Phase II of sunitinib plus nivolumab in extraskeletal myxoid chondrosarcoma: Results from the GEIS, ISG, and UCL IMMUNOSARC II Study.

Abstract

11513 Background: Extraskeletal myxoid chondrosarcoma (EMC) is an ultra-rare sarcoma, with low sensitivity to classic chemotherapy. A previous clinical trial led by our groups showed the activity of antiangiogenics (specifically pazopanib) in patients (pts) with advanced ECM. As IMMUNOSARC I master-trial exploring sunitinib (S) plus nivolumab (N) in sarcoma detected signal of activity in ECM pts, a specific cohort of ECM was designed as a phase II trial within IMMUNOSARC II (NCT03277924). Methods: Adult pts with advanced, progressing, measurable and centrally confirmed EMC were enrolled and treated with S 37.5 mg/d in the first 14 days (d), followed by S 25 mg/d, along with N 240 mg every 2 weeks up to progression or intolerance. Imaging reassessments were done every 8 weeks. The primary endpoint was 6-month(m)-PFS rate, and the statistical assumptions were obtaining a 6m-PFSR in at least 15 pts out of 22 pts, with H 0 = 50% and H 1 = 80%, (α 0.05; β 0.10) to consider the combination as promising. Results: Twenty-four pts were accrued from May 2020 to July 2024 in 9 centres from Spain, Italy and UK. Pts had a median age of 58y (42-83), with a predominance of male (M = 19/F = 5). Thirteen (54%) pts were treatment naïve and 22 (92%) pts had metastatic disease at baseline. Grade 3-4 Adverse Events (AE) occurring in > 5% of pts were: hypertension (29.2%), ALT and AST increase (16.7 and 12.5% respectively), bilirubin increase (12.5%), Lymphocytopenia (12.5%). No G4 hematologic AEs were found, with the exception of 1 pt with G4 leukopenia. With a median FU of 18 mos (8-29), among the 23 evaluable pts, 6m-PFSR was 77% with 16/23 pts free of progression at 6 mos, and a median PFS of 13.2 mos (95%CI 5.7-20.7). Median OS has not been reached and 12m-OS was 90% ( 95%CI 77-100). Two (9%) pts achieved a RECIST 1.1 partial response while 18 (82%) and 2 pts (9%) showed a stable disease and progresion as the best response respectively. Pts (6/23) previously treated with antiangiogenic had a trend to a shorter mPFS (7mos vs 13 mos, p = 0.11) and a significantly shorter OS (28 mos vs NR, p = 0.038). Conclusions: The combination of sunitinib and nivolumab has shown to be active in advanced extraskeletal myxoid chondrosarcoma. Our data suggest that using this combo in upfront lines provides a greater benefit. Clinical trial information: NCT03277924 .