Wu, Yi-Long and Guarneri, Valentina and Voon, Pei Jye and Lim, Boon Khaw and Yang, Jin-Ji and Wislez, Marie and Huang, Cheng and Liam, Chong Kin and Mazieres, Julien and Tho, Lye Mun and Hayashi, Hidetoshi and Nhung, Nguyen Viet and Chia, Puey Ling and de Marinis, Filippo and Raskin, Jo and Zhou, Qinghua and Finocchiaro, Giovanna and Le, Anh Tuan and Wang, Jialei and Dooms, Christophe and Kato, Terufumi and Nadal, Ernest and Hin, How Soon and Smit, Egbert F. and Wermke, Martin and Tan, Daniel and Morise, Masahiro and O'Brate, Aurora and Adrian, Svenja and Pfeiffer, Boris M. and Stroh, Christopher and Juraeva, Dilafruz and Strotmann, Rainer and Goteti, Kosalaram and Berghoff, Karin and Ellers-Lenz, Barbara and Karachaliou, Niki and Le, Xiuning and Kim, Tae Min and INSIGHT investigators, - (2024) Tepotinib plus osimertinib in patients with EGFR-mutated non-small-cell lung cancer with MET amplification following progression on first-line osimertinib (INSIGHT 2): a multicentre, open-label, phase 2 trial. Lancet Oncology, 25 (8). pp. 989-1002. ISSN 1470-2045, DOI https://doi.org/10.1016/S1470-2045(24)00270-5.
Full text not available from this repository.Abstract
Background Patients with EGFR-mutated non-small-cell lung cancer (NSCLC) and MET amplification as a mechanism of resistance to first-line osimertinib have few treatment options. Here, we report the primary analysis of the phase 2 INSIGHT 2 study evaluating tepotinib, a highly selective MET inhibitor, combined with osimertinib in this population. Methods This open-label, phase 2 study was conducted at 179 academic centres and community clinics in 17 countries. Eligible patients were aged 18 years or older with an Eastern Cooperative Oncology Group performance status of 0 or 1 and advanced or metastatic EGFR-mutated NSCLC of any histology, with MET amplification by tissue biopsy fluorescence in-situ hybridisation (FISH; MET gene copy number of >= 5 or MET-to-CEP7 ratio of >= 2) or liquid biopsy next-generation sequencing (MET plasma gene copy number of >= 2<middle dot>3), following progression on first-line osimertinib. Patients received oral tepotinib 500 mg plus oral osimertinib 80 mg once daily. The primary endpoint was independently assessed objective response in patients with MET amplification by central FISH treated with tepotinib plus osimertinib with at least 9 months of follow-up. Safety was analysed in patients who received at least one study drug dose. This study is registered with ClinicalTrials.gov, NCT03940703 (enrolment complete). Findings Between Feb 13, 2020, and Nov 4, 2022, 128 patients (74 58%] female, 54 42%] male) were enrolled and initiated tepotinib plus osimertinib. The primary activity analysis population included 98 patients with MET amplification confirmed by central FISH, previous first-line osimertinib and at least 9 months of follow-up (median 12<middle dot>7 months IQR 9<middle dot>9-20<middle dot>3]). The confirmed objective response rate was 50<middle dot>0% (95% CI 39<middle dot>7-60<middle dot>3; 49 of 98 patients). The most common treatment-related grade 3 or worse adverse events were peripheral oedema (six 5%] of 128 patients), decreased appetite (five 4%]), prolonged electrocardiogram QT interval (five 4%]), and pneumonitis (four 3%]). Serious treatment-related adverse events were reported in 16 (13%) patients. Deaths of four (3%) patients were assessed as potentially related to either trial drug by the investigator due to pneumonitis (two 2%] patients), decreased platelet count (one 1%]), respiratory failure (one 1%]), and dyspnoea (one 1%]); one death was attributed to both pneumonitis and dyspnoea. Interpretation Tepotinib plus osimertinib showed promising activity and acceptable safety in patients with EGFR-mutated NSCLC and MET amplification as a mechanism of resistance to first-line osimertinib, suggesting a potential chemotherapy-sparing oral targeted therapy option that should be further investigated.
| Item Type: | Article |
|---|---|
| Funders: | Merck & Company (10.13039/100009945) |
| Subjects: | R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer) |
| Divisions: | Faculty of Medicine > Medicine Department |
| Depositing User: | Ms. Juhaida Abd Rahim |
| Date Deposited: | 07 Apr 2025 07:17 |
| Last Modified: | 07 Apr 2025 07:17 |
| URI: | http://eprints.um.edu.my/id/eprint/46753 |
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