Domestic situation of pemetinib/pemetinib

The National Medical Products Administration has approved pemigatinib/Pemigatinib for the treatment of patients with a specific type of cholangiocarcinoma, namely locally advanced or metastatic cholangiocarcinoma with fibroblast growth factor receptor 2 (FGFR 2) fusion or rearrangement. These patients have often undergone at least one systemic therapy and have advanced, metastatic, or unresectable disease. After testing, it was confirmed that there was FGFR2 fusion or rearrangement in their tumors.

China’s approval was based on two clinical studies. One is the FIGHT-202 study, a Phase 2, multicenter, open-label, single-arm study designed to evaluate the safety and efficacy of pemetinib in adult patients (age ≥18 years) with previously treated, locally advanced or metastatic cholangiocarcinoma and documented FGFR2 fusion or rearrangement. The other study is a bridging study conducted in China to evaluate the safety and efficacy of pemetinib in Chinese patients with cholangiocarcinoma. The primary endpoint was overall response rate (ORR) as assessed by the Independent Radiological Review Committee (IRRC) according to RECIST V1.1.

In theFIGHT-202 study, a total of 108 subjects with FGFR2 fusions/rearrangements were enrolled and received oral 13.5 mg of pemetinib daily (started at 2 weeks in the third quarter/stopped at the first week), and the IRRC-confirmed ORR was 37.0% (95%CI: 27.94%, 46.86%), including 4 complete responses (CR). The median duration of response (DOR) was 8.08 months, with 26 (66.0%) of 40 responding patients having a response lasting ≥6 months, and 15 (37.5%) having a response lasting ≥12 months. In another study recruiting 30 efficacy-evaluable Chinese subjects, the IRRC-confirmed ORR was 50% (95% CI: 31.3%, 68.7%). The overall safety profile was similar in both studies, with most adverse events being grade 1 or 2 according to CTCAE V5.0. Pemetinib is generally well tolerated by Chinese patients with cholangiocarcinoma.

Cholangiocarcinoma is a malignant tumor originating from bile duct epithelial cells and is divided into intrahepatic or extrahepatic based on the anatomical location of origin. The incidence of cholangiocarcinoma has been gradually increasing over the past decade. Surgery is the first-line treatment for patients with resectable disease. However, most cholangiocarcinomas are in an advanced and/or metastatic state at the time of diagnosis, losing the chance of surgical resection.

For these patients, the emergence of pemetinib undoubtedly brings them new treatment options and hope. Pemetinib has a unique mechanism of action. It can interact with ATP competitively binds to FGFR, thereby inhibiting the growth and spread of tumor cells. This strong selective inhibitory effect makes pemetinib outstanding in targeting tumors with FGFR mutations, providing a new treatment strategy for patients with cholangiocarcinoma.