Preliminary antitumor activity of COM701 in combination with COM902 and pembrolizumab in patients with MSS-CRC and liver metastases.
Authors: Manish Sharma, Anne M. Noonan, Daniel A. Vaena, Ecaterina Elena Dumbrava, Judy S. Wang, Drew W. Rasco, Kyriakos P. Papadopoulos, Aditya V. Shreenivas, Pierre Ferre, Eran Ophir, Inbal Barbiro, Gady Cojocaru, Michelle Mahler, Adeboye H. Adewoye, Manish R. Patel
Journal: Journal of Clinical Oncology (2024)

3597 Background: There is a high unmet need for the treatment of patients [pts] with metastatic microsatellite stable colorectal cancer [MSS-CRC]. We reported encouraging preliminary antitumor activity with the combination of COM701 + nivolumab in patients with MSS-CRC and liver metastases [12/22(77%)], [ORR 2/17 (12%); disease control rate [DCR] 5/17 (29%)] 1 . COM701 is a novel, 1st-in-class immune checkpoint inhibitor [ICI] that binds to PVRIG, a DNAM-1 axis member, leading to activation of T and NK-cells; COM902 is an ICI of TIGIT. Pembrolizumab is an ICI of PD-1. We hypothesized that in pts with metastatic MSS-CRC, the triple combination by inhibiting the DNAM-1 axis would demonstrate antitumor activity with a favorable safety and tolerability profile. We present encouraging preliminary results. Methods: We enrolled 20 pts with metastatic MSS-CRC who all received COM701 15 mg/kg + COM902 3 mg/kg + pembrolizumab 200 mg all IV Q3W. Primary objectives were safety/tolerability, with secondary objective of antitumor activity of the combination. Key inclusion criteria: Age ≥ 18 yrs, measurable disease, MSS by IHC or genomic testing, ≤3 prior lines including fluroropyrimidines, irinotecan, and oxaliplatin. Key exclusion criteria: prior receipt of ICI including anti-PVRIG, anti-TIGIT. Investigator assessed responses were per RECIST v1.1, safety per CTCAE v5.0. Results: Median age 57.5yrs, 11/20 [F], 15/20 [75%] pts with liver metastases. Median of 3 prior lines of therapy. Objective response rate [ORR] 1/20 [5%] pts; 7 pts with SD. Disease control rate [CR + PR + SD] 8/20 [40%]. In pts with liver mets ORR 1/15 [7%], DCR 6/15 (40%); 6/8 [75%] pts with best response ≥SD had liver mets. Treatment related AEs were reported in 11/20 [55%] pts, the majority were ≤G2 7/20 [35%] with the most frequent TRAE of 4 pts each with ≤G2 fatigue, myalgia, 4/20 pts with G3 TRAE, there were no ≥G4 TRAEs. Strong peripheral IFNɣ induction was observed after treatment. Three pts [1 PR, 2 SD] are ongoing at the time of data cut. Conclusions: The data further supports the antitumor activity of the combination of COM701 + COM902 + pembrolizumab in pts with MSS-CRC and specifically in patients with liver metastases. Of note the data further reinforces the data previously disclosed in a similar pt population of 22 pts that received COM701 + nivolumab 1 . No new safety signals are reported. Additional clinical and translational data will be presented at the conference. Data cut 01/09/2024. Reference: 1. Rasco D, Dumbrava E, Sharma M, et al659 COM701 plus nivolumab demonstrates preliminary antitumor activity and immune modulation of tumor microenvironment in patients with metastatic MSS-CRC and liver metastases. Journal for ImmunoTherapy of Cancer 2022;10:doi: 10.1136/jitc-2022-SITC2022.0659. Clinical trial information: NCT04354246 .