60Phase II Trial of Pemigatinib in Combination with Atezolizumab and Bevacizumab for Advanced Cholangiocarcinoma with FGFR2 Fusion

Background

Fibroblast growth factor receptor 2 (FGFR2) fusions or rearrangements are critical drivers in approximately 10-15% of intrahepatic cholangiocarcinoma (iCCA) cases. While FGFR inhibitors have become a standard of care, their clinical benefit is often limited by modest response durations and the inevitable emergence of resistance. To improve clinical outcomes beyond what is achievable with FGFR monotherapy, this trial investigates a triplet strategy. Preclinical data suggest that FGFR inhibition could modulate the tumor microenvironment by increasing T-cell infiltration. By adding atezolizumab (anti-PD-L1) to re-activate the immune response and bevacizumab (anti-VEGF) to normalize tumor vasculature and further reduce immunosuppression, this combination aims to overcome resistance and enhance therapeutic efficacy in the second-line setting.

Methods

The primary objective is to evaluate anti-tumor activity as measured by the Objective Response Rate (ORR). Secondary objectives include assessing Progression-Free Survival (PFS), Overall Survival (OS), and evaluating the safety and tolerability of these combinations. This is an open-label Phase II study with a total target enrollment of 26 patients with advanced iCCA harboring FGFR2 fusions or rearrangements who have progressed on one prior line of systemic therapy. The study evaluates two treatment cohorts: one receiving the triplet of pemigatinib (13.5 mg daily, 14 days on/7 days off), atezolizumab (1200 mg every 3 weeks), and bevacizumab (15 mg/kg every 3 weeks), and another receiving pemigatinib plus atezolizumab without bevacizumab. This is a trial in progress. As of the latest update, the study has been activated with patients actively receiving treatment.

By addressing the limitations of current anti-FGFR therapies, this trial will determine if the addition of immune checkpoint inhibition and VEGF blockade can significantly improve the prognosis for patients with FGFR2-fusion positive cholangiocarcinoma.