PROOF Trial: A Multicenter, Open-Label Randomized, Phase 3 Trial of Infigratinib versus Gemcitabine plus Cisplatin in Patients with Advanced CCA with FGFR2 Gene Rearrangements

2020 Year in Review - Cholangiocarcinoma - Cholangiocarcinoma

The ongoing PROOF trial (NCT03773302) is evaluating the efficacy and safety of infigratinib versus gemcitabine plus cisplatin as frontline therapy in patients with advanced CCA harboring FGFR2 gene rearrangements.

Infigratinib (BGJ398) is a selective fibroblast growth factor receptor 1-3 (FGFR1-3) TKI that has shown promising antitumor responses in patients with relapsed/refractory CCA bearing FGFR2 alterations. In a phase 2 study (NCT02150967), infigratinib treatment resulted in confirmed overall response rate (ORR) of 26.9% (95% confidence interval [CI], 16.8%-39.1%) and median duration of response (DOR) of 5.4 months in patients with previously treated advanced CCA harboring FGFR2 fusions.1 Based on these promising results, the randomized, multicenter, open-label, phase 3 PROOF clinical trial (NCT03773302) was initiated to evaluate the efficacy and safety of infigratinib versus gemcitabine plus cisplatin as frontline therapy in patients with advanced CCA harboring FGFR2 gene rearrangements; the study design of the PROOF trial was presented at the European Society for Medical Oncology (ESMO) Virtual Congress 2020.

Study inclusion criteria included histologically or cytologically confirmed locally advanced nonresectable or metastatic CCA, documented FGFR2 gene fusions/rearrangements (by central or local laboratory), no previous systemic therapy, and Eastern Cooperative Oncology Group (ECOG) performance status 0-1. Eligible patients will be randomized 2:1 to receive oral infigratinib once daily for 21 days of a 28-day treatment cycle versus intravenous standard gemcitabine (1000 mg/m2) plus cisplatin (25 mg/m2) on days 1 and 8 of a 21-day cycle, until disease progression, intolerance, withdrawal of informed consent, or death. The study design will permit patients on the gemcitabine plus cisplatin arm to cross over to receive infigratinib on disease progression.

The primary end point is progression-free survival (PFS) as assessed by blinded independent central review (BICR); secondary end points include overall survival, PFS (investigator assessed), ORR (BICR and investigator assessed), disease control rate (BICR and investigator assessed), DOR (BICR and investigator assessed), and safety. Exploratory end points include quality of life, pharmacokinetics, and correlative genetic alterations/biomarker assessments.

Approximately 384 eligible patients are planned for study participation. Assuming a PFS HR of 0.65 between the 2 groups, 384 patients are expected to provide an approximately 90% power to demonstrate that infigratinib improves PFS versus chemotherapy at a 2-sided significance level of 0.05. An interim analysis is planned when approximately 50% of the PFS events are observed, and primary analysis after approximately 255 PFS events occur. The trial started recruitment in December 2019, with an estimated primary completion date of September 2023.

Source: Abou-Alfa G, et al. Ann Oncol. 2020;31(3_suppl). Poster 144.

Reference

  1. Javle MM, Lowery M, Shroff RT, et al. Phase II study of BGJ398 in patients with FGFR-altered advanced cholangiocarcinoma. J Clin Oncol. 2018;36:276-282.
Related Items
Key Advances in the Treatment of Patients with BTC in 2023: New Targeted Therapies, Potential Biomarkers, and Combination Strategies
2023 Year in Review - Cholangiocarcinoma published on December 31, 2023 in Cholangiocarcinoma
KEYNOTE-966: Pembrolizumab Combined With GemCis Versus GemCis Alone in Patients With BTC
2023 Year in Review - Cholangiocarcinoma published on December 31, 2023 in Cholangiocarcinoma
Post-hoc Analysis of the ABC-01, -02, and -03 Trials in Patients With Advanced eCCA
2023 Year in Review - Cholangiocarcinoma published on December 31, 2023 in Cholangiocarcinoma
Efficacy and Safety of Tinengotinib in Patients With Advanced Refractory/Relapsed CCA Who Previously Received an FGFR Inhibitor
2023 Year in Review - Cholangiocarcinoma published on December 31, 2023 in Cholangiocarcinoma
KLF5 Inhibition Reduces Tumor Growth and Sensitizes to Chemotherapy-Induced Cell Death in Experimental Models of CCA
2023 Year in Review - Cholangiocarcinoma published on December 31, 2023 in Cholangiocarcinoma
Phase 2 Trial of SHR-1316 Plus IBI310 in Patients With Advanced iCCA After Inadequate Response to First-Line Therapy
2023 Year in Review - Cholangiocarcinoma published on December 31, 2023 in Cholangiocarcinoma
Examination of Patients With CCA Treated With Novel Targeted Therapies After Extended Molecular Profiling on Liquid Biopsies
2023 Year in Review - Cholangiocarcinoma published on December 31, 2023 in Cholangiocarcinoma
Phase 2 Component of the BEER-BTC Study: Comparing Bevacizumab Plus Erlotinib Maintenance Versus Observation in Patients With Advanced BTC
2023 Year in Review - Cholangiocarcinoma published on December 31, 2023 in Cholangiocarcinoma
The DEBATE Trial: Neoadjuvant Durvalumab Plus GemCis Versus GemCis Alone for Patients With Localized BTC
2023 Year in Review - Cholangiocarcinoma published on December 31, 2023 in Cholangiocarcinoma
The Phase 2 ADJUBIL Study of Durvalumab Plus Tremelimumab With or Without Capecitabine in BTC
2023 Year in Review - Cholangiocarcinoma published on December 31, 2023 in Cholangiocarcinoma
© Amplity Health. All rights reserved.

Subscribe Today!

To sign up for our newsletter or print publications, please enter your contact information below.

I'd like to receive: