11503 Background: Clear cell sarcoma (CCS) is an ultra rare cancer with no established standard systemic therapy of proven efficacy. The c-MET pathway plays an important role in CCS, with MET overexpression frequently observed. Targeted therapy by type Ia MET inhibitor crizotinib revealed a disease control rate (DCR) at 69.2% and objective response rate (ORR) at 3.8%. Vebreltinib is a highly selective type Ib MET inhibitor with verified efficacy in solid tumor harboring MET alterations, such as NSCLC with MET amplification or overexpression. This phase II study aimed to assess the efficacy and safety of Vebreltinib for advanced CCS. Methods: Patients (pts) with histopathologically confirmed, unresectable or metastatic CCS were enrolled (NCT07153887), regardless of prior therapy except for any MET inhibitors. Eligible pts received Vebreltinib (200 mg BID) until disease progression, intolerable toxicity, or death occurs. Prior PD1/PDL1 treatment for at least 4 months without tumor reduction are allowed to continue using the same PD1/PDL1 medicine after thorough evaluation by the investigator. Evaluation of tumor response was performed every 2 months. Primary endpoints was ORR per RECIST v1.1. Secondary endpoints included DCR, PFS, OS, 12m-OSR, DoR and treatment safety. MET expression by immunohistochemistry was collected when possible. A Simon’s two-stage design was applied: if no responses were seen in the first 13 pts, the study would stop; otherwise, 14 additional pts would be enrolled (total N=27). Results: At data cutoff on January 23, 2026, 23 pts were enrolled. Median age was 29 years (range: 16–59), 47.8% were male, 91.3% had prior surgery, and 95.7% received prior systemic therapy. All had metastatic disease, primarily to lung (78.3%), lymph nodes (56.5%), and bone (30.4%). With median follow-up of 134 days and median treatment duration of 103 days, 17 pts were evaluable for response. ORR was 41.2% (7 partial responses) and DCR was 70.6% (7 PR, 5 stable disease), meeting the pre-specified threshold for stage I continuation. Median PFS was 4.14 months (95% CI: 2.3–NA); 6-month PFS rate was 42.8%. Median OS was not reached. Treatment-related adverse events (TRAEs) occurred in 87.0% of pts, mostly grade 1-2. Grade 3-4 TRAEs occurred in 21.7% (n=5; rash n=4, fever n=1). Notably, 4 pts discontinued due to grade 4 rash within 2 weeks of starting vebreltinib combined with immunotherapy. Conclusions: Vebreltinib demonstrated notable antitumor activity for advanced CCS, representing a marked improvement over existing therapeutic options. Attention should be paid to the risk of severe rash, particularly when combined with immunotherapy. Longer follow-up is required to further confirm the efficacy and safety. Clinical trial information: NCT07153887 .
Li et al. (Wed,) studied this question.