On January 29, 2025 Agenus Inc. (Nasdaq: AGEN), a leader in immuno-oncology, reported publication in the Journal of Clinical Oncology showcasing data from its study of botensilimab (BOT) in combination with balstilimab (BAL) in patients with relapsed/refractory (R/R) metastatic sarcomas (Press release, Agenus, JAN 29, 2025, View Source [SID1234649933]).

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These findings further reinforce the consistency of the BOT/BAL combination, which has already shown activity and a favorable safety profile across both multiple "warm and cold" tumor types, including colon cancer, lung cancer, melanoma and ovarian cancers.

Patients with advanced sarcomas face poor outcomes and have limited treatment options, underscoring the urgent need for innovative therapies. This Phase 1 study evaluated the safety and efficacy of botensilimab (BOT), an Fc-enhanced anti-CTLA-4 antibody, in combination with balstilimab (BAL), an anti-PD-1 antibody, in this challenging patient population.

"The publication in the Journal of Clinical Oncology further underscores the significant potential of botensilimab and balstilimab to address ‘cold’ tumors like certain subtypes of refractory sarcomas," said Dr. Breelyn A. Wilky, University of Colorado Cancer Center. "These findings highlight the ability of this combination to deliver meaningful clinical benefits, including durable responses and extended survival, for patients who previously had very limited treatment options."

Publication Highlights

Study Overview

This open-label multicenter trial (NCT03860272) enrolled patients across multiple sarcoma subtypes, including angiosarcoma and leiomyosarcoma—tumor types historically resistant to traditional checkpoint inhibitors. Patients were heavily pretreated with a median of three prior lines of therapy and 15% received previous PD(L)-1 therapy.
In this expansion cohort, BOT was administered intravenously at 1 mg/kg or 2 mg/kg every 6 weeks in combination with BAL at 3 mg/kg every 2 weeks for up to 2 years.
All patients were evaluable for safety and 52 patients for efficacy.
Efficacy Highlights

Durable responses were observed across immunologically "cold" soft tissue sarcoma types, including visceral angiosarcoma and leiomyosarcoma.
Overall response rate (ORR) was 19.2% for the overall study population (n=52). Among angiosarcoma patients (n=18), ORR was 27.8%, with 33.3% in visceral and 22.2% in cutaneous subtypes.
Disease control rate (DCR) was 65.4%, with a median progression-free survival (PFS) of 4.4 months and a 36% PFS rate at 6-months.
At a median follow-up of 9.1 months, median overall survival (OS) was not reached; the 12-month OS was 69%.
Median Duration of Response (DOR) of 21.7 months, underscoring durable efficacy in heavily pretreated patients.
Safety Highlights

The BOT/BAL combination was well tolerated, with a manageable safety profile consistent with earlier findings across tumor types.
The most common treatment-related adverse event (TRAE) was diarrhea/colitis (grade 3, 6.3%), generally managed successfully with early intervention using steroids and TNF-alpha inhibitors.
No Grade 4 or 5 TRAEs were reported in this cohort.
These results add to a growing body of evidence supporting the potential of botensilimab plus balstilimab to deliver meaningful, durable benefit in multiple tumor types—especially those resistant to existing checkpoint inhibitors. As this data continues to show consistency and tolerability in colon, lung, melanoma, ovarian, and now sarcoma, it strengthens the rationale for broader investigation of this combination.