81P - Tepotinib in patients (pts) with METexon 14 (METex14) skipping non-small cell lung cancer (NSCLC) from the VISION study: ≥3-year follow-up outcomes

Background

Tepotinib, a highly selective MET inhibitor has demonstrated robust and durable efficacy and safety in pts with METex14 skipping NSCLC in Cohorts A+C (data cut-off: Nov 20, 2022; follow-up: Cohort A >35 months, Cohort C >18 months) and in pts with high-level MET amplification (METamp) NSCLC in Cohort B of the Phase II VISION study (NCT02864992). We report long-term efficacy and safety outcomes from VISION in pts with ≥3-years follow-up (data cut-off: May 20, 2024).

Methods

Pts with advanced NSCLC and METex14 skipping or METamp received tepotinib 500 mg (450 mg active moiety) once daily. Primary endpoint was objective response by independent review using RECIST v1.1. Secondary endpoints included duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety.

Results

Of 313 pts enrolled in Cohorts A+C (male: 49.2%; median age [range]: 72 years [41–94]; ECOG PS 1: 73.8%; smoking history: 47.6%), the median duration of treatment was 7.5 months (range: 0.03–83.12) and treatment was ongoing in 18 pts (first-line [1L]: 12/164; second-or-later line [2L+]: 6/149). Overall, objective response rate (ORR) was 51.8% (95% CI: 46.1, 57.4) and median (m) DOR was 18.0 months (12.6, 31.8). In 1L pts, ORR was 57.9% (50.0, 65.6) and mDOR was 31.7 months (13.8, 46.4), while in 2L+ pts, ORR was 45.0% (36.8, 53.3) and mDOR was 12.6 months (9.5, 18.5) (Table). No new safety concerns were observed. Grade ≥3 treatment-related adverse events (TRAEs) occurred in 36.1% of pts, while 15.7% of pts discontinued treatment due to TRAEs. Long-term outcomes from Cohort B will also be presented.

1L, first-line; 2L+, second-or-later line; CI, confidence interval; DOR, duration of response; m, median; ORR, objective response rate; OS, overall survival; PFS, progression-free survival.

Conclusions

In VISION pts with ≥3-years follow-up, tepotinib continued to demonstrate robust and durable activity across treatment lines. Importantly, outcomes in pts with METex14 skipping were consistent with previous results, reinforcing tepotinib as a meaningful treatment option in this setting.

Clinical trial identification

NCT02864992.

Editorial acknowledgement

Medical writing assistance (funded by Merck) was provided by Bhartendu K Srivastava, PhD of Syneos Health, London, UK.

Legal entity responsible for the study

Merck Healthcare KGaA, Darmstadt, Germany.

Funding

Merck (CrossRef Funder ID: 10.13039/100009945).

