A Multicenter Randomized Phase III Trial Comparing MET Tyrosine Kinase Inhibitors vs. Immune Checkpoint Inhibitors With or Without Chemotherapy as First-Line Treatment for Patients With Advanced Non-Small Cell Lung Cancer Harboring MET Exon 14 Skipping Mutations: JCOG2506 (DECIDE-MET)
In brief
Phase III trial compares MET inhibitors with immunotherapy in 100 METex14 NSCLC patients
An open-label, multicenter randomized study will enroll 100 treatment-naïve adults with advanced MET exon 14-skipping lung cancer, assigning them to either tepotinib or capmatinib versus pembrolizumab alone (PD-L1 at least 50%) or pembrolizumab plus chemotherapy (PD-L1 <50%). Overall survival is the primary endpoint, aiming to resolve which first-line strategy offers better efficacy and tolerability.
- Journal
- Clinical lung cancer (Q1)
- Published
- 20 August 2026
- Study design
- Randomized controlled trial
- Evidence level
- Level 1, High (CEBM 1b)
- Authors
- Noriko Mitome, Kei Kunimasa, Shogo Nomura, Kota Kawabata, Ken Masuda, Yoshimasa Shiraishi, et al.
- PMID
- 42753422
- DOI
- 10.1016/j.cllc.2026.08.008
Why clinicians should know about it
- Picked for Pulmonary and Respiratory Medicine (top studies of the week, 20 September 2026): Phase III trial MET TKIs vs ICI in advanced NSCLC
- Picked for Oncology and Radiation Oncology (top studies of the week, 20 September 2026): Phase III MET‑TKI vs ICI trial in METex14 NSCLC
- Picked for Radiation Oncology (top studies of the week, 20 September 2026): MET‑TKI vs ICI trial in NSCLC, no radiotherapy arm
- Picked for Surgical Oncology (top studies of the week, 20 September 2026): MET‑TKI vs ICI trial in METex14 NSCLC
Abstract
BACKGROUND: MET exon 14 skipping (METex14) mutations represent a rare subset of non-small cell lung cancer (NSCLC) for which MET tyrosine kinase inhibitors (MET-TKIs) are recommended as first-line therapy. Patients with METex14-mutant NSCLC are often older and frequently exhibit high programmed death-ligand 1 (PD-L1) expression, providing a rationale for considering immune checkpoint inhibitor (ICI)-based therapy. Retrospective studies indicate that ICI-based therapy may offer survival outcomes comparable to, or potentially exceed those of, MET-TKIs, with possible tolerability advantages. However, without direct comparisons, it remains unclear which treatment offers more favorable outcomes in this population. PATIENTS AND METHODS: This is an open-label, multicenter, randomized phase III trial to evaluate the efficacy of ICI-based therapy compared with MET-TKIs for overall survival (OS) in patients with previously untreated advanced METex14-mutant NSCLC. Eligible patients are randomly assigned in a 1:1 ratio to receive either MET-TKIs (tepotinib or capmatinib) or ICI-based therapy, consisting of pembrolizumab monotherapy for patients with PD-L1 tumor proportion score (TPS) ≥ 50% or pembrolizumab plus platinum-based chemotherapy for those with PD-L1 TPS < 50%. The primary endpoint is OS, with secondary endpoints including progression-free survival, objective response rate, duration of response, adverse events, and quality of life. Enrollment of 100 patients is planned over 4 years. The trial was initiated in June 2026 and registered in the Japan Registry of Clinical Trials (study number: jRCT1031260225). CONCLUSION: This trial aims to provide evidence to inform optimal first-line treatment strategies for advanced METex14-mutant NSCLC and to address an evidence gap in this rare population.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.