FORT1: Phase II/III Study of Rogaratinib vs Chemotherapy in Locally Advanced/Metastatic Urothelial Carcinoma Selected Based on FGFR1/3 mRNA Expression

鈥� An ASCO Reading Room selection

December 5, 2022

Cora N. Sternberg, MD; Daniel P. Petrylak, MD; Joaquim Bellmunt, MD; Hiroyuki Nishiyama, MD; Andrea Necchi, MD; Howard Gurney, MBBS; Jae-Lyun Lee, MD; Michiel S. van der Heijden, MD; Eli Rosenbaum, MD; Nicolas Penel, MD; See-Tong Pang, MD; Jian-Ri Li, MD; Xavier Garc铆a del Muro, MD; Florence Joly, MD; Zsuzsanna P谩pai, MD; Weichao Bao, PhD; Peter Ellinghaus, PhD; Chengxing Lu, PhD; Mitchell Sierecki, MD; Sabine Coppieters, MD; Keiko Nakajima, MD; Tatiane Cristine Ishida, MD; and David I. Quinn, MBBS, PhD

Journal of Clinical Oncology

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Purpose

Rogaratinib, an oral pan-fibroblast growth factor receptor (FGFR1-4) inhibitor, showed promising phase I efficacy and safety in patients with advanced urothelial carcinoma (UC) with FGFR1-3 mRNA overexpression. We assessed rogaratinib efficacy and safety versus chemotherapy in patients with FGFR mRNA-positive advanced/metastatic UC previously treated with platinum chemotherapy.

Methods

FORT-1 (ClinicalTrials.gov identifier: ) was a phase II/III, randomized, open-label trial. Patients with FGFR1/3 mRNA-positive locally advanced or metastatic UC with ≥ 1 prior platinum-containing regimen were randomly assigned (1:1) to rogaratinib (800 mg orally twice daily, 3-week cycles; n = 87) or chemotherapy (docetaxel 75 mg/m², paclitaxel 175 mg/m², or vinflunine 320 mg/m² intravenously once every 3 weeks; n = 88). The primary end point was overall survival, with objective response rate (ORR) analysis planned following phase II accrual. Because of comparable efficacy between treatments, enrollment was stopped before progression to phase III; a full interim analysis of phase II was completed.

Results

ORRs were 20.7% (rogaratinib 18/87, 95% CI 12.7-30.7) and 19.3% (chemotherapy 17/88, 95% CI 11.7-29.1). Median overall survival was 8.3 months (95% CI 6.5 to not estimable) and 9.8 months (95% CI 6.8 to not estimable, hazard ratio 1.11, 95% CI 0.71-1.72; P=0.67). Grade 3/4 events occurred in 37 (43.0%)/4 (4.7%) patients and 32 (39.0%)/15 (18.3%), respectively. No rogaratinib-related deaths occurred. Exploratory analysis of patients with FGFR3 DNA alterations showed ORRs of 52.4% (11/21, 95% CI 29.8-74.3) for rogaratinib and 26.7% (4/15, 95% CI 7.8-55.1) for chemotherapy.

Conclusion

To our knowledge, these are the first data to compare FGFR-directed therapy with chemotherapy in patients with FGFR-altered UC, showing comparable efficacy and manageable safety. Exploratory testing suggested FGFR3 DNA alterations in association with FGFR1/3 mRNA overexpression may be better predictors of rogaratinib response.

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FORT1: Phase II/III Study of Rogaratinib vs Chemotherapy in Locally Advanced/Metastatic Urothelial Carcinoma Selected Based on FGFR1/3 mRNA Expression

Primary Source

Journal of Clinical Oncology

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