Clinical Responses of Botensilimab/Balstilimab in Refractory Sarcomas at ESMO 2024

Agenus Inc. (Nasdaq: AGEN), a prominent developer of innovative immunological agents for cancer treatment, presented pivotal data at the European Society for Medical Oncology (ESMO) Congress in Barcelona, Spain. The focus was on a Phase 1 trial involving botensilimab (BOT), a novel Fc-enhanced CTLA-4 inhibitor, in combination with balstilimab (BAL), an investigational PD-1 antibody. The combination demonstrated promising clinical activity in patients with refractory sarcomas, who typically have limited treatment alternatives.

Dr. Breelyn A Wilky from the University of Colorado Cancer Center highlighted the significance of these findings. She emphasized the deep and lasting responses, especially in patients with late-stage, poorly immunogenic sarcomas like visceral angiosarcoma, leiomyosarcoma, and dedifferentiated liposarcoma. These results suggest that BOT/BAL could offer extended survival and substantial clinical benefits for patients who previously had very few options.

In the study, 64 patients with relapsed or refractory sarcomas, having undergone a median of three prior therapy lines, were administered either 1 or 2 mg/kg of BOT combined with 3 mg/kg of BAL. Out of these, 52 patients were evaluated for efficacy as they had at least one post-baseline imaging scan at six weeks.

The clinical findings were notable. The overall response rate (ORR) for the entire sarcoma cohort was 23%, with a median duration of response (DOR) of 21.7 months. The 12-month overall survival (OS) rate was 69%, and the median OS had not been reached by the time of reporting. Specifically, for angiosarcoma patients, the ORR was 39%, with a median DOR of 21.7 months. The OS rate at 12 months for this subgroup was 64%.

One representative patient with visceral angiosarcoma showed a durable response that has continued for over three years without ongoing therapy. The safety profile of the BOT/BAL combination was manageable and reversible, with no new safety concerns identified.

Dr. Steven O’Day, Chief Medical Officer at Agenus, remarked on the transformative potential of botensilimab and balstilimab for patients with refractory sarcomas. He expressed optimism about the combination's ability to induce significant and durable tumor reductions in metastatic sarcoma patients, suggesting a possible redefinition of care standards for other historically immunotherapy-resistant cancers as well.

Botensilimab is an investigational human Fc-enhanced CTLA-4 blocking antibody designed to enhance both innate and adaptive anti-tumor immune responses. Its unique design allows it to extend the benefits of immunotherapy to "cold" tumors, which typically respond poorly to existing treatments. Botensilimab works by priming and activating T cells, downregulating intratumoral regulatory T cells, activating myeloid cells, and inducing long-term memory responses.

To date, approximately 1,100 patients have received botensilimab in Phase 1 and Phase 2 clinical trials. The combination of botensilimab with balstilimab has shown clinical responses across nine types of metastatic, late-line cancers.

Agenus, founded in 1994, is a leader in immuno-oncology with a comprehensive pipeline of immunological agents. The company's mission is to expand the patient populations benefiting from cancer immunotherapy through combination approaches, using a wide range of antibody therapeutics, adoptive cell therapies, and adjuvants. Agenus has extensive development capabilities, including commercial and clinical cGMP manufacturing facilities, advanced research and discovery operations, and a global clinical operations footprint. The company is headquartered in Lexington, MA.