Abstract 1309P
Background
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.
Methods
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.
Results
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.
Conclusions
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.
Clinical trial identification
NCT03846310.
Editorial acknowledgement
Legal entity responsible for the study
Arcus Biosciences.
Funding
Arcus Biosciences.
Disclosure
A. Spira: Honoraria (self), Research grant/Funding (institution): Cytomx; Honoraria (self), Research grant/Funding (institution): amgen; Honoraria (self), Research grant/Funding (institution): novartis; Honoraria (self), Research grant/Funding (institution): Merck; Honoraria (self), Research grant/Funding (institution): AstraZeneca; Honoraria (self), Research grant/Funding (institution): Bristol-Myers Squibb; Research grant/Funding (institution): EMD Serono; Research grant/Funding (institution): Turning Point. P. Conkling: Research grant/Funding (institution): Arcus Biosciences; Research grant/Funding (institution): Janssen; Research grant/Funding (institution): Aptose; Research grant/Funding (institution): Ignyta; Research grant/Funding (institution): Bayer-Loxo; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Bristol-Myers Squibb; Research grant/Funding (institution): US Oncology Research. A. Chaudhry: Research grant/Funding (institution): Arcus Biosciences; Speaker Bureau/Expert testimony, Research grant/Funding (institution): Bayer; Advisory/Consultancy, Research grant/Funding (institution): Exelixis; Advisory/Consultancy: Astellas Pharma; Research grant/Funding (institution), Shareholder/Stockholder/Stock options: Novartis; Research grant/Funding (institution): Merck; Research grant/Funding (institution): Ipsen Bioscience; Research grant/Funding (institution): AbbVie; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Bristol-Myers Squibb; Research grant/Funding (institution): Alkernmes, Inc; 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 Medecines Corp; Research grant/Funding (institution): Genentech; Research grant/Funding (institution): Gilead; Research grant/Funding (institution): Janssen Research; Research grant/Funding (institution): Millennium Pharmaceuticals; Research grant/Funding (institution): Innocare Pharma; Research grant/Funding (institution): Amgen. D.E. Colburn: Shareholder/Stockholder/Stock options, Full/Part-time employment: Arcus Biosciences; Shareholder/Stockholder/Stock options, Full/Part-time employment: Roche/Genentech. H. Gilbert: Shareholder/Stockholder/Stock options, Full/Part-time employment: Arcus Biosciences; Full/Part-time employment: Bellicum Pharmaceuticals; Shareholder/Stockholder/Stock options, Full/Part-time employment: Roche/Genentech; Shareholder/Stockholder/Stock options: Denali Therapeutics; Shareholder/Stockholder/Stock options: Celgene; Shareholder/Stockholder/Stock options: Bristol-Myers Squibb. M. Scharville: Shareholder/Stockholder/Stock options, Full/Part-time employment: Arcus Biosciences. O. Gardner: Shareholder/Stockholder/Stock options, Full/Part-time employment: Arcus Biosciences; Shareholder/Stockholder/Stock options, Full/Part-time employment, Former: Bellicum. K. Krishnan: Shareholder/Stockholder/Stock options, Full/Part-time employment, Officer/Board of Directors: Arcus Biosciences; Full/Part-time employment, Former: Genentech/Roche; Full/Part-time employment, Former: Astex Pharmaceuticals; Full/Part-time employment, Former: Five Prime Therapeutics. M. Paoloni: Shareholder/Stockholder/Stock options, Full/Part-time employment: Arcus Biosciences; Advisory/Consultancy, Former: Eli Lilly; Advisory/Consultancy, Former: Amgen; Advisory/Consultancy, Former: Janssen. M. Johnson: Research grant/Funding (institution): Achilles Therapeutics; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Atreca; Research grant/Funding (institution): Boehringer Ingelheim; Research grant/Funding (institution): Calithera Biosciences; Research grant/Funding (institution): EMD Serono; Research grant/Funding (institution): Genentech; Research grant/Funding (institution): Glaxo Smith Kline; Research grant/Funding (institution): Gritstone Oncology; Research grant/Funding (institution): Guardant Health; Research grant/Funding (institution): Incyte; Research grant/Funding (institution): Janssen Research and Development; Research grant/Funding (institution): Lilly; Research grant/Funding (institution): Merck; Research grant/Funding (institution): Mirati Therapeutics; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Ribon Therapeutics; Research grant/Funding (institution): Sanofi-Aventis.