The combination of botensilimab (AGEN1181) and balstilimab (AGEN2034) has yielded promising results in patients with refractory metastatic sarcoma, showcasing durable responses and extended survival. Data from a phase 1 study (NCT03860272) presented at the 2024 ESMO Congress highlight the potential of this combination, particularly in angiosarcoma, a historically challenging subtype to treat.
Notable Efficacy in Sarcoma Subtypes
The study revealed an overall response rate (ORR) of 23% (95% CI, 13%-37%) among 52 efficacy-evaluable patients with refractory metastatic sarcoma. This included a 2% complete response rate and a 21% partial response rate. The median duration of response (DOR) was 21.7 months (95% CI, 3.4-NR), and the clinical benefit rate (CBR) at 24 weeks was 35% (95% CI, 22%-49%).
Angiosarcoma Subgroup Demonstrates Significant Response
In a subgroup of 18 patients with angiosarcoma, the ORR was 39% (95% CI, 17%-64%). Specifically, patients with cutaneous angiosarcoma (n = 9) had an ORR of 33%, while those with visceral angiosarcoma (n = 9) showed an ORR of 44%. The median DOR for the angiosarcoma subgroup was 21.7 months (95% CI, 1.9-NR), and the 24-week CBR was 44% (95% CI, 22%-69%).
Safety Profile and Future Directions
The safety profile of the combination remained consistent with previous findings. The most common immune-related toxicities were colitis and diarrhea, manageable with steroids and TNF-α–blocking therapies. No new safety signals or grade 4/5 treatment-related adverse effects were observed.
According to Breelyn Wilky, MD, director of Sarcoma Medical Oncology at the University of Colorado Medicine, further enrollment in the phase 1 expansion cohort for sarcoma is ongoing, and a phase 2 clinical trial is under consideration. Wilky noted the potential of botensilimab as a preferred immune checkpoint inhibitor for sarcomas, including traditionally difficult-to-treat, immune-cold subtypes like visceral angiosarcomas, leiomyosarcomas, and dedifferentiated liposarcomas.
Implications for Immunotherapy in Sarcoma
These findings suggest that botensilimab could broaden the applicability of immunotherapy in sarcoma, extending benefits beyond immune-hot subtypes. The ongoing research aims to confirm these results and potentially establish a new standard of care for patients with refractory metastatic sarcoma.
