1MO A phase IIIb study of savolitinib in patients with locally advanced or metastatic NSCLC harboring MET exon 14 mutation

Savolitinib is a potent and highly selective oral MET tyrosine-kinase inhibitor, approved in China for the treatment of NSCLC patients (pts) that have progressed following prior systemic therapy or are unable to receive chemotherapy with MET exon 14 mutation (METex14) based on the phase II study (NCT02897479). Here we report the primary analysis results from a phase IIIb confirmatory study (NCT04923945; data cut: Oct 20, 2023; follow-up: treatment-naïve ≥12 months, previously treated ≥6 months). Previously treated (≥2L) or treatment-naive (1L) pts with advanced or metastatic METex14 NSCLC were enrolled. Pts received savolitinib QD at 600 mg (≥50 kg) or 400 mg (<50 kg). The primary endpoint was ORR assessed by BIRC per RECIST 1.1. Secondary endpoints mainly included DCR, DoR, TTR, PFS and OS. For treatment-naïve pts (n=87; median age: 70 yrs; male: 58.6%; ECOG PS of 1: 81.6%; adenocarcinoma: 80.5%; PSC: 8.0%; brain metastasis: 11.5%), as assessed by BIRC, ORR was 62.1%, DCR was 92.0%; mPFS was 13.7 months and mOS was not reached with median follow-up 18.0 and 20.8 months, respectively. For previous treated pts (n=79; median age: 68.8 yrs; male: 57.0%; ECOG PS of 1: 87.3%; adenocarcinoma: 78.5%; PSC: 5.1%; brain metastasis: 26.6%), ORR was 39.2%, DCR was 92.4%; mPFS was 11.0 months and mOS was also immature with median follow-up 11.0 and 12.5 months, respectively (see details in Table). Study drug-related treatment-emergent adverse events of Grade ≥3 occurred in 100 pts (60.2%) from total 166 pts. The most common ones (≥5%) were hepatic function abnormal (16.9%), alanine aminotransferase increased (14.5%), aspartate aminotransferase increased (12.0%), gamma-glutamyltransferase increased (6.0%), and oedema peripheral (6.0%). Table: 1MOBIRC assessedTreatment-naïve n=87Previously treated n=79ORR, % (95% CI)62.1 (51.0, 72.3)39.2 (28.4, 50.9)DCR, % (95% CI)92.0 (84.1, 96.7)92.4 (84.2, 97.2)mDoR, mos (95% CI)12.5 (8.3, 15.2)11.1 (6.6, -)mTTR, mos (95% CI)1.4 (1.4, 1.5)1.6 (1.4, 2.7)mPFS, mos (95% CI)13.7 (8.5, 16.6)11.0 (8.3, 16.6) Open table in a new tab The data showed an encouraging efficacy and a tolerable safety profile of savolitinib in treatment for METex14-mutated NSCLC, offering a new standard treatment option for naïve and treated pts for this population.