Interim Results of Phase II Study BRF113928 of Dabrafenib in BRAF V600E Mutation–positive Non-Small Cell Lung Cancer (NSCLC) Patients.

8009 Background: Activating BRAF V600E mutations in NSCLC are present in < 2% of tumors, primarily adenocarcinoma. The BRAF inhibitor dabrafenib has demonstrated clinical activity in BRAF V600 mutation–positive melanoma. Here we report interim efficacy and safety data obtained in 17 BRAF V600E–mutant NSCLC patients enrolled in dabrafenib phase II study BRF113928. Methods: Single-arm, 2-stage, phase II study in stage IV BRAF V600E mutation–positive NSCLC pts who failed at least 1 line of chemotherapy. Dabrafenib dosed at 150 mg orally twice daily. The primary endpoint was investigator-assessed overall response rate (ORR) per RECIST 1.1 criteria. Results: The median age of the 17 pts was 69 years (range, 51-77 years). Most pts (12/17) were male, all were white with adenocarcinoma, and 13 were former smokers. All pts had failed at least 1 line of prior anticancer therapy, and 5 subjects had failed ≥ 2. At the time of reporting, 11 pts remain on therapy, and 6 have stopped therapy (5 with PD and 1 due to an AE). Thirteen pts were evaluable for efficacy. The best response for these pts included 7 PRs (5 confirmed PRs), 1 SD, and 4 PD; 1 pt discontinued due to an SAE (hypersensitivity reaction) prior to response assessment (ORR, 54%). The median duration of treatment for all 17 pts is approximately 9 weeks (range, 1-69 weeks). Among the 5 pts with confirmed PRs, duration of response was 29 and 49 weeks for the 2 pts who progressed, while the remaining 3 pts were responding for 6+ to 24+ weeks. The safety of dabrafenib in NSCLC pts appears to be generally consistent with what has been previously observed. The most common AEs were decreased appetite, fatigue, asthenia, dyspnea, and nausea, mostly grade 1 or 2. Five pts (29%) had a grade 3 AE, and 1 pt (6%) had a grade 4 SAE (hemorrhage). Conclusions: Dabrafenib shows early antitumor activity in BRAF V600E mutation–positive pretreated NSCLC pts, with an ORR of 54% and with the longest duration of response of 49 weeks thus far. Dabrafenib is generally well tolerated, and the study has met the minimum response rate (≥ 3 of first 20 pts) to continue into the second stage. This study represents the first clinical evidence of BRAF as a therapeutic target in NSCLC. Clinical trial information: NCT01336634.