Abstract 687TiP
Background
Standard of care (SOC) regimens may contribute to immunosuppression by elevating intratumoral levels of adenosine, which activates the A2a and A2b receptors (R) on immune cells. Extracellular adenosine is primarily produced by the enzyme CD73. In prostate cancer, the activity of the highly expressed protein, prostatic acid phosphatase, produces additional adenosine. AB928, which is the first clinical-stage small molecule dual antagonist of both A2aR and A2bR, is highly potent, pharmacodynamically active, and well tolerated in dose escalation studies in combination with chemo/immunotherapy. Targeting the adenosine axis in combination with SOC regimens or immunotherapy may have a more profound effect on activating and inducing sustained antitumor immunity in patients (pts) with metastatic castrate-resistant prostate cancer (mCRPC).
Trial design
This is a phase (Ph) 1b/2, open-label, multicenter platform trial to evaluate the antitumor activity and safety of AB928-based combination therapy in pts with mCRPC. Eligibility for a specific treatment arm will be informed by prior anticancer therapy. Treatment arms will independently evaluate AB928 + zimberelimab (AB122; anti-PD-1 antibody) alone or in combination with an SOC backbone (enzalutamide or docetaxel) in earlier-line pts or AB928 + AB680 (CD73 inhibitor) +/- zimberelimab in later-line pts. Treatment arms will be conducted in 2 stages: Stage 1 (Ph1b) and Stage 2 (Ph2). In Ph1b, up to 15 pts will receive investigational product(s) at the single agent recommended dose with SOC per label guidance. Provided safety and futility stopping criteria are not met, further accrual in the earlier-line arms will involve randomization to SOC alone; in the later-line arms, upfront randomization to the all-experimental regimens will continue in Ph2. Investigator-assessed antitumor response (radiologic, prostate specific antigen [PSA]) will follow PCWG3 criteria. New treatment arms may be added via protocol amendment. ARC-6 is actively recruiting in the United States, and results will be shared in upcoming scientific conferences (NCT04381832).
Clinical trial identification
NCT04381832.
Editorial acknowledgement
Legal entity responsible for the study
Arcus Biosciences.
Funding
Arcus Biosciences.
Disclosure
S.K. Subudhi: Advisory/Consultancy, Research grant/Funding (self): Janssen Oncology; Advisory/Consultancy: Polaris; Advisory/Consultancy: Dendreon; Advisory/Consultancy, Shareholder/Stockholder/Stock options: Apricity Health; Advisory/Consultancy: Amgen; Advisory/Consultancy: Bayer; Advisory/Consultancy: Exelixis; Advisory/Consultancy, Research grant/Funding (self): AstraZeneca; Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy: Dava Oncology; Advisory/Consultancy: Cancer Now; Advisory/Consultancy: MEDACorp; Honoraria (self): Parker Institute of Cancer Immunotherapy; Honoraria (self): SITC. D. Wise: Advisory/Consultancy: ScientiaCME; Advisory/Consultancy: OncLIve; Advisory/Consultancy: Foundation Medicine; Honoraria (self), Advisory/Consultancy: Best Doctors; Advisory/Consultancy: Leap Therapeutics; Advisory/Consultancy: Guidepoint Consulting; Advisory/Consultancy: GLG Consulting; Advisory/Consultancy: Silverlight; Advisory/Consultancy: Alphasights; Advisory/Consultancy: Pfizer. S.T. Liu: Advisory/Consultancy: Merck; Advisory/Consultancy: Exelixis; Advisory/Consultancy: Esai; Advisory/Consultancy: Seattle Genetics. A. Chaudhry: Speaker Bureau/Expert testimony, Research grant/Funding (institution): Bayer; Advisory/Consultancy, Research grant/Funding (institution): Exelixis; Advisory/Consultancy: Astellas Pharma; Shareholder/Stockholder/Stock options: Novartis; Research grant/Funding (institution): Arcus Biosciences; Research grant/Funding (institution): Merck; Research grant/Funding (institution): Abbvie; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): BMS; Research grant/Funding (institution): Eli Lilly; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Beigene; Research grant/Funding (institution): BerGenBio; Research grant/Funding (institution): Blueprint; Research grant/Funding (institution): Alkermes; Research grant/Funding (institution): Genentech; Research grant/Funding (institution): Gilead; Research grant/Funding (institution): Janssen; Research grant/Funding (institution): Millennium; Research grant/Funding (institution): Basilea; Research grant/Funding (institution): IunoCare; Research grant/Funding (institution): Amgen; Research grant/Funding (institution): Novartis. J. Kim: Advisory/Consultancy: Sanofi; Advisory/Consultancy: EMD Serono; Advisory/Consultancy: Voluntis; Research grant/Funding (self): Immune Design. O. Gardner: Shareholder/Stockholder/Stock options, Full/Part-time employment: Arcus Biosciences; Shareholder/Stockholder/Stock options, Full/Part-time employment: Bellicum Pharmaceuticals; Full/Part-time employment: Aduro Biotech; Shareholder/Stockholder/Stock options, Full/Part-time employment: Janssen. H. Gilbert: Shareholder/Stockholder/Stock options, Full/Part-time employment: Arcus Biosciences; Advisory/Consultancy, Full/Part-time employment: Bellicum; Shareholder/Stockholder/Stock options, Full/Part-time employment: Roche/Genentech; Shareholder/Stockholder/Stock options: Denali; Shareholder/Stockholder/Stock options: Celgene; Shareholder/Stockholder/Stock options: BMS. M. Grady: Shareholder/Stockholder/Stock options, Full/Part-time employment: Arcus Biosciences; Full/Part-time employment: Bellicum; Full/Part-time employment: Biothera. M. Paoloni: Leadership role, Shareholder/Stockholder/Stock options, Full/Part-time employment: Arcus Biosciences; Advisory/Consultancy: Eli Lilly; Advisory/Consultancy: Janssen Oncology; Advisory/Consultancy: Amgen. K. Krishnan: Leadership role, Shareholder/Stockholder/Stock options, Full/Part-time employment: Arcus Biosciences; Full/Part-time employment: Astex; Full/Part-time employment: Roche/Genentech; Full/Part-time employment: Five Prime. M. Carducci: Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Advisory/Consultancy: Medivation; Advisory/Consultancy: Astellas; Advisory/Consultancy: Roche; Advisory/Consultancy: Abbvie; Advisory/Consultancy: Foundation Medicine; Advisory/Consultancy: Merck; Research grant/Funding (institution): EMD Serono; Research grant/Funding (institution): Exelixis; Research grant/Funding (institution): Gilead; Research grant/Funding (institution): Effector; Non-remunerated activity/ies: ECOG-ACRIN.