Durable response to vebreltinib in heavily pretreated MET-amplified intrahepatic cholangiocarcinoma: a case report.

Abstract

Background: MET amplification, although detected in only 2%-5% of intrahepatic cholangiocarcinomas (ICC), represents an actionable oncogenic driver. Treatment options after failure of first-line immunochemotherapy remain limited, and clinical data on vebreltinib, a novel highly selective MET inhibitor, in this molecular subset are scarce.

Case presentation: A 61-year-old woman with metastatic ICC harboring high-level MET amplification (tissue gene copy number, 26.79) experienced disease progression on first-line durvalumab plus gemcitabine/cisplatin, second-line liposomal irinotecan/fluorouracil plus lenvatinib and durvalumab, radiotherapy, and transarterial chemoembolization. Following a brief period of vebreltinib (200 mg twice daily) plus durvalumab that was interrupted by grade 4 myelosuppression, the patient continued on vebreltinib monotherapy after hematologic recovery. Restaging computed tomography demonstrated a partial response (PR), with carbohydrate antigen 19-9 normalizing (a 99.2% reduction). This response lasted over 6 months until eventual disease progression.

Conclusion: To our knowledge, this is the first report of vebreltinib monotherapy inducing a deep and durable partial response in heavily pretreated, MET-amplified ICC, with the response lasting over 6 months despite eventual disease progression. This case underscores the critical value of comprehensive molecular profiling after first-line treatment failure to identify actionable drivers such as MET amplification.