Photoclinic.

Background: Clear cell sarcoma (CCS) is an ultrarare sarcoma driven by a specific chromosomal translocation, most commonly the EWS RNA binding protein 1-activating transcription factor 1 fusion (EWSR1::ATF1), for which chemotherapy shows limited activity, with a median progression-free survival (PFS) of approximately 3 months in retrospective series. In the present trial, a CCS cohort was selected based on signals of activity observed in the IMMUNOSARC I phase I/II trial evaluating nivolumab in combination with sunitinib in sarcomas. Methods: Patients aged 12 to 80 years with advanced, progressive, and measurable CCSs were enrolled after central pathology review, and molecular confirmation of an EWSR1 rearrangement was required. Sunitinib was administered at 37.5 mg/d during the first 2 weeks and then at 25 mg/d along with nivolumab at 240 mg every 2 weeks. The primary end point was the 6-month PFS rate, defined under the null (H0) and alternative (H1) hypotheses as 25% and 55%, respectively. Under Simon's 2-stage minimax design (α = 0.05, power = 0.90), a minimum of 10 of 23 patients needed to be progression-free at 6 months. Results: At the time of cutoff, 23 patients were evaluable for the primary end point. With a median follow-up of 23.0 months (95% confidence interval [CI], 10.0 to 35.0 months), the 6-month PFS rate was 50.1% (95% CI, 29.1% to 71.1%), while the median PFS was 6.2 months (95% CI, 3.0 to 9.3 months). Of 21 patients who underwent at least 1 radiological assessment, 3 (14.3%) achieved partial response, 14 (66.7%) had stable disease, and 4 (19.0%) had progressive disease. The median overall survival was 17.0 months (95% CI, 95% CI, 5.6 to 28.5 months). The main all-grade drug-related toxicities were lymphocytopenia (46.2%), leukopenia (38.5%), anemia (38.5%), and neutropenia (38.5%). Two grade 4 toxicities were reported: Alanine aminotransferase increased and ischemia (each 3.8%), while 31 grade 3 toxicities occurred, with anemia and lymphocytopenia being the most common (each 23.1%). A higher programmed death-ligand 1 composite score was associated with better PFS: 21.2 months (95% CI, 6.0 to 36.4 months) versus 4.2 months (95% CI, 2.7 to 5.6 months), P = 0.045. Conclusions: While further studies are needed, initial findings suggest that nivolumab plus sunitinib could be a valuable addition to the current armamentarium for CCS management. Trial registration: ClinicalTrials.gov ID NCT03277924 (date of registration: 2017 September 6).