Phase III trial of infigratinib versus gemcitabine/cisplatin in adults with advanced cholangiocarcinoma with FGFR2 gene fusion or rearrangement: results and reflections on early termination of PROOF 301

Early termination limited the ability to draw definitive conclusions on the efficacy of infigratinib as first-line treatment of FGFR2-rearranged CCA. This study illustrates the challenges of powering confirmatory studies in biomarker-selected subpopulations of rare tumors and highlights the need for regulatory collaboration to develop pragmatic frameworks for assessing novel therapies in ultra-rare malignancies.