1726MO - Updated efficacy and safety of botensilimab plus balstilimab in patients with refractory metastatic sarcoma from an expanded phase I study

Background

Botensilimab (BOT) is an Fc-enhanced, multifunctional anti-CTLA-4 antibody with differentiated mechanisms of action designed to extend therapy to cold/poorly immunogenic solid tumors. We present updated results from an expanded phase Ib study in refractory metastatic sarcoma treated with BOT + balstilimab (BAL; anti-PD-1; NCT03860272).

Methods

As of 22 Mar 2024, 63 patients (pts) with sarcoma were dosed with BOT 1 or 2 mg/kg every 6 wks + BAL 3 mg/kg every 2 wks; 50 of these pts were efficacy evaluable (EE) with at least one 6-wk imaging scan.

Results

Median age was 61 yrs (range 30–81), median prior lines of therapy was 3 (range 1–10), 18% progressed on prior I-O. Most common histologies were angiosarcoma (AS) and leiomyosarcoma. In EE pts (n=50), ORR was 24% (12/50; 95% CI 13–38; includes 1 uCR and 1 pt with pseudo-progression followed by a durable response), DCR 66% (33/50; 95% CI 51–79), and median DOR 8.3 mos (95% CI 1.9–not reached [NR]) with 64% responses ongoing at 6-mos and longest ongoing response at 20.8+ mos. 6-mo PFS was 37% (95% CI 23–52), median OS NR (95% CI 10.3–NR), and estimated 12-mo OS 66% (95% CI 47–79), with a median follow-up of 8.3 mos (range 1.4–35.6). In the enriched AS subgroup (visceral, n=8; cutaneous, n=8), ORR was 44% (7/16; 95% CI 20–70; includes 1 uCR), DCR 81% (13/16; 95% CI 54–96), and median DOR NR (95% CI 1.9–NR) with 80% responses ongoing at 6-mos. 6-mo PFS was 43% (95% CI 14–71), median OS NR (95% CI 4.7–NR), with a median follow-up of 5.3 mos (range 1.4–35.6). In visceral AS alone, ORR was 50% (4/8; includes 1 pt with a response after pseudo-progression; DCR 100%). Additional AS pts are enrolling and updated data will be presented. Safety profile (n=63) remains favorable and consistent with previously reported data. Any grade immune-mediated adverse events (AEs) occurred in 52% of pts, most commonly, diarrhea/colitis (38%; 11% Gr3). No Gr4 or 5 treatment-related AEs occurred.

Conclusions

BOT + BAL combination demonstrates durable responses in this diverse poorly immunogenic sarcoma population with longer follow-up and additional pts. Responses in visceral AS are noteworthy, reflecting BOT’s differentiated MOA. Trials focusing on AS and other poorly immunogenic sarcomas are planned.

Clinical trial identification

NCT03860272.

Editorial acknowledgement

Legal entity responsible for the study

Agenus Inc.

Funding

Agenus Inc.

Disclosure

B.A. Wilky: Financial Interests, Personal, Advisory Role: Adaptimmune, Adcendo, Daiichi Sankyo, Deciphera, Epizyme, Polaris, Springworks; Financial Interests, Institutional, Research Funding: Exelixis; Non-Financial Interests, Institutional, Coordinating PI: Agenus. J.C. Trent: Financial Interests, Personal, Advisory Role: Blueprint Medicines, Deciphera, Daiichi Sankyo, Eli Lilly, Epizyme, Janssen, Novartis. A.M. Tsimberidou: Financial Interests, Personal, Advisory Role: Diaccurate, VinceRx. M. Gordon: Financial Interests, Personal, Advisory Role: Agenus, Daiichi Sankyo, Deciphera, ImaginAB, RedHill Biopharma, Salarius, Tracon; Financial Interests, Personal, Leadership Role: CareMission. A.B. El-Khoueiry: Financial Interests, Personal, Advisory Role: Agenus, AstraZeneca, Bayer, Bristol Myers Squibb, Astex Pharmaceuticals, MedImmune, Merck, Pieris Pharmaceuticals, Roche; Financial Interests, Personal, Advisory Board: CytomX Therapeutics. A. Bullock: Financial Interests, Personal, Advisory Role: Exelixis, Geistlich Pharma. M. Agulnik: Financial Interests, Personal, Advisory Role: Adaptimmune, AstraZeneca, Eli Lilly, Regeneron; Financial Interests, Personal, Speaker’s Bureau: Bayer, Bristol Myers Squibb, Deciphera. D. Mahadevan: Financial Interests, Personal, Speaker’s Bureau: Caris, Guardant Health. A. Singh: Financial Interests, Personal, Stocks or ownership: AntiCancer, Certis Oncology Solution; Financial Interests, Personal, Advisory Role: Bayer, Daiichi Sankyo, Eli Lilly; Financial Interests, Personal, Speaker’s Bureau: Daiichi Sankyo, Deciphera, Eisai, Eli Lilly, MJH Life Sciences, Novartis, Scripps Health; Financial Interests, Personal, Other: Certis Oncology Solutions; Financial Interests, Personal, Other, Travel, accommodations, expenses: Daiichi Sankyo, Deciphera, Eisai, Eli Lilly, Novartis. W. Wu, M. Avagyan: Financial Interests, Personal, Full or part-time Employment: Agenus; Financial Interests, Personal, Stocks or ownership: Agenus. J.M. Patel, J. Grossman: Financial Interests, Personal, Full or part-time Employment: Agenus; Financial Interests, Personal, Stocks or ownership: Agenus; Financial Interests, Personal, Leadership Role: Agenus. S.J. O'Day: Financial Interests, Personal, Full or part-time Employment: Agenus; Financial Interests, Personal, Stocks or ownership: Agenus; Financial Interests, Personal, Leadership Role: Agenus; Financial Interests, Personal, Officer: Agenus. G. Schwartz: Financial Interests, Personal, Stocks or ownership: Bionaut Labs, GenCirg, January Therapeutics; Financial Interests, Personal, Advisory Role: Apexigen, Array BioPharma, Astex Pharmaceuticals, Bionaut Labs, Concarlo, Ellipses Pharma, Epizyme, Gencirg, January Therapeutics, Oncugenuity, OnCusp Therapeutics, PureTech, Sellas Life Sciences, Shanghai Pharma; Financial Interests, Personal, Research Funding: Astex Pharmaceuticals; Financial Interests, Personal, Sponsor/Funding, Travel, accommodations, expenses: Array BioPharma, Epizyme. R.L. Jones: Financial Interests, Personal, Advisory Board, I worked as a consultant.: Adaptimmune, Athenex, Bayer, Boehringer Ingelheim, Blueprint, Clinigen, Eisai, Epizyme, Daiichi Sankyo, Deciphera, Immunedesign, Lilly, Springworks, Tracon, Upto Date, PharmaMar, Astex, Immunicum, Karma Oncology, Merck, Mundipharma, Synox; Financial Interests, Institutional, Research Grant, Research grant for a clinical trial.: MSD. All other authors have declared no conflicts of interest.