Abstract OT1-1-13: A Phase 2, randomized, open-label, multicenter, safety and efficacy study of oral lucitanib in patients with metastatic breast cancer with alterations in the FGF pathway

BACKGROUND: Lucitanib is a potent, oral inhibitor of the tyrosine kinase activity of Fibroblast Growth Factor Receptors 1-3 (FGFR1-3), Vascular Endothelial Growth Factor Receptors 1-3 (VEGFR1-3) and Platelet-Derived Growth Factor Receptors A/B (PDGFRA/B). Aberrant FGF signaling, as defined as FGFR1 and/or 11q amplification, is a hallmark genomic alteration in breast cancer, observed at a combined frequency of up to 25% of patients. Breast cancer patients with measurable disease and aberrant FGF signaling treated in the ongoing Phase 1/2 clinical trial of lucitanib monotherapy experienced an ORR of 50% and a DCR of 100%. This compelling clinical activity has led to the initiation of a global clinical development program for lucitanib in breast cancer. TRIAL DESIGN: The current study is comparing PFS for doses of lucitanib (10 or 15 mg daily) in patients with FGF-aberrant metastatic breast cancer after failure of currently available standard therapies. Approximately 160 patients will be randomized 1:1 to the 10 mg and 15 mg daily dosing groups and stratified by FGF pathway alteration ( FGFR1 or 11q amplification) and prior anti-VEGF therapy (yes or no). FGFR1 and 11q (containing the FGF ligands 3, 4, and 19) amplification is determined locally for patient enrolment and confirmed by central laboratory fluorescent in situ hybridization (FISH) testing. A total of 130 PFS events provides 80% power at a 2-sided significance level of 0.05 to detect a hazard ratio of 0.60 for comparing the 10 mg and 15 mg dose groups. Secondary objectives are ORR, DoR, DCR, OS, PROs, safety and population PK. Exploratory endpoints include tissue and blood-based biomarkers that may be predictive of response or primary resistance to treatment with lucitanib. ELIGIBILITY CRITERIA: Histologically or cytologically confirmed FGF-aberrant metastatic breast cancer relapsed or refractory to approved standard available treatment. ECOG 0 or 1. Normal organ function. Patients with uncontrolled hypertension are excluded. Citation Format: Maysa Abu-Khalaf, Ingrid Mayer, Jason B Litten, Mitch Raponi, Andrew R Allen, Lajos Pusztai, Carlos L Arteaga. A Phase 2, randomized, open-label, multicenter, safety and efficacy study of oral lucitanib in patients with metastatic breast cancer with alterations in the FGF pathway [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr OT1-1-13.