Introduction: COM701 is a novel first-in-class Immune checkpoint inhibitor (ICI) that binds with high affinity to poliovirus receptor related immunoglobulin domain containing (PVRIG) blocking its interaction with its ligand, PVRL2 and regulating the activity of T/NK cells through the DNAM/TIGIT axis. In preclinical experiments inhibition of PVRIG alone and in combination with anti-PD1 and/or TIGIT leads to tumor growth inhibition and activation of T-cells in the microenvironment generating an antitumor response. Methods: A total of 28 pts (Arm A/B 16/12) with a variety of cancer types were enrolled. Hybrid accelerated (1st 4 dose cohorts in Arm A) and 3+3 study design (cohorts 5-8 in Arm A and all cohorts in Arm B). Patients with performance status ECOG 0-1 and advanced or metastatic solid tumors who failed standard of care tx were eligible. Prior ICIs were permissible. In Arm A pts received COM701 monotherapy 0.01, 0.03, 0.1, 0.3, 1, 3, 10mg/kg (all IV Q 3 weeks (wks)) and 20 mg/kg (IV Q 4 wks). In Arm B, pts received COM701 at 0.3, 1 or 3mg/kg plus nivolumab 360mg IV q3 wks (3 pts/dose cohort) and 3 pts received 10mg/kg plus nivolumab 480mg IV q4 wks. Treatment emergent adverse events (TEAEs) were reported per CTCAE v4.03 and responses per RECIST v1.1. Dose-limiting toxicities (DLTs) were evaluated within a 21-day or 28-day window (for 3- or 4-wks dosing schedule respectively). Data cutoff date was January 23, 2020. Results: The median number of prior anticancer therapies were: Arm A, 7 (range 2-15), Arm B, 5 (range 2-9). No DLTs have been reported in any of the dose cohorts. Tx was well tolerated with no subjects discontinuing tx due to toxicity, the most frequent TEAEs in Arm A were fatigue (46%), nausea (31%) and anxiety (23%) - all G1-2. In Arm B ≥4 pts - anemia, lower extremity edema, rash and fatigue the majority being grade 1-2 (88%). In Arms A+B: partial response (PR) + stable disease (SD) was 57% (16/28). Of note: Arm A (COM701 20mg/kg IV q4 wks): confirmed PR in a pt with primary peritoneal cancer ongoing on tx > 15 weeks. Arm B: unconfirmed PR in a pt with MSS-CRC on COM701 0.3mg/kg plus nivolumab 360mg IV q3 wks, ongoing on tx >34 wks). Overall 11/28 pts remain on study tx including 3 pts who have not reached 1st imaging assessment. Conclusion: COM701 is well tolerated as monotherapy and in combination with nivolumab in a variety of heavily pretreated pts with advanced or metastatic solid tumors. COM701 demonstrates encouraging preliminary antitumor activity with objective responses as monotherapy and in combination with nivolumab in hard to treat tumor types (primary peritoneal and MSS-CRC).

Citation Format: Ryan Sullivan, Drew Rasco, Emerson Lim, Manish Sharma, Dale Shepard, Amita Patnaik, Erika Hamilton, Gini Fleming, Kyri Papadopoulos, Adam ElNaggar, Adeboye Henry Adewoye, Bartosz Chmielowski, Ecaterina Dumbrava, Dan Vaena. COM701 demonstrates preliminary antitumor activity as monotherapy and in combination with nivolumab in patients with advanced solid tumors [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT031.