Abstract 985P
Background
Tepotinib is a MET inhibitor approved by the European Commission for patients (pts) with advanced METex14 skipping NSCLC, with prior immunotherapy (IO) and/or platinum-based chemotherapy (CT). Here, we report the first analysis of tepotinib according to prior therapies from all pts with METex14 skipping NSCLC in VISION (data cut-off: Feb 20, 2022).
Methods
Pts with advanced/metastatic METex14 skipping NSCLC, detected by tissue (TBx) and/or liquid biopsy, received 500 mg (450 mg active moiety) tepotinib QD. Primary endpoint: objective response by IRC (RECIST 1.1). Predefined analyses included first-line (1L), second-line (2L), second-or-later line (≥2L), and pts with METex14 skipping by TBx (T+) – the most widely used detection method.
Results
Of 313 pts enrolled, 149