Updated efficacy and safety of entrectinib in patients (pts) with locally advanced/metastatic NTRK fusion-positive (fp) non-small cell lung cancer (NSCLC).

Abstract

9047 Background: NTRK fusions, encoding for constitutively active oncogenic tropomyosin receptor kinase proteins, are present in many solid tumors, including NSCLC. As central nervous system (CNS) metastases are common in pts with advanced NSCLC, treatments with intracranial efficacy are needed. Entrectinib, a potent CNS-active tyrosine kinase inhibitor, has previously demonstrated efficacy in pts with NTRK-fp NSCLC in an integrated analysis of three phase I/II trials (ALKA-372-001 [EudraCT, 2012-000148–88], STARTRK-1 [NCT02097810], STARTRK-2 [NCT02568267]); objective response rate (ORR) was 63.6% (14/22; data cutoff: August 31 2020). We present updated data for this cohort. Methods: Pts ≥18 years old with locally advanced/metastatic NTRK-fp tumors were enrolled and received 600 mg oral entrectinib until disease progression, toxicity, or death. At Week 4 and then every 8 weeks, tumour response was assessed by blinded independent central review (BICR) per RECIST v1.1. Co-primary endpoints were ORR and duration of response (DoR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), intracranial efficacy, and safety. Enrolment cutoff: July 2 2020; data cutoff: August 2 2021. Results: The efficacy-evaluable population included 31 pts with NTRK-fp NSCLC. Median age was 60.0 years (range 22–88); 26 pts (83.9%) had adenocarcinoma; 11 pts (35.5%) had ≥2 prior lines of systemic therapy; 18 pts (58.1%) were current or former smokers; 15 pts (48.4%) had investigator-assessed baseline CNS metastases. Median survival follow up was 21.8 months (95% CI 19.5–30.2). Entrectinib treatment showed efficacy in pts with NTRK-fp NSCLC, including those with baseline CNS metastases by investigator (Table). In pts with BICR-assessed CNS metastases, intracranial ORR was 60.0% (6/10; 95% CI 26.2–87.8), median intracranial DoR was not estimable (NE), and median intracranial PFS was 8.9 months (95% CI 5.6–NE). In the safety-evaluable population (N=35), most treatment-related adverse events (TRAEs) were Grade 1–2 and non-serious. TRAEs led to dose reduction, interruption and discontinuation in 31.4%, 28.6%, and 5.7% of pts, respectively, and no treatment-related deaths occurred. Conclusions: In line with previously reported data, treatment with entrectinib was associated with deep and durable systemic and intracranial responses in pts with advanced NTRK-fp NSCLC. Clinical trial information: EUCTR 2012-000148-88 , NCT02097810 , NCT02568267 . [Table: see text]