TPS272 Background: The tumor microenvironment contains high levels of immunosuppressive adenosine, which binds to and activates the A2a and A2b receptors (R) on immune cells, resulting in an ineffective anti-tumor immune response. Extracellular adenosine is primarily produced by the enzyme CD73. In prostate cancer (PC), the activity of prostatic acid phosphatase produces additional adenosine. AB928 is the first clinical-stage small molecule dual antagonist of both A2aR and A2bR, which is highly potent, pharmacodynamically active, and has been well tolerated in dose escalation studies as a single agent or in combination with chemo/immunotherapy. Targeting the adenosine pathway in combination with standard of care regimens may have a more profound effect on activating and inducing sustained anti-tumor immunity. Methods: This Phase 1b/2, open-label, multi-cohort platform study will evaluate the efficacy and safety of AB928 combination therapy in participants with metastatic castrate resistant PC (mCRPC). Each cohort will independently assess AB928 plus AB122 (anti-PD-1 antibody) in combination with standard of care (SOC; enzalutamide, docetaxel) or AB928 plus AB680 (CD73 inhibitor) with or without AB122. Cohort eligibility is informed by prior treatment history. In Ph1b, up to 15 participants will receive investigational products at the single-agent recommended dose with SOC per label guidance. Provided safety and activity stopping criteria are not met, further accrual will proceed in Ph2 and, depending on treatment cohort, may involve randomization to enzalutamide or docetaxel; crossover to experimental therapy will be allowed following progression on control treatment. Investigator-assessed antitumor response (radiologic, prostate specific antigen) will follow PCWG3 criteria. Conclusions: This Ph1b/2 study is the first to target the adenosine axis using a dual A2aR/A2bR antagonist (AB928) together with a small molecule CD73 inhibitor (AB680), anti-PD-1 antibody (AB122), and SOC for mCRPC. Study enrollment is proceeding in the United States; results will be shared in upcoming scientific conferences.

249 Objectives Changes in tumor gene expression, metabolism, and energy requirements within tumor cells have been the hallmark for cancer growth and self-sufficiency. Recent studies suggest that many tumors may utilize different biochemical pathways and nutrients for survival. 18F-4-fluoro-L-glutamine (racemic) and its resolved optical isomers (2S, 4R) and (2S, 4S) were developed as PET tracers for FDG-negative tumors. Methods Cell uptake of 18F-4-fluoro-L-glutamines were incubated in 9L and 9L.C6 (gliomas) tumor cells. After incubation of tracers, cells were lysed and counted for 18F activity. Similar uptake studies were also performed in RG2 (glioma) and two transformed human cell lines: K-562 (Leukemia) and SF188-bcl-xl (glioblastoma). Xenographs were produced in F344 rats by subcutaneous injection of 9L and 9L.C6 tumor cells in each shoulder flank. Biodistribution and PET imaging studies were conducted when tumor size reached a diameter of ~1cm. Results In vitro studies showed that both transformed tumor cells displayed a high 18F-4-fluoro-L-glutamine uptake (10 % dose/100 ug protein at 120 m), comparable to that of 3H-glutamine. RG2, 9L and 9L.C6 cells showed a lower, but indisputable, 18F-4-fluoro-L-glutamine uptake (2-4 % at 120 m). Biodistribution and PET imaging studies showed the tracers localizing in tumors with a higher uptake than those of surrounding muscle and liver tissues. Conclusions Data suggests that the tumor cells may be concurrently using glucose and glutamine for energy production. The results provide further support indicating that glutamine may be used as an alternative energy source for tumor cells. 18F-4-fluoro-glutamine may serve as a novel metabolic tracer for tumor imaging