Date: 2014-05-31
Type of information: Presentation of results at a congress
phase: 1-2
Announcement: presentation of results at the 50th American Society of Clinical Oncology (ASCO) Annual Meeting, May 30 to June 3, 2014, in Chicago
Company: Clovis Oncology (USA)
Product: lucitanib
Action
mechanism: Lucitanib is a inhibitor of fibroblast growth factor receptor 1-3 (FGFR1-3), vascular endothelial growth factor receptors 1-3 (VEGFR1-3) and platelet-derived growth factor receptors alpha and beta (PDGFRα-β). The FGF, VEGF and PDGF cellular signaling pathways each play a role in tumor growth and angiogenesis. FGF-related genetic changes, in particular, have been described in several cancer types, including breast and squamous non-small cell lung cancer, particularly in the context of acquired resistance to initial therapies.
Disease: advanced solid tumors
Therapeutic area: Cancer - Oncology
Country:
Trial details:
Latest
news: * On May 31, 2014, Clovis Oncology announced results from an ongoing Phase 1/2a monotherapy study evaluating lucitanib, the Company’s novel, potent inhibitor of the tyrosine kinase activity of fibroblast growth factor receptors 1 through 3 (FGFR1-3), vascular endothelial growth factor receptors 1 through 3 (VEGFR1-3) and platelet-derived growth factor receptors alpha and beta (PDGFRα-β). Data from the study have been presented in an oral presentation by Professor Jean-Charles Soria at the 2014 American Society of Clinical Oncology (ASCO) Annual Meeting.Over 100 patients have been treated with lucitanib in this ongoing Phase 1/2a study. All patients treated in the dose-expansion cohorts have been identified as having FGF-aberrant or angiogenesis-sensitive solid tumors. Patients in the Phase 1 dose escalation portion of the study were treated with once-daily (QD) dosing of 5mg, 10mg, 20 mg or 30mg of lucitanib, data from which led to a recommended continuous dose of 10 to 20mg QD for the cohort-expansion phase of the study. Evidence of Activity: Objective responses have been seen at starting doses of 10, 15 and 20mg daily. In the FGF-aberrant subgroup, defined as amplification of either FGFR1 or an FGF ligand-containing amplicon (11q), six of twelve breast cancer patients achieved objective responses (50 percent), and the remaining 50 percent experienced stable disease. For these patients, median progression free survival was 9.6 months and median duration of response was 11.5 months. In the angiogenesis subgroup, most of whom had progressed on prior anti-angiogenic therapy, 26 percent (7/27) of patients with measureable disease achieved an objective response (3 Complete Responses (CRs) and 4 Partial Responses (PRs); and 56 percent (15/27) experienced stable disease. Median progression-free survival was 5.9 months in the angiogenesis sub-group and median duration of response was 7.5 months. Notably, ten patients treated in this study have maintained objective responses for greater than one year. Safety and Tolerability: Most drug-related adverse events (AEs) experienced by patients on study were mild or asymptomatic. The most common drug-related AEs observed were hypertension (75 percent), proteinuria (51 percent), asthenia (37 percent) and hypothyroidism (32 percent). Hypertension, proteinuria and hypothyroidism are thought to be a result of VEGFR2 inhibition, and represent on-target toxicities. Clovis, which holds exclusive U.S. and Japanese rights to lucitanib, is collaborating with its development partner, Les Laboratoires Servier, on the clinical development of lucitanib, initially targeting solid tumors with FGFR pathway activation, including breast cancer and squamous non-small cell lung cancer. A broad Phase 2 program is being initiated to explore lucitanib in multiple indications, including a U.S. study in patients with treatment-refractory FGF-aberrant breast cancer and a global study in patients with advanced squamous NSCLC with FGFR1 amplification. In parallel with these Clovis-sponsored studies expected to begin shortly, two Servier-sponsored studies of lucitanib in patients with advanced breast cancer are underway in Europe.
