On November 17, 2022 Agenus (Nasdaq: AGEN), an immuno-oncology company with a broad pipeline targeting cancer and infectious disease, reported that expanded data from the Company’s Phase 1 study of botensilimab (Fc-enhanced anti-CTLA-4) and balstilimab (anti-PD-1) in patients with advanced sarcoma (Press release, Agenus, NOV 17, 2022, View Source [SID1234624210]). The data demonstrate that the combination offers strong durability and superior efficacy compared to what has been reported in separate trials for standard of care and other investigational therapies in sarcoma, including in sarcoma subtypes historically unresponsive to immunotherapy. The results will be presented tomorrow in an oral presentation at the Connective Tissue Oncology Society (CTOS) 2022 Annual Meeting in Vancouver, BC, Canada.

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"The superior efficacy and durable responses achieved with botensilimab and balstilimab in advanced sarcoma build on the unprecedented clinical responses we have observed with this combination in multiple cold, treatment-resistant cancers," said Steven O’Day, MD, Chief Medical Officer at Agenus. "We are advancing multiple randomized Phase 2 trials to evaluate the therapeutic potential of this agent across a range of solid tumors."

Study Design and Highlights:

A total of 13 evaluable patients with advanced sarcoma received either 1 or 2 mg/kg botensilimab every 6 weeks and 3 mg/kg balstilimab every 2 weeks.

Patient Demographics:

Heavily pre-treated, with a median of 3 prior lines of therapy
31% had received prior immunotherapy
82% had a known tumor mutation burden of less than 10 mutations per megabase
Majority were PD-L1 negative by IHC
All of these biomarkers are associated with poor response to immunotherapy.

The botensilimab/balstilimab combination produced superior responses and strong durability relative to what has been reported in separate trials for standard of care and other combinations currently in development.

Objective responses:

46% overall response rate
Other PD-(L)1 + CTLA-4 combinations in a comparable patient population achieved only 12-16% response rates1,2
69% disease control rate (complete response + partial response + stable disease)
Durability:

67% objective responses ongoing at data cut-off
Median duration of response has not been reached
Survival:

12-month overall survival of 77%
Median overall survival has not been reached
Patient Sub-Populations:

Objective response rate of 56% and disease control rate of 78% in 9 patients with angiosarcoma, including 3 of 4 patients with visceral angiosarcoma
Other PD-(L)1 + CTLA-4 combinations achieved only 20-25% response rates in patients with angiosarcoma, with no reported responses in 7 patients with visceral angiosarcoma2,3
Responses observed in additional patients with sarcoma subtypes historically resistant to immunotherapy, including liposarcoma with leiomyosarcomatous differentiation
Tolerability:

Botensilimab was well tolerated; no grade 4 or 5 treatment-related adverse events in this cohort
Safety profile similar to what has been previously reported in the Phase 1 botensilimab program, with no new immune-mediated safety signals observed
"At present, available treatments for advanced soft tissue sarcoma patients only have modest activity, and response rates for other immunotherapy combinations for most types of sarcoma are well below 20 percent," said Breelyn Wilky, MD, Principal Investigator and Director of Sarcoma Medical Oncology at the University of Colorado School of Medicine. "The clinical responses demonstrated by botensilimab and balstilimab in this study are compelling and support plans for further development of this combination in sarcoma."

Presentation Details:

Abstract Number: 1294633

Abstract Title: Results from a Phase 1a/1b Study of Botensilimab (a Novel CTLA-4 Engager) Plus Balstilimab (Anti-PD-1 Antibody) for the Treatment of Patients with Advanced Sarcomas

Presenting Author: Breelyn A. Wilky, MD, Director of Sarcoma Medical Oncology, Deputy Associate Director for Clinical Research, University of Colorado Cancer Center

The data will be presented on November 18th at 4:15 PM PDT in an oral presentation at the Connective Tissue Oncology Society (CTOS) 2022 Annual Meeting in Vancouver, BC, Canada. An archived version of the presentation will be available on the Agenus website at agenusbio.com.