VEBrant: a multicenter, phase II study of MET inhibitor vebreltinib combined with PD-1-based immunotherapy in advanced clear cell sarcoma

Clear cell sarcoma (CCS) is an ultra-rare sarcoma with no established standard systemic therapy of proven efficacy. Mesenchymal-epithelial transition factor (MET) overexpression drives CCS progression and serves as a promising therapeutic target. Vebreltinib is a highly selective MET inhibitor with potential therapeutic benefits for CCS. Additionally, given that MET and programmed cell death protein 1 (PD-1) are both downstream molecules of melanocyte transcription factor (MITF), combined MET and PD-1 inhibition may block the MITF pathway more effectively. Moreover, aberrant MET activation indirectly upregulates programmed death ligand 1 (PD-L1), causing immune escape and resistance to PD-1 inhibitors; MET inhibition may potentially reverse this resistance. Here, we describe the rationale and design of VEBrant, a multicenter, phase II study aimed to evaluate the efficacy and safety of vebreltinib combined with PD-1-based immunotherapy in advanced CCS. Thirty patients will be enrolled, with the treatment cohort receiving combination therapy of vebreltinib and PD-1 inhibitor, and a reference cohort receiving physician’s choice therapy or best supportive care. Primary endpoint is Objective Response Rate (ORR) by Simon two-stage design. This study will provide evidence for vebreltinib combined with PD-1-based immunotherapy and improve understanding of advanced CCS management.Clinical trial registration: www.clinicaltrials.gov identifier is NCT07153887.