A phase I/IIa study evaluating the safety, efficacy, pharmacokinetics, and pharmacodynamics of lucitanib in advanced solid tumors.
2014; Lippincott Williams & Wilkins; Volume: 32; Issue: 15_suppl Linguagem: Inglês
10.1200/jco.2014.32.15_suppl.2500
ISSN1527-7755
AutoresJean‐Charles Soria, Filippo de Braud, Ratislav Bahleda, Bárbara Adamo, Roberta Cereda, M.G. Camboni, Renata Robert, Jeffrey D. Isaacson, Jason B. Litten, Andrew R. Allen, Lindsey Rolfe, Josep Tabernero,
Tópico(s)Cancer, Hypoxia, and Metabolism
Resumo2500 Background: Lucitanib is a potent, oral inhibitor of the tyrosine kinase activity of FGFR1/2, VEGFR1-3 and PDGFRA/B. These well-described signaling pathways are essential for tumor growth, survival, migration, and angiogenesis. Further, several tumor types, including carcinoma of the breast, demonstrate amplification of FGF-related genes. Currently, there are no approved drugs for patients (pts) with molecularly defined FGF-aberrant (FGFR1 or FGF3/4/19 amplified) tumors. Methods: The first in human 3-part study is evaluating oral lucitanib monotherapy. Part 1 employed a 3+3 ascending cohort design in pts with advanced solid tumors to establish a recommended dose for further study. Parts 2 and 3 evaluated safety and efficacy of lucitanib in pts with FGF aberrant or angiogenesis sensitive tumors using continuous (part 2) or intermittent schedules (part 3) of administration. Results: 109 (part 1 n=17; part 2 n=59; part 3 n=33) pts were treated. Median age was 55 yrs [range 34-80]; 59 female; 105 stage IV; 29 breast cancer, 16 colon, 13 thyroid and 51 other tumor. Doses from 5 mg to 30 mg were evaluated with dose limiting toxicities (DLTs) dominated by VEGF-inhibition related toxicity at the 30 mg dose level. The most common adverse events (all grades, all cohorts, continuous and intermittent dosing schedules) were hypertension (86%), asthenia (73%) and proteinuria (69%). Exposure increased with dose and a t1/2 of 25-40 hours, deemed suitable for once daily administration. Clinical activity was observed at all doses tested with durable RECIST PRs in a variety of tumor types. In evaluable FGF-aberrant breast cancer pts, 50% (6 of 12) achieved RECIST PR with a median PFS of 9.4 months for all treated patients. Additionally, 1 of 3 pts with advanced squamous NSCLC experienced SD for 8 months with lucitanib therapy. Conclusions: Lucitanib demonstrated promising clinical activity and a tolerable side-effect profile in pts with advanced solid tumors, including those with FGF pathway aberrations. A phase 2 program in FGF aberrant breast and squamous NSCLC is underway in US and Europe. Clinical trial information: NCT01283945.
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