P1, N=120, Not yet recruiting, Shanghai EpimAb Biotherapeutics Co., Ltd.

To the best of our knowledge, this study represents the first evaluation of vinorelbine plus firmonertinib in EGFR-mutated locally advanced or metastatic NSCLC with M1c2 disease or elevated PD-L1 expression, aiming to provide an effective, tolerable, and convenient all-oral treatment option for this refractory population. The study protocol (version 1.2; July 18, 2025) was registered on October 24, 2025, at the Chinese Clinical Trial Registry (ChiCTR2500111096).

P1/2, N=12, Completed, Janssen Research & Development, LLC | Active, not recruiting --> Completed

P3, N=412, Active, not recruiting, Hutchison Medipharma Limited | Trial completion date: Aug 2026 --> May 2028 | Trial primary completion date: Aug 2026 --> May 2028

P2, N=145, Completed, Beijing Pearl Biotechnology Limited Liability Company | Trial completion date: Dec 2025 --> Jun 2025 | Active, not recruiting --> Completed

P2, N=66, Recruiting, SWOG Cancer Research Network | Trial completion date: May 2027 --> Jun 2028 | Trial primary completion date: May 2026 --> Jun 2027

P2, N=68, Active, not recruiting, Janssen Research & Development, LLC | Trial completion date: Jul 2026 --> Mar 2027

P1, N=16, Recruiting, Memorial Sloan Kettering Cancer Center

P=N/A, N=44, Recruiting, Novartis Pharmaceuticals | N=250 --> 44

Savolitinib monotherapy showed encouraging antitumor activities and a tolerable safety profile in heavily treated, later-line METamp G/GEJ cancers, supporting further investigation in randomized controlled trials. ClinicalTrials.gov identifier: NCT04923932 .

Detection was carried out by multiple reaction monitoring mode using the transitions m/z 634.3→184.2 for golvatinib and m/z 650.3→200.2 for golvatinib N-oxide. Further study demonstrated that CYP3A4 was the principal enzyme involved in metabolizing golvatinib. To the best of our knowledge, this is the first report combining ultra-high-performance liquid chromatography-tandem MS (UHPLC-MS/MS) with UHPLC-Quadrupole-Orbitrap-HRMS for profiling golvatinib metabolism in vitro, thereby laying a foundation for subsequent pharmacokinetic study.

Following discontinuation of Savolitinib due to drug-induced liver injury, Tislelizumab, previously associated with resistance, was reintroduced as a "rechallenge" successfully re-establishing disease control. Coupled with a systematic review of pertinent literature, this article explores the clinical features, therapeutic challenges, potential resistance mechanisms, and management approaches for such patients. It also outlines future research avenues for combination or sequential therapies, aiming to furnish a more holistic reference for clinical decision-making.