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Clinical Trial
. 2023 Sep 1;9(9):1260-1266.
doi: 10.1001/jamaoncol.2023.1962.

Tepotinib Treatment in Patients With MET Exon 14-Skipping Non-Small Cell Lung Cancer: Long-term Follow-up of the VISION Phase 2 Nonrandomized Clinical Trial

Julien Mazieres  1 , Paul K Paik  2   3 , Marina C Garassino  4   5 , Xiuning Le  6 , Hiroshi Sakai  7   8 , Remi Veillon  9 , Egbert F Smit  10   11 , Alexis B Cortot  12 , Jo Raskin  13 , Santiago Viteri  14   15 , Yi-Long Wu  16 , James C H Yang  17 , Myung-Ju Ahn  18 , Rui Ma  19 , Jun Zhao  20 , Aurora O'Brate  21 , Karin Berghoff  22 , Rolf Bruns  23 , Gordon Otto  24 , Andreas Johne  24 , Enriqueta Felip  25 , Michael Thomas  26   27
Affiliations
Clinical Trial

Tepotinib Treatment in Patients With MET Exon 14-Skipping Non-Small Cell Lung Cancer: Long-term Follow-up of the VISION Phase 2 Nonrandomized Clinical Trial

Julien Mazieres et al. JAMA Oncol. .

Erratum in

Abstract

Importance: MET inhibitors have recently demonstrated clinical activity in patients with MET exon 14 (METex14)-skipping non-small cell lung cancer (NSCLC); however, data with longer follow-up and in larger populations are needed to further optimize therapeutic approaches.

Objective: To assess the long-term efficacy and safety of tepotinib, a potent and highly selective MET inhibitor, in patients with METex14-skipping NSCLC in the VISION study.

Design, setting, and participants: The VISION phase 2 nonrandomized clinical trial was a multicohort, open-label, multicenter study that enrolled patients with METex14-skipping advanced/metastatic NSCLC (cohorts A and C) from September 2016 to May 2021. Cohort C (>18 months' follow-up) was an independent cohort, designed to confirm findings from cohort A (>35 months' follow-up). Data cutoff was November 20, 2022.

Intervention: Patients received tepotinib, 500 mg (450 mg active moiety), once daily.

Main outcomes and measures: The primary end point was objective response by independent review committee (RECIST v1.1). Secondary end points included duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety.

Results: Cohorts A and C included 313 patients (50.8% female, 33.9% Asian; median [range] age, 72 [41-94] years). The objective response rate (ORR) was 51.4% (95% CI, 45.8%-57.1%) with a median (m)DOR of 18.0 (95% CI, 12.4-46.4) months. In cohort C (n = 161), an ORR of 55.9% (95% CI, 47.9%-63.7%) with an mDOR of 20.8 (95% CI, 12.6-not estimable [NE]) months was reported across treatment lines, comparable to cohort A (n = 152). In treatment-naive patients (cohorts A and C; n = 164), ORR was 57.3% (95% CI, 49.4%-65.0%) and mDOR was 46.4 (95% CI, 13.8-NE) months. In previously treated patients (n = 149), ORR was 45.0% (95% CI, 36.8%-53.3%) and mDOR was 12.6 (95% CI, 9.5-18.5) months. Peripheral edema, the most common treatment-related adverse event, occurred in 210 patients (67.1%) (35 [11.2%] experienced grade ≥3 events).

Conclusions and relevance: The findings from cohort C in this nonrandomized clinical trial supported the results from original cohort A. Overall, the long-term outcomes of VISION demonstrated robust and durable clinical activity following treatment with tepotinib, particularly in the treatment-naive setting, in the largest known clinical trial of patients with METex14-skipping NSCLC, supporting the global approvals of tepotinib and enabling clinicians to implement this therapeutic approach for such patients.

Trial registration: ClinicalTrials.gov Identifier: NCT02864992.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Mazieres reported personal fees/advisory board membership from Roche and Bristol Myers Squibb, and AstraZeneca, advisory board membership and research funding (institution), personal fees/advisory board membership from Pfizer, Novartis, Amgen, Takeda, Daiichi Sankyo, the healthcare business of Merck KGaA, Darmstadt, Germany, grants/funding (institution) from Roche/Genentech, Bristol Myers Squibb, and AstraZeneca outside the submitted work. Dr Paik reported advisory board funds, institutional research funding, and/or personal fees from EMD Serono, Takeda DSMC, Janssen, Xencor, Boehringer Ingelheim, CrownBio, Mirati, Calithera, and Novartis outside the submitted work. Dr Garassino reported personal fees from the healthcare business of Merck KGaA, Darmstadt, Germany, during the conduct of the study; grants and personal fees from AstraZeneca, personal fees from the healthcare business of Merck KGaA, Darmstadt, Germany, Bayer, BMS, AbbVie, Takeda, Janssen, Roche, Sanofi, Boheringer Ingelheim, Daiichi Sankyo, Eli Lilly, Novartis, and Blueprint outside the submitted work. Dr Le reported personal/consulting fees from EMD Serono during the conduct of the study; personal or consulting fees from AstraZeneca, Spectrum Pharmaceutics, Novartis, Eli Lilly, Boehringer Ingelheim, Janssen, Blueprint Medicines, Bayer, Albion, grants from ArriVent, Eli Lilly, Boehringer Ingelheim, Regeneron, and personal fees from AbbVie outside the submitted work. Dr Sakai reported personal fees from the healthcare business of Merck KGaA, Darmstadt, Germany, during the conduct of the study; personal fees from Bristol Myers Squibb and Chugai Pharma outside the submitted work. Dr Veillon reported research funding from the healthcare business of Merck KGaA, Darmstadt, Germany, during the conduct of the study; personal consulting fees from Janssen, personal speaker fees from BMS, Takeda, personal speaker bureau fees from Amgen, Sanofi, Roche, AstraZeneca, and travel fees from Pfizer Travel and Janssen outside the submitted work. Dr Smit reported institutional fees for advisory or consultancy services from Lilly, AstraZeneca, Boehringer Ingelheim, Roche/Genentech, Bristol Myers Squibb, Merck & Co Oncology, Takeda, Bayer, Regeneron, Novartis, Daiichi Sankyo, Seattle Genetics, the healthcare business of Merck KGaA, Darmstadt, Germany; and receives research funding (to institution) from Boehringer Ingelheim, Bayer, Roche/Genentech, AstraZeneca, and Bristol Myers Squibb. Dr Cortot reported the healthcare business of Merck KGaA, Darmstadt, Germany, clinical trial investigator fees during the conduct of the study; grants from the healthcare business of Merck KGaA, Darmstadt, Germany, personal fees from Novartis, Roche, Takeda, Amgen, nonfinancial support from Novartis and Amgen, personal fees from Pfizer, nonfinancial support from Pfizer, personal fees from Exeliom, InhaTarget, AbbVie, and grants from AbbVie outside the submitted work. Dr Raskin reported travel expenses from Roche, personal fees from Pfizer, Lilly, Boehringer Ingelheim, BMS, and the healthcare business of Merck KGaA, Darmstadt, Germany, outside the submitted work. Dr Viteri reported personal fees from the healthcare business of Merck KGaA, Darmstadt, Germany, AbbVie, BMS, AstraZeneca, Merck & Co, Roche, nonfinancial support from OSE Immunotherapeutics, personal fees from Janssen and Puma Biotechnology outside the submitted work. Dr Wu reported grants from AstraZeneca; BMS, Pfizer (grant to the institute), personal fees from AstraZeneca, Boehringer Ingelheim, BMS, Eli Lilly, Hengrui, Merck & Co, Pfizer, Sanofi, and speaker fees from Roche outside the submitted work. Dr Yang reported institutional fees for advisory or consultancy services from Amgen, grants from AstraZeneca to conduct investigator-initiated study, institutional fees for advisory or consultancy services from AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Eli Lilly, the healthcare business of Merck KGaA, Darmstadt, Germany, Merck & Co, Novartis, personal fees from Novartis Committee for data safety, and institutional fees for advisory or consultancy services from Pfizer, Roche/Genentech, Takeda, Yuhan Pharmaceuticals, Janssen, Puma Technology, Gilead, and GSK outside the submitted work. Dr Ahn reported personal fees from the healthcare business of Merck KGaA, Darmstadt, Germany, during the conduct of the study; personal fees from AstraZeneca, the healthcare business of Merck KGaA, Darmstadt, Germany, Merck & Co, Yuhan, Takeda, Roche, Alpha pharmaceuticals, and Amgen outside the submitted work. Dr O’Brate reported employment from the healthcare business of Merck KGaA, Darmstadt, Germany, during the conduct of the study. Dr Otto reported personal fees from Merck KGaA, Darmstadt, Germany, employment at the healthcare business of Merck KGaA, Darmstadt, Germany, during the conduct of the study. Dr Johne reported employment and stock holdings from the healthcare business of Merck KGaA, Darmstadt, Germany, during the conduct of the study. Dr Felip reported grants from the healthcare business of Merck KGaA, Darmstadt, Germany (research funding to institution), and Fundación Merck Salud, a private nonprofit institution founded by the healthcare business of Merck KGaA, Darmstadt, Germany (research funding to institution) during the conduct of the study; consulting fees from Amgen, consulting fees, speaker fees from Amgen, AstraZeneca, Bristol Myers Squibb, Eli Lilly, F Hoffmann-La Roche, Janssen, Medical Trends, Medscape, Merck & Co, PeerVoice, Pfizer, Sanofi, Takeda, Touch Oncology, independent board membership at Grifols, consulting fees from AstraZeneca, Bayer, Bristol Myers Squibb, Daiichi Sankyo, Eli Lilly, F Hoffmann-La Roche, GSK, Janssen, the healthcare business of Merck KGaA, Darmstadt, Germany, Merck & Co, Novartis, Peptomyc, Pfizer, Sanofi, Takeda, and BerbenBio, speaker fees from Amgen, AstraZeneca, Bristol Myers Squibb, Eli Lilly, other from F Hoffmann La Roche, Janssen, Medical Trends, Medscape, the healthcare business of Merck KGaA, Darmstadt, Germany, Merck & CoPeerVoice, Pfizer, Sanofi, Takeda, and Touch Oncology outside the submitted work. Dr Thomas reported personal fees from AstraZeneca, Beigene, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, Chugai, Daiichi Sankyo, GSK, Janssen Oncology, Lilly, the healthcare business of Merck KGaA, Darmstadt, Germany, Merck & Co, Novartis, Pfizer, Roche, Sanofi, and Takeda outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Outcomes Following Tepotinib Treatment in Cohorts A and C
A, Duration of response.a B, Progression-free survival. C, Overall survival. NE indicates not estimable. aOnly patients with a response were included in Kaplan-Meier analyses.
Figure 2.
Figure 2.. Change in Sum of Longest Diameters Between Baseline and Best Postbaseline Assessment by IRC in Cohorts A and C
A, Treatment-naive patients. B, Previously treated patients. Four treatment-naive and 4 previously treated patients are not shown due to baseline/on-treatment measurement not being available. IRC indicates independent review committee; L+, positive detection of METex14 skipping in liquid biopsy sample; T+, positive detection of METex14 skipping in tissue biopsy sample.
See this image and copyright information in PMC

Comment in

References

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