1309P ARC-4: Efficacy and Safety of AB928 Plus Carboplatin, Pemetrexed and a PD-1 Antibody in Participants with Metastatic Non-Small Cell Lung Cancer (Mnsclc)

Adenosine, derived from the ATP released by dying cancer cells in response to chemotherapy, activates A2a and A2b receptors (R) on immune cells, resulting in an ineffective anti-tumor immune response. Adenosine receptor blockade may enhance the efficacy of chemo-immunotherapy, when co-administered. AB928, the first clinical-stage small molecule dual A2aR/A2bR antagonist, is highly potent and well tolerated in dose escalation studies in combination with chemo-immunotherapy. This combo may be of particular interest for pts with EGFR mut whose tumours make high levels of adenosine. Phase 1/1b, open-label study in patients (pts) with mNSCLC. Pts whose tumor has a genetic alteration for which targeted therapy exists must be chemo-immunotherapy naïve, ECOG PS 0-1, and have at least one measurable lesion. Two escalating doses of AB928 (75 or 150 mg PO QD) were administered with standard doses of carboplatin (C), pemetrexed (pem) and pembrolizumab. An expansion cohort of Rel/Ref EGFRmut pts was opened with AB928 150 mg + zimberelimab (AB122, anti-PD-1 antibody) with standard dose C + pem. As of 08May20, 11 pts have received AB928 in Ph 1: 75 mg (n=3), 150 mg (n=4); Ph1b: 150 mg + zimberelimab (n=4). Number of prior therapies Ph 1: 0 to 8 (median=5) expansion(median=1). Most treatment emergent AEs (TEAEs) were Grade (Gr) 1 or 2. The most common AEs (>4 pts) were anemia, neutropenia, nausea, rash, AST/ALT elevation, pyrexia, constipation, and fatigue. Two pts experienced SAEs (Gr4 thrombocytopenia [n=1], pyrexia, vomiting, rash [n=1]) that were related to AB928. Of 8 pts with post-baseline disease assessments, all demonstrated decreased size of target lesion(s). Four pts (50%) achieved a partial response: 1 treatment-naïve pt, 2 TKI-experienced EGFRmut pts (erlotinib + osimertinib [n=1], osimertinib [n=1]), and 1 pt who progressed on ipilimumab/nivolumab. AB928 did not add to the toxicity of the standard agents. Combination treatment was associated with tumor shrinkage in all evaluable pts, including responses in those with PD after TKI or immunotherapy. Expansion is ongoing in pts with EGFRmut Rel/Ref mNSCLC.