Preliminary results from a randomized, open-label, phase 2 study of botensilimab (BOT) with or without balstilimab (BAL) in refractory microsatellite stable metastatic colorectal cancer with no liver metastases (MSS mCRC NLM).

• DOI: 10.1200/jco.2025.43.4_suppl.23
• Publication Date: 2025-01-27T14:30:16Z
• Authors: Marwan Fakih; Neil Howard Segal; Benjamin L. Schle...; Thierry Andre; Filippo Pietrantonio; Benny Johnson; Alexander Vasilyev; Smitha S. Krishna...; Salvatore Siena; Wells A. Messersmith; Virgilio Souza E ...; Andrew Scott Paulson; Elena Elez; Cathy Eng; Sabine Tejpar; Michel Pierre Duc...; Wei Wu; Joseph Elan Grossman; Eric Van Cutsem; Manuel Hidalgo
• Keywords: Refractory (planetary science); Microsatellite Instability; Regorafenib

23 Background: BOT is an Fc-enhanced, multifunctional anti-CTLA−4 antibody designed to improve Fc gamma receptor-mediated effector functions and extend the reach of I-O tumor types such as MSS mCRC. Here we present preliminary data from a randomized, open-label, phase 2 study in patients (pts) with mCRC NLM treated ± BAL (anti-PD−1; NCT05608044). The aimed inform dose contribution components based on primary endpoint objective response rate (ORR) by RECIST 1.1 per investigator, safety, was not powered for statistical comparisons between arms. Methods: A total 234 pts (intent-to-treat [ITT]) were randomized (up 4 doses) 75 or 150 mg every 6 wks (Q6W), Q6W plus 240 Q2W years), standard care (SOC; regorafenib trifluridine/tipiracil). Results: Median age 58 yrs (range 23—90), 50% male, 39% rectal, 44% 3L+, 43% ECOG 1, 58% KRAS mutant, 4% NRAS 83% prior bev, all and/or pMMR local testing. Key characteristics well balanced some exceptions including median time diagnosis metastatic disease entry (30 mos across arms; 45 SOC) presence peritoneal metastases (34% 42% / BAL; 27% SOC). As July 29, 2024, follow-up 9.8 mos. efficacy safety are shown (Table). Image endpoints blinded independent review, overall survival will be reported future. Grade ≥3 treatment-related adverse events (TRAEs) highest SOC followed + combination, then monotherapy, dependency. Treatment-related immune-mediated diarrhea/colitis (imDC) manageable BAL. No new signals no deaths occurred. Conclusions: met objectives informing components. Overall ORR higher vs monotherapy. less toxicity compared Consistent published data, there responses whereas most seen ongoing, similar durable observed ph1 study. These differentiated previous I-O-only combinations SOC, supporting further investigation planned global ph3 trial. Clinical trial information: NCT05608044 . BOT/240 ITT (Randomized) n=62 n=61 38 n=40 n=33 ORR, % (95% CI) 19%(10—31) 8%(3—18) 0%(0—10) 8%(2—20) 0%(0—11) Safety (Treated) n=60 n=37 n=39 n=21 Any TRAEs, n (%) 54 (87) 59 (98) 28 (76) 31 (79) 19 (90) 22 (35) 25 (42) 8 (22) 9 (23) 12 (57) IMDC, (31) (47) 13 0 (0)