THE LANCET Oncology berichtet in der Ausgabe Oct 2024 Volume 25 über die Ergebnisse der Phase-2-Studie GEOMETRY mono-1 zu Capmatinib bei nicht-kleinzelligem Lungenkrebs (NSCLC) mit einer MET Exon-14-Mutation
Die Phase-2-Studie GEOMETRY mono-1 hat die langfristige Wirksamkeit von Capmatinib bei NSCLC-Patienten mit einer MET Exon-14-Mutation untersucht. Die Ergebnisse zeigen, dass Capmatinib eine gezielte Behandlungsoption für diese Patienten ist.
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Capmatinib in MET exon 14-mutated non-small-cell lung cancer: final results from the open-label, phase 2 GEOMETRY mono-1 trial
Jürgen Wolf, Maximilian Hochmair, Ji-Youn Han, Noemi Reguart, Pierre-Jean Souquet, Egbert F Smit, Sergey V Orlov, Johan Vansteenkiste, Makoto Nishio, Maja de Jonge, Wallace Akerley, Edward B Garon, Harry J M Groen, Daniel S W Tan, Takashi Seto, Garrett M Frampton, Anna Robeva, Mariana Carbini, Sylvie Le Mouhaer, Alejandro Yovine, Aislyn Boran, Claudia Bossen, Yiqun Yang, Lexiang Ji, Lauren Fairchild, Rebecca S Heist
Summary
Background Capmatinib has previously shown activity in treatment-naive and previously treated patients with nonsmall-cell lung cancer (NSCLC) and a MET exon 14-skipping mutation (METex14). Here, we report the final outcomes from the phase 2 GEOMETRY mono-1 study with an aim to provide further evidence for the activity of capmatinib.
Methods
In this non-randomised, multi-cohort, open-label, phase 2 trial conducted in 152 centres and hospitals in 25 countries, with patients treated in 95 centres in 20 countries, eligible patients (aged ≥18 years) with MET-dysregulated, EGFR wild-type, and ALK rearrangement-negative advanced NSCLC (stage IIIB/IV) and an Eastern Cooperative Oncology Group performance status of 0 or 1 were assigned to cohorts (1a, 1b, 2, 3, 4, 5a, 5b, 6 and 7) based on their MET status (METex14 or MET amplification) and previous therapy lines. Patients received capmatinib (400 mg orally twice daily) in 21-day treatment cycles. The primary endpoint was overall response rate by blinded independent central review per Response Evaluation Criteria in Solid Tumours version 1.1 and was performed on the full analysis set (all patients who received at least one dose of capmatinib). Previous reports of this study had published interim or primary data for cohorts 1–7. Here, we report the final clinical outcomes from all METex14 cohorts (4, 5b, 6, and 7) and safety from all study cohorts (1–7). The trial is registered with ClinicalTrials.gov, NCT02414139, and has been completed.
Findings
Of 373 treated patients enrolled from June 11, 2015, to March 12, 2020, 160 (97 [61%] female) patients had METex14 NSCLC and were enrolled in four cohorts: 60 treatment-naive (cohorts 5b and 7) and 100 previously treated (cohorts 4 and 6). The overall median study follow-up was 46·4 months (IQR 41·8–65·4) for the treatment-naïve patients and 66·9 months (56·7–73·9) for previously treated patients, respectively. Overall responses were recorded in 41 (68%; 95% CI 55·0–79·7) of 60 treatment-naive patients and 44 (44%; 95% CI 34·1–54·3) of 100 previously treated patients. In all 373 treated patients, the most common treatment-related adverse events were peripheral oedema (n=174; 47%), nausea (n=130; 35%), increased blood creatinine (n=78; 21%), and vomiting (n=74; 20%). Grade 3–4 serious adverse events occurred in 164 (44%) patients, dyspnoea being the most common (18 patients [5%]). Treatment-related deaths occurred in four (1%) patients (one each of cardiac arrest, hepatitis, organising pneumonia, and pneumonitis). No new safety signals were reported.
Interpretation
These long-term results support METex14 as a targetable oncogenic driver in NSCLC and add to the evidence supporting capmatinib as a targeted treatment option for treatment-naive and previously treated patients with METex14 NSCLC.
Funding
Novartis Pharmaceuticals.
Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC 4.0 license.
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