Efficacy and safety of savolitinib in Chinese patients with locally advanced or metastatic exon 14-mutated non-small cell lung cancer: final results of a confirmatory Phase 3b study.

[BACKGROUND] Savolitinib, a potent MET inhibitor, showed promising efficacy and tolerable safety in a Phase 3b confirmatory trial for the treatment of Chinese patients with non-small cell lung cancer (NSCLC) harbouring MET exon 14 (ex14)-skipping mutations. Herein, we report the final trial results.

[METHODS] This multicentre, open-label, non-randomised, confirmatory Phase 3b study at 48 Chinese hospitals used a single-arm design. Eligible patients received savolitinib 400 mg (body weight <50 kg) or 600 mg (body weight ≥50 kg). Previously treated and treatment-naïve cohorts had a once-daily dosing frequency. The primary endpoint was objective response rate (ORR) assessed by an Independent Review Committee (IRC) per Response Evaluation Criteria in Solid Tumours v1·1 criteria. The trial is registered with ClinicalTrials.gov, NCT04923945, and has been completed.

[FINDINGS] From Aug 31, 2021, to Nov 30, 2024, 166 patients were enrolled. In previously treated patients (N = 79), median follow-up was 25·1 months; IRC-assessed ORR, 42% (95% confidence interval [CI] 31%-53%); IRC-assessed median PFS, 13·7 months (95% CI 8·3-17·9), and median OS, 25·3 months (95% CI 20·5-30·5). Among treatment-naïve patients (N = 87), with a median follow-up of 34·5 months, ORR was 62% (95% CI 51%-72%); PFS, 13·7 months (95% CI 8·5-16·6); and OS, 28·3 months (95% CI 17·5-not estimated). Grade ≥3 treatment-related adverse events occurred in 62% of patients and were manageable.

[INTERPRETATION] Savolitinib demonstrated robust and durable efficacy in patients with ex14-mutated, locally advanced NSCLC with manageable safety, supporting savolitinib as a treatment option in this disease setting.

[FUNDING] HUTCHMED, AstraZeneca.