Abstract CT130: Neoadjuvant botensilimab plus balstilimab in MMR proficient and deficient early stage cancers: First results of the pan-cancer NEOASIS study

Abstract Background: Dual immune checkpoint inhibition with botensilimab (bot, Fc-enhanced anti-CTLA4) plus balstilimab (bal, anti-PD1) has shown promising efficacy across a variety of classically non-immunogenic tumors, such as mismatch-repair proficient (pMMR) colorectal cancers (CRC) and sarcomas. In the adaptive, pan-cancer, phase II NEOASIS study, we hypothesize a high rate of pathological responses to neoadjuvant bot/bal in both pMMR and MMR deficient (dMMR) tumors. Here we present the safety and efficacy data from the safety run-in cohorts of the NEOASIS study. Methods: Patients (pts) with non-metastatic solid tumors were assigned to the dMMR or pMMR safety run-in cohorts based on IHC assessment of MMR proteins and were planned for surgery within 8 weeks of start of study treatment. Each cohort consisted of 10 pts. Patients were treated with bal 450mg on D1 and D22 plus bot on D1, at a dose of 25mg for the first 5 pts and 50mg for the next 5 pts. The primary objective of the safety run-ins was safety. Secondary objectives included pathological response (≤50% residual viable tumor, RVT), major pathological response (MPR, ≤10% RVT) and pathological complete response (pCR). Results: A total of 20 pts were treated: 10 with a dMMR and 10 with a pMMR tumor. The dMMR cohort included 9 pts with CRC and 1 with duodenal cancer (25mg bot cohort). The pMMR cohort consisted of pts with triple negative breast cancer (TNBC, n=6), ER+ BC (n=2), Merkel cell carcinoma (MCC, n=1) and sarcoma (n=1). No dose-limiting toxicities occurred at either 25mg or 50mg bot doses and all pts underwent timely surgery. One grade 3 immune-related adverse event (irAE, hepatitis) was observed in the 50mg cohort. Grade 1-2 irAEs occurred in 75% of pts, with fatigue (25%), dermatitis (20%) and hypothyroidism (15%) being the most frequent. IrAEs led to omission of the second dose of bal in 2 (10%) pts. All 5 pts in the pMMR 25mg bot cohort had a pathological response including 2 pts with a pCR (MCC, TNBC) and 3 pts with an MPR (sarcoma, ER+ BC, TNBC). In the pMMR bot 50 mg cohort, 2 pts had a pathological response, both an MPR (2 TNBC). In the dMMR 25mg bot cohort, 4 pts with CRC had a pathological response, including 2 pCR, 1 MPR and 1 PR. The only pt with limited response (duodenal cancer) had suspicion of peritoneal metastases per-operatively and while biopsies revealed no RVT in these lesions, the primary tumor showed limited response. All 5 CRC pts treated with bot 50mg had a pCR. Conclusion: Data of the safety run-in of 20 pts show that neoadjuvant bot/bal was safe and did not lead to surgical delays. In addition, the observed pathological responses are encouraging and suggest a potential for neoadjuvant immunotherapy using bot/bal across tumor types, including pMMR BC and sarcoma. Accrual in efficacy baskets for both dMMR and pMMR tumors is currently ongoing at the bot 50mg dose level. Citation Format: Peter G. de Gooyer, Lauren D. van den Dungen, Marnix H. Geukes Foppen, Cecile Grootscholten, Simone Dokter, Thomas R. de Wijkerslooth, Brechtje A. Grotenhuis, Caroline A. Drukker, Winan J. van Houdt, Sara Balduzzi, John B. Haanen, José G. van den Berg, Marleen Kok, Myriam Chalabi. Neoadjuvant botensilimab plus balstilimab in MMR proficient and deficient early stage cancers: First results of the pan-cancer NEOASIS study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr CT130.