Disclosure

J. Mazieres: Financial Interests, Personal, Advisory Board: Roche, BMS, MSD, AstraZeneca, Pfizer, Novartis, Merck, Amgen, Takeda, Daiichi Sankyo; Financial Interests, Institutional, Other, Research funding: Roche/Genentech, AstraZeneca, Bristol Myers Squibb. R. Veillon: Financial Interests, Personal, Other, Research funding: Merck; Financial Interests, Personal, Other, Consulting fees: Janssen; Financial Interests, Personal, Other, Speaker fees: BMS, Takeda; Financial Interests, Personal, Speaker’s Bureau: Amgen, Sanofi, Roche, AstraZeneca; Financial Interests, Personal, Other, Travel fees: Pfizer, Janssen. A.B. Cortot: Financial Interests, Personal, Other, Research funding: Novartis, Merck; Financial Interests, Personal, Other, Honoraria: AstraZeneca, BMS, Novartis, MSD, Pfizer, Roche, Takeda; Financial Interests, Personal, Advisory Role: AstraZeneca, BMS, Novartis, Pfizer, Roche, Takeda; Financial Interests, Personal, Other, Travel expenses: AstraZeneca, MSD, Novartis, Pfizer, Roche, Takeda. R. Ferrara: Financial Interests, Personal, Advisory Board: MSD, BeiGene. E. Felip: Financial Interests, Personal, Advisory Role: Pfizer, Roche, Boehringer Ingelheim, AstraZeneca, BMS, Guardant Health, Novartis, Takeda, AbbVie, Blue Print Medicines, Lilly, Merck, MSD, Janssen, Samsung; Financial Interests, Personal, Other, Speaker’s bureau/expert testimony: Pfizer, Roche, AstraZeneca, BMS, Novartis, Takeda, Lilly, MSD, Medscape, prIME Oncology, Touchtime; Financial Interests, Personal, Research Grant, Grant for Oncology Innovation (GOI): Fundación Merck Salud, a private non-profit institution founded by Merck, S.L.U., Madrid, Spain, an affiliate of Merck KGaA; Financial Interests, Personal, Officer, Independent member: Grifols. M.C. Garassino: Financial Interests, Personal, Other, Honoraria: MSD Oncology, AstraZeneca/MedImmune, GSK, Takeda, Roche, BMS; Financial Interests, Personal, Advisory Role: BMS, MSD, AstraZeneca, Novartis, Takeda, Roche, Tiziana Life Sciences, Sanofi-Aventis, Celgene, Daiichi Sankyo, Inivata, Incyte, Pfizer, Seattle Genetics, Eli Lilly, GSK, Bayer Healthcare Pharmaceuticals, Blueprint Medicines, Janssen, Regeneron; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Takeda, MSD Oncology, Celgene, Incyte, Roche, BMS, Otsuka, Eli Lilly; Financial Interests, Institutional, Other, Research funding: BMS, MSD, Roche/Genentech, AstraZeneca/MedImmune, AstraZeneca, Pfizer, GSK, Novartis, Merck, Incyte, Takeda, Spectrum Pharmaceuticals, Blueprint Medicines, Eli Lilly, Ipsen, Janssen, Exelixis, MedImmune, Sanofi, Pfizer, Amgen; Financial Interests, Personal, Other, Travel and accommodation expenses: Pfizer; Financial Interests, Personal, Invited Speaker, Travel and accommodation expenses: Roche, AstraZeneca. X. Le: Financial Interests, Personal, Advisory Role: AstraZeneca, Eli Lilly, EMD Serono Research & Development Institute, Inc., Billerica, MA, USA, an affiliate of Merck KGaA, Novartis, Daiichi Sankyo, Hengrui Therapeutics; Financial Interests, Personal, Other, Research funding: Eli Lilly, Boehringer Ingelheim. M. Thomas: Financial Interests, Personal, Other, Honoraria – Scientific Meetings (self): AbbVie, BMS, MSD, AstraZeneca, Novartis, Roche, Takeda, Lilly, Chugai, Celgene, Boehringer Ingelheim, Pfizer, Janssen, GSK, Merck, Sanofi, Amgen; Financial Interests, Personal, Other, Travelling support (self): AbbVie, BMS, MSD, AstraZeneca, Novartis, Roche, Takeda, Lilly, Chugai Pharma, Celgene, Boehringer Ingelheim, Pfizer; Financial Interests, Personal, Advisory Board: AbbVie, BMS, MSD, AstraZeneca, Novartis, Roche, Takeda, Lilly, Chugai Pharma, Celgene, Boehringer Ingelheim, Pfizer, Janssen, Daiichi Sankyo, GSK, Merck, Sanofi, Amgen; Financial Interests, Institutional, Other, Research funding: BMS, AstraZeneca, Roche, Takeda. H. Sakai: Financial Interests, Personal, Speaker’s Bureau: BMS, Ono Pharmaceutical, MSD K.K., AstraZeneca, Chugai Pharma, Taiho Pharmaceutical, Boehringer Ingelheim. E.F. Smit: Financial Interests, Institutional, Advisory Role: Lilly, AstraZeneca, Boehringer Ingelheim, Roche/Genentech, BMS, MSD Oncology, Takeda, Bayer, Regeneron, Novartis, Daiichi Sankyo, Seattle Genetics; Financial Interests, Institutional, Other, Research funding: Boehringer Ingelheim, Bayer, Roche/Genentech, AstraZeneca, BMS. J. Raskin: Financial Interests, Personal, Advisory Role: Merck, Lilly, AstraZeneca, Pfizer, BMS. S. Viteri: Financial Interests, Personal, Advisory Role: AbbVie, BMS, Roche, Takeda, AstraZeneca, MSD; Financial Interests, Personal, Speaker’s Bureau: BMS, MSD, Roche, AstraZeneca; Financial Interests, Personal, Other, Travel expenses: Roche, OSE Pharma, BMS, MSD, Merck, Puma Biotechnology, Janssen Cilag. J.C. Yang: Financial Interests, Personal, Advisory Role: Amgen, Bayer, Boehringer Ingelheim, BMS, Daiichi Sankyo, MSD, Novartis, Roche/Genentech, Takeda Oncology, Yuhan Pharmaceuticals, Ono Pharmaceuticals, Pfizer. M. Ahn: Financial Interests, Personal, Advisory Role: AstraZeneca, Lilly, Amgen, Merck, MSD, Takeda, ONO, Pfizer, Yuhan, Alpha-pharmaceuticals, Daiichi Sankyo, Roche. Y. Wu: Financial Interests, Personal and Institutional, Other, Institute grants and personal fees: AstraZeneca, Roche, Boehringer Ingelheim; Financial Interests, Personal, Invited Speaker, Personal fees: BMS, MSD, Eli Lilly, Pfizer. V. Ghori: Financial Interests, Personal, Full or part-time Employment: Ares Trading SA, Eysins, Switzerland, an affiliate of Merck KGaA. R. Bruns: Financial Interests, Personal, Full or part-time Employment: Merck; Financial Interests, Personal, Stocks/Shares: Merck. A. Johne: Financial Interests, Personal, Full or part-time Employment: Merck; Financial Interests, Personal, Stocks/Shares: Merck. P.K. Paik: Financial Interests, Institutional, Other, Grants or contracts (institutional research): EMD Serono Research & Development Institute, Inc., Billerica, MA, USA, an affiliate of Merck KGaA, Bicara; Financial Interests, Personal, Other, Consulting fees: Novartis, AstraZeneca, Janssen, Bicara; Financial Interests, Personal, Other, Honoraria: IDEOlogy, Touch IME, Excerpta Medica, ACE Oncology, Physicians Education Resource, Axis Medical Education, PeerVoice, Aptitude Health, MJH. All other authors have declared no conflicts of interest.