(P 234) IMMUNOSARC II MASTER TRIAL (PHASE II OF SUNITINIB AND NIVOLUMAB): RESULTS FROM THE CLEAR CELL SARCOMA (CCS) COHORT. A GEIS, ISG, AND UCL STUDY

Objective: Clear Cell Sarcoma (CCS) is an ultra-rare sarcoma driven by a specific translocation, more often EWSR1-ATF1, for which chemotherapy offers limited activity (mPFS 3 months) in retrospective series. MET inhibitors were prospectively explored, obtaining an Overall Response Rate (ORR) of 3.8%, median Progression-Free Survival (mPFS) of 4.4 months, 6-month PFS rate of 27%, and median RECIST 1.1 Overall Survival (mOS) of 9.2 months in 28 treated patients with crizotinib, and an ORR of 9%, and mPFS of 2 months in 11 patients treated with tivantinib. IMMUNOSARC-II study tested the activity of sunitinib plus nivolumab in selected sarcoma types, based on signals of activity detected in IMMUNOSARC-I (phase I/II trial). Here we present the results of the CCS cohort.

Methods: Patients aged 12-80 years, with advanced, progressive, and measurable CCS were enrolled after central pathology confirmation. Sunitinib was administered at 37.5 mg/d during the first 2 weeks, from then on at 25 mg/d along with nivolumab 240 mg every 2 weeks. Previous therapy with antiangiogenics but not with anti-PD1/PDL1 was allowed. The main endpoint was 6-month PFS rate, and it was considered H0/H1 as 25/55%. With Simon's 2-stage Minimax design, error I 0.05 and power 0.90, at least 10 out of 23 patients should be free of progression at 6 months

Results: At the time of analysis, 20 patients were evaluable for the main endpoint, 29% were still under treatment, 62% ended the treatment due to progression, and 9% due to toxicity. With a median follow-up of 12.6 months (95% CI 1.10-24.10), the 6-month PFS rate was 50% (95% CI 26-75) while the mPFS was 7.83 months (95% 1.28-14.39). From 18 patients who underwent at least one radiological assessment, the best response were 3 partial responses (17%), 11 stable disease SD (61%), and 4 progressive disease (22%). The median of OS was 17 months (95% CI 8-26).

Conclusion: This phase 2 study matched the primary end-point showing that the combination of sunitinib and nivolumab is active in CCS, and looks promising compared to past treatments deserving further investigation. Translational studies are ongoing