Updated overall survival (OS) and genomic analysis from a single-arm phase II study of dabrafenib (D) + trametinib (T) in patients (pts) with BRAF V600E mutant (Mut) metastatic non-small cell lung cancer (NSCLC).

Abstract

9593 Background: The phase II multicenter, open label study, which evaluated efficacy and safety of D+T in pretreated (cohort B) and treatment (tx)-naive (cohort C) pts with BRAF V600E mut metastatic NSCLC. The results of the primary analysis have been reported. Here, we present an updated survival and genomic analysis data for cohorts B and C. Methods: Tx-naïve (n=36) and pretreated (n=57) pts received D 150 mg twice daily + T 2 mg daily. Primary objective: ORR, secondary objectives: PFS, DOR, OS, safety, tolerability and PK of D+T. Tumor samples were centrally tested using a NGS cancer targeted panel (Oncomine Dx Target test, ThermoFisher Scientific). KM curves and Cox regression models were used to evaluate potential associations between baseline genomic landscape and pt efficacy endpoints. Results: As of June 22, 2019, median (m) follow-up was 16.3 mo in tx-naïve pts and 16.6 mo in pretreated pts. mOS was 17.3 mo (95% CI: 12.3, 40.2; 3 yr OS: 40%) and 18.2 mo (95% CI: 14.3, 28.6; 3 yr OS: 33%) with 14/36 and 11/57 pts alive in tx naïve and pretreated pts respectively. Detailed efficacy results are presented in table. 57/62 tumor samples retrieved from 93 pts were centrally confirmed to have BRAF V600E mut; 5 non-confirmed BRAF tumors (3 pts had PR) were positive for c-MET T1010I, KRAS G12V, ALK fusion and 2 JAK3 S493C with mPFS of 13.8 mo while OS was NE due to limited data points. Eleven pts (18%) had concomitant somatic mutations and/or genetic alterations in addition to BRAF V600E mut: 4 had alterations within PI3K pathway4 had concomitant mutations at IDH1 R132X, and 3 pts had additional mutations at BRAF G466V, KRAS G13C and a cMET exon 14 skipping, respectively. Pts whose tumors had concomitant genetic alterations, particularly in PI3K pathway, showed a trend towards decreased PFS and OS. Safety profile was similar to previous reported results. Conclusions: This update of BRF113928 study reported improved and durable OS rates with combination D+T in BRAF V600E mut NSCLC pts. Co-occurring genetic alterations might influence clinical outcomes of such pts. Further validation is ongoing to corroborate current genomic findings. Clinical trial information: NCT01336634 . [Table: see text]