985 Triple blockade of DNAM-1axis with COM701(anti-PVRIG)+COM902(anti-TIGIT)+Pembrolizumab shows prelim antitumor activity in pts with platinum resistant ovarian cancer, interim results of phase I trial

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Background Treatment [tx] options for platinum resistant ovarian cancer [PROC] are limited. Responses in this patient [pt] group with immune check point inhibitors [ICI], including combination with anti-TIGIT antibodies, is <10% and 10% with chemotherapy.1–3 COM701, a IgG4, potential 1stin-class ICI antibody blocks PVRIG, leading to activation of T-cells. COM902 is an IgG4 ICI blocker of TIGIT. A 20% objective response rate (ORR) following combination COM701 + BMS-986207 (anti-TIGIT) + nivolumab in PROC was previously reported.3 We present an additional cohort of PROC pts treated with COM701, COM902 and pembrolizumab demonstrating encouraging antitumor activity, and safety, consistent with the prior report.4 Methods CPG-02-101 is ongoing. The PROC cohort enrolled 25 pts by April 2024 (table 1). 25 safety-evaluable pts received COM701 15 mg/kg + COM902 3 mg/kg + pembrolizumab 200 mg Q3W. Primary objectives (obj): safety/tolerability; secondary obj: antitumor activity. Key inclusion criteria: Age ≥ 18 yrs, up to 3 prior lines of tx for histologically confirmed PROC. Key exclusion criteria: prior receipt of any ICI. Investigator assessed responses per RECIST v1.1, AE severity per CTCAE v5.0. Results As of 16 May 2024, ORR was assessed in 23 efficacy evaluable pts median (med) age, 63yr, mean time on treatment 10.6 weeks (2–22 weeks, 10 pt ongoing, figure 3). Best ORR 4/23 (17.4%) pts (1 CR, 3 PRs, table 2) and 6 pts with SD (figure 1–3), resulting in a disease control rate (CR+PR+SD) of 10/23 (43.5%, table 2). ADC treatment was given to 6 of the pts prior to enrollment on to the study. One PR pt had prior treatment with mirvetuximab soravtansine-gynx. Strong peripheral IFN-g induction was observed following treatment in 14 out of 14 pts tested. Majority of AEs were of ≤2 grade in severity. No grade 4/5 events were reported. One grade 3 event of serious immune related encephalopathy was reported in one pt, which was resolving following treatment with steroids (tables 3,4). Conclusions The combination of COM701 + COM902 + pembrolizumab demonstrates encouraging signal of antitumor activity with immune activation in pts with heavily pre-treated PROC. The study further supports the clinical utility of blocking PVRIG and TIGIT both of the DNAM -1 pathway + anti-PD1 in PROC. The trial is ongoing and updated data will be presented at the conference. Data extract 05/16/2024. Trial Registration Clinical trial identification NCT04354246. References Zhang Y, et al. Current advances in PD-1/PD-L1 blockade in recurrent epithelial ovarian cancer. Front Immunol 2022;13:901772. Perets R, et al. Safety and efficacy of vibostolimab (vibo) plus pembrolizumab (pembro) and coformulation of vibo/pembro in ovarian cancer naive to PD-1/PD-L1 inhibitors. Cancer Research 2022;82(12)(abstract CT180). Mutch DG, et al. Randomized phase III trial of gemcitabine compared with pegylated liposomal doxorubicin in patients with platinum-resistent ovarian cancer. J Clin Oncol 2007;25(19):2811. Moroney J, et al. Triple blockade of the DNAM-axis with COM701 + BMS-986207 + nivolumab demonstrates preliminary antitumor activity in patients with platinum resistant OVCA. Immuno-Oncology and Technology 2022;16(1)(abstract 158P). Ethics Approval The CPG-02-101 trial is being conducted in accordance with the ethical principles stipulated in the Declaration of Helsinki.

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