Targeting <i>FGFR1</i>-amplified lung squamous cell carcinoma with the selective pan-FGFR inhibitor BGJ398.

Abstract

8034 Background: Identifying molecular drivers in lung squamous cell carcinoma (SCC) is a major medical need since no targeted therapy is available yet for this subtype. Fibroblast growth factor receptors (FGFRs) are physiologically involved in cell proliferation and survival. Genetic alteration of FGFR genes leads to deregulated activation in various cancers, and FGFR1 amplification has been detected in lung SCC. Here, we report on patients (pts) with FGFR1-amplified lung SCC treated in a phase 1 study of BGJ398, a potent, selective pan-FGFR inhibitor. Methods: While this phase 1 dose-escalation study enrolled pts ≥ 18 years of age with any FGFR genetically altered tumor, we report here on the subgroup of pts with FGFR1-amplified advanced or metastatic lung SCC treated with 100 or 125 mg BGJ398 once daily in 28-day cycles. Pts who had progressed following at least 1 line of therapy, including platinum, were eligible for enrollment. FGFR1-amplified tumors were identified by fluorescent/chromogenic in situ hybridization (FISH/CISH) using, in most pts, a score recently established for lung SCC (Schildhaus, Mod Path 2012). Radiologic evaluation was performed every 8 weeks. Results: As of November 22, 2013, 21 pts with lung SCC were treated at the maximum tolerated dose of 125 mg/day (n = 19) or 100 mg/day (n = 2). Screening for FGFR1 amplification was most commonly performed locally (n = 17) vs centrally (n = 4) and was assayed by FISH in all but 1 case (CISH). Of 17 evaluable pts at data cutoff, 2 achieved partial responses (PR; 1 confirmed by RECIST). PRs were durable, lasting about 8 and 3 months, respectively. Of note, 2 additional pts achieved PR (1 confirmed) after the data cutoff date. Additionally, 3 pts had stable disease with tumor regressions noted (up to 11% reduction). The adverse event profile for pts in this study with lung SCC included manageable and reversible hyperphosphatemia, as well as stomatitis, alopecia, decreased appetite, and fatigue. Conclusions: Here we report on the first molecularly targeted therapy in lung SCC demonstrating clinical efficacy. These data encourage further development of BGJ398 in FGFR1-amplified lung SCC and efforts to optimize predictive biomarkers for FGFR inhibitor sensitivity. Clinical trial information: NCT01004224.