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A multicenter, randomized, non-comparative, phase II study of nivolumab ± ipilimumab for patients with metastatic sarcoma (Alliance A091401): expansion cohorts and correlative analyses
Journal article   Open access   Peer reviewed

A multicenter, randomized, non-comparative, phase II study of nivolumab ± ipilimumab for patients with metastatic sarcoma (Alliance A091401): expansion cohorts and correlative analyses

Nathan D Seligson, James L Chen, Austin C Goodrich, Brian A Van Tine, Jordan D Campbell, Allison L Richards, Cristina R Antonescu, David A Liebner, Mohammed M Milhem, Howard Streicher, …
Journal for immunotherapy of cancer, Vol.12(9), e009472
09/28/2024
DOI: 10.1136/jitc-2024-009472
PMCID: PMC11440204
PMID: 39343511
url
https://doi.org/10.1136/jitc-2024-009472View
Published (Version of record) Open Access

Abstract

Background In this open-label, randomized, non-comparative, multicenter phase II study (Alliance A091401) we report on three expansion cohorts treated with nivolumab (N) with and without ipilimumab (N+I) and provide a multi-omic correlative analysis of actionable biomarkers. Methods Patients were randomized (non-comparative) to receive either N or N+I. The primary endpoint was a 6-month confirmed response rate (CRR) defined by Response Evaluation Criteria in Solid Tumors version 1.1. Secondary endpoints included treatment-related adverse events (TRAEs), progression-free survival, and overall survival. Multi-omic correlative analyses were conducted using samples from both the primary and expansion cohorts. Results A total of 66 patients were evaluated for the primary endpoint with disease including gastrointestinal stromal tumor (GIST, n=18), undifferentiated pleomorphic sarcoma (UPS, n=24), and dedifferentiated liposarcoma (DDLPS, n=24). Neither N nor N+I achieved a complete or partial response in the GIST expansion cohort. In DDLPS and UPS, the primary response endpoint of CRR was met with N+I (both 16.6%, 2/12) but not with N alone (both 8.3%, 1/12). In the GIST cohort, TRAE was higher with N+I treatment, halting enrollment as required per protocol. In a correlative analysis of patients for the expansion cohort and the original cohort (n=86), traditional biomarkers of immunotherapy response were not correlated with response in any histological subtype. Markers of genomic instability including the presence of gene fusions and increased subclonal mutations correlated with improved clinical outcomes. Conclusions This expansion cohort reaffirms the outcomes of A091401. There remains a pressing need to determine the role of and predictive biomarkers for immunotherapy in sarcoma.
 Immunotherapy Biomarkers Original Research

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