Abstract

3556 Background: Botensilimab (BOT) is an Fc-enhanced, multifunctional anti-CTLA-4 antibody with unique mechanisms of action. In microsatellite stable colorectal cancer (MSS CRC), previous I-O combinations have shown poorer responses in metastatic sites of disease outside of the lungs and lymph nodes, even in non-liver metastases (NLM) populations. Here we present updated efficacy data with longer follow-up from an expanded phase 1b study (NCT03860272) in patients with NLM MSS CRC treated with BOT and balstilimab (BAL; anti-PD-1). Methods: As of Nov 29, 2023, 77 patients with NLM MSS CRC (median follow-up 13.0 months [range 0.6–42.6]) with ≥6 months follow-up were included (intention to treat [ITT]; all treated); of these, 70 had ≥1 post-baseline scan (efficacy evaluable [EE]). Patients received BOT 1 or 2 mg/kg every 6 weeks (Q6W) and BAL 3 mg/kg every 2 weeks. Endpoints included RECIST 1.1 confirmed objective response rate (ORR), disease control rate (DCR), duration of response (DOR), and overall survival (OS). Results: Median age was 56 years (range 36–82), 48% male, and median prior lines of therapy was 4 (range 1–10). ORR was 22% (17/77) and DCR was 73% (56/77), with the median DOR not reached (NR; 95% CI 5.7–NR). An additional response confirmed after the data cutoff (18/77; ORR 23%), with 11/18 responses ongoing. Subgroup analyses revealed that BOT and BAL showed comparable activity (ORR 18–33%) across metastatic sites outside of the lungs, including the peritoneum, soft tissue, pleura, and the brain (Table). One responder with an occult brain metastasis experienced pseudoprogression, followed by a complete systemic response to treatment in target lung lesions. No new safety signals were observed and updated safety and translational data will be presented. Conclusions: In summary, for MSS CRC, BOT and BAL is differentiated from previous I-O combinations by producing deep and durable responses even in difficult-to-treat metastatic sites. In NLM patients, responses were observed in 18–33% of sites of disease including the peritoneum, soft tissue, pleura, and the brain. These compelling results support further investigation in the fully enrolled, randomized, global phase 2 trial in MSS CRC (NCT05608044) and a planned global phase 3 trial. Clinical trial information: NCT03860272 . [Table: see text]