Dr Somaiah on Ongoing Research With Novel Agents in Sarcomas

“[In 2024,] the first T-cell therapy was approved [for advanced synovial sarcoma]. I think that field is still nascent, and we’re going to see a lot of work in that field moving forward because there are more cellular therapies that are going to come forward in that area.”

Neeta Somaiah, MD, professor, department chair, Department of Sarcoma Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses ongoing research with novel agents that may potentially alter the sarcoma treatment paradigm.

Although chemotherapy remains highly prevalent in the sarcoma treatment paradigm, more targeted therapies have emerged and are being developed, specifically for desmoid sarcomas, Somaiah begins, highlighting ongoing work with gamma-secretase inhibitors. A phase 3 trial (NCT03785964) evaluated the gamma-secretase inhibitor nirogacestat for the treatment of desmoid sarcoma, in which patients were randomly assigned to be treated with either nirogacestat (n = 70) or placebo (n = 72). Data demonstrated that patients treated with nirogacestat experienced a significant progression-free survival benefit compared with placebo (HR, 0.29; 95% CI, 0.15-0.55; P < .001). Of note, the likelihood of being event-free at 2 years was 76% vs 44% in the nirogacestat and placebo arms, respectively.

Of note, in 2024, the FDA granted accelerated approval to afamitresgene autoleucel (afami-cel; Tecelra) for the treatment of patients with unresectable or metastatic synovial sarcoma, which was the first T-cell therapy approved for sarcoma, Somaiah says. The FDA’s decision was supported by data from cohort 1 of the phase 2 SPEARHEAD-1 trial (NCT04044768). Among patients treated with afami-cel (n = 44), the overall response rate was 43% per independent review assessment; the complete response rate was 4.5%. The median duration of response (DOR) was 6 months (95% CI, 4.6–not reached), and the 12-month DOR rate was 39%. Somaiah concludes that although the treatment landscape for sarcomas is still developing, new therapies are on the horizon, notably for patients within specific sarcoma subtypes.