1919MO - Efficacy and safety of botensilimab (BOT) plus balstilimab (BAL) in patients (pts) with refractory metastatic sarcoma

Background

BOT, a multifunctional Fc-enhanced anti-CTLA-4 antibody, enhances T cell priming, activation, and memory formation, depletes intratumoral Tregs and minimizes complement fixation. BOT±BAL has shown effectiveness across a wide variety of ‘cold’/I-O–resistant solid tumors. We report results from an expanded phase Ib study in refractory metastatic sarcoma treated with BOT+BAL (NCT03860272).

Methods

Pts received BOT 1 or 2 mg/kg every 6 wks (or fixed-dose equivalent) + BAL 3 mg/kg every 2 wks. Endpoints include overall response rate (ORR), disease control rate (DCR; best response of stable disease [SD], complete [CR] or partial response [PR]), progression free survival (PFS), overall survival (OS), and safety.

Results

We report on 22 evaluable pts who started treatment by Dec 5, 2022 with at least one 6-wk scan and ≥18 wks follow-up (data cutoff: May 3, 2023). Median age was 62 (range 40–80). Most common histologies were leiomyosarcoma, angiosarcoma (including 5 visceral) and liposarcoma. Median number of prior lines was 3, 18% had failed immunotherapy and median follow-up was 6.5 mos (range 1.4–26.1). ORR by RECIST1.1 was 27% (6/22; 95% CI 11–50) and median duration of response (DOR) was not reached across multiple subtypes. Six additional pts had meaningful clinical benefit: 1 with minor early progression (followed by a deep, durable ongoing response of 108+wks; 98%); 1 with an unconfirmed CR; and 4 with SD at 24 wks (3 ongoing). DCR was 68%, 6mo PFS was 50% (95% CI 26–70), and 12-mo OS was 82% (95% CI 52–94). More than 20 additional pts have been treated, and mature efficacy and safety data along with preliminary biomarker analyses will be presented. Safety profile (N=22) remains favorable and consistent with previously reported data. Any grade treatment-related adverse events (TRAEs) occurred in 91% of pts, grade 1-2 TRAEs 77%, grade 3 TRAEs 14% and no grade 4/5 TRAEs. The only grade 3 TRAEs occurring in >1 pt was diarrhea/colitis (9%). No treatment-related deaths occurred.

Conclusions

BOT+BAL exhibits significant efficacy with durable responses in pts with poorly immunogenic, refractory sarcomas, with a manageable safety profile. The expanded phase Ib study is ongoing.

Clinical trial identification

NCT04121676.

Editorial acknowledgement

Legal entity responsible for the study

Agenus Inc.

Funding

Agenus Inc.

Disclosure

B. Wilky: Financial Interests, Personal, Advisory Board: Adaptimmune, Adcendo, Daiichi Sankyo, Deciphera, Epizyme, Polaris, Springworks; Financial Interests, Institutional, Research Funding: Exelixis; Financial Interests, Personal, Coordinating PI: Agenus. J.C. Trent: Financial Interests, Personal, Financially compensated role: Agenus; Financial Interests, Personal and Institutional, Other, Grants: Agenus, Foghorn, IDRX, Theseus; Financial Interests, Personal, Other, Clinical Trial Consulting: Blueprint, AAdi, Deciphera, Cogent, Foghorn, BI; Financial Interests, Personal, Advisory Board: AbbVie, Inhibrix. M. Gordon: Financial Interests, Institutional, Coordinating PI: Agenus. A.B. El-Khoueiry: Financial Interests, Personal, Advisory Board: Agenus, AstraZeneca, Bayer, BMS, CytomX Therapeutics, Eisai, EMD Serono, Exelixis, Gilead, Merck, Qurient, Senti, Tallac, ABL-Bio, Servier; Financial Interests, Personal and Institutional, Research Funding: Astex Pharmaceuticals, AstraZeneca, Fulgent, Auransa. A. Bullock: Financial Interests, Personal, Other, Consulting Fees: Exelixis, Panovance, Oncolytics. M. Agulnik: Financial Interests, Personal, Other, Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: BI, Deciphera, Aadi Bioscience, Blueprint Medicine, Bayer, Genzyme, Daiichi Sankyo, Eli Lilly. D. Mahadevan: Financial Interests, Personal, Other, Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Caris, Gaardant Health. J. Patel, J. Grossman, K. Rosenthal, S.J. O'Day: Financial Interests, Personal, Full or part-time Employment: Agenus. A.M. Tsimberidou: Financial Interests, Personal, Financially compensated role: OBI Pharma, Agenus, Parker Institute for Cancer Immunotherapy, Tempus, Immatics, Tvardi, Novocure, Tachyon; Financial Interests, Personal, Other, Consulting fees: VinceRx, Diaccurate, NEX-I, BrYet, Bioeclipse, Macrogenics, Avstera Therapeutics. All other authors have declared no conflicts of interest.