR Tyrosine Kinase Inhibitor (TKI) treatment(s). 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
77
Etrumadenant is an A2aR and A2bR antagonist
Zimberelimab is a fully human anti-PD-1 monoclonal antibody
Carboplatin administered as part of standard chemotherapy regimen
Pemetrexed administered as part of standard chemotherapy regimen
Pembrolizumab is a humanized anti-PD-1 monoclonal antibody
Arizona Cancer Research Center (ACRC)
Tucson, Arizona, United States
SCRI Florida Cancer Specialists - South
Fort Myers, Florida, United States
SCRI Florida Cancer Specialists - North
Tavares, Florida, United States
SCRI Tennessee Oncology - Nashville
Nashville, Tennessee, United States
USO Texas Oncology - Dallas (Baylor Charles A. Sammons Cancer Center)
Dallas, Texas, United States
USO Virginia Cancer Specialist
Fairfax, Virginia, United States
USO Virginia Oncology Associates
Norfolk, Virginia, United States
Medical Oncology Associates/Summit Cancer Center
Spokane, Washington, United States
National University Hospital
Singapore, Singapore
National Cancer Centre Singapore
Singapore, Singapore
...and 12 more locations
Percentage of participants with Adverse Events
Time frame: From first study treatment administration until up to 90 days after the last dose (Approximately 1 year)
Percentage of participants who experience a Dose Limiting Toxicity
Time frame: From first study treatment administration through Day 21
Percentage of participants with anti-drug antibodies to zimberelimab
Time frame: Recorded at baseline (screening), during the first 4 cycles of treatment (4 months) and 30 days post last dose (i.e. in total approximately 5 months).
Plasma concentration of etrumadenant
Time frame: Recorded at baseline (screening), during the first 4 cycles of treatment (4 months) and 30 days post last dose (i.e. in total approximately 5 months).
Serum concentration of zimberelimab
Time frame: Recorded at baseline (screening), during the first 4 cycles of treatment (4 months) and 30 days post last dose (i.e. in total approximately 5 months).
Progression Free Survival (PFS)
Time frame: From start of treatment up to the first occurrence of progressive disease or death from any cause, whichever occurs first (up to approximately 3-5 years)
Duration of Response
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 (up to approximately 3-5 years)
Percentage of Participants with Disease Control (complete response, partial response, or stable disease) for >6 months
Time frame: From study enrollment until disease progression or loss of clinical benefit (up to approximately 3-5 years)
Percentage of participants with Objective Response
Time frame: From study enrollment until participant discontinuation, first occurrence of progressive disease, or death from any cause, whichever occurs first (up to approximately 3-5 years)
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