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Oncology
Sarcoma

Combination immunotherapy shows limited efficacy in sarcoma

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Although combination immunotherapy (nivolumab + ipilimumab) appears to be effective in certain sarcoma subtypes, it is ineffective in others, according to a study.

The Phase 2 study investigated the efficacy of nivolumab alone and in combination with ipilimumab in 66 patients with advanced gastrointestinal stromal tumor (GIST), undifferentiated pleomorphic sarcoma (UPS), and dedifferentiated liposarcoma (DDLPS). The primary endpoint was a 6-month confirmed response rate (CRR).

There was no objective response in the GIST cohort for either treatment. However, the combination therapy met the CRR endpoint in both UPS and DDLPS (16.6%), while nivolumab alone showed a lower response rate (8.3%).

Treatment-related adverse events were more frequent with the combination therapy, leading to halted enrollment in the GIST group due to safety concerns. Multi-omic analysis revealed that traditional immunotherapy biomarkers did not correlate with treatment response. Instead, markers of genomic instability, such as gene fusions and subclonal mutations, were linked to better clinical outcomes.

Reference
Seligson ND, Chen JL, Goodrich AC, et al. A multicenter, randomized, non-comparative, phase II study of nivolumab ± ipilimumab for patients with metastatic sarcoma (Alliance A091401): expansion cohorts and correlative analyses. J Immunother Cancer. 2024;12(9):e009472. doi: 10.1136/jitc-2024-009472. PMID: 39343511; PMCID: PMC11440204.

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