Dr Wilky on the Study of Zalifrelimab, Balstilimab, and Doxorubicin in Soft Tissue Sarcoma

Breelyn A. Wilky, MD, director, Sarcoma Medical Oncology, the Cheryl Bennett and McNeilly Family Endowed Chair in Sarcoma Research, deputy associate director, Clinical Research, University of Colorado Anschutz Medical Campus, discusses the rationale for investigating the combination of zalifrelimab (AGEN1884), balstilimab (AGEN2034), and doxorubicin in patients with advanced/metastatic soft tissue sarcoma, and early results from a phase 2 trial (NCT04028063).

Data from the study presented at the 2023 ASCO Annual Meeting showed that patients evaluable for the study’s primary end point (n = 28) experienced a 6-month progression-free survival (PFS) rate of 46.4% (95% CI, 28%-66%), and the median PFS was 24.4 weeks (95% CI, 23.4-72.9). Among all patients evaluable for efficacy (n = 30), the median overall survival was 63 weeks (95% CI, 50-120).

With the increased use of immunotherapy in other tumor types, researchers remain interested in exploring avenues to use these treatments for patients with sarcomas, Wilky begins. PD-1 and CTLA-4 inhibitors alone may only help a small fraction of patients with sarcomas because these tend to be immune-cold tumors, Wilky expands. Investigators hoped that the addition of chemotherapy with doxorubicin may convert these tumors hot, thereby improving the responses to checkpoint inhibitor therapy, she explains. Findings from the phase 2 trial demonstrated that there were patients who had considerable benefit from this therapy, including those in subtypes that may not normally be expected to respond to checkpoint inhibitors or to doxorubicin, she notes.

Additional data showed the objective response rate was 33.3% (95% CI, 17%-53%) with a disease control rate of 80% (95% CI, 61%-92%). Wilky notes that a change to the trial protocol was made halfway through the study after patients who received priming introductory cycle of immunotherapy before chemotherapy were responding well. Therefore, investigators are now trying to understand whether a priming cycle of immunotherapy is needed before using chemotherapy in patients with soft tissue sarcoma, she concludes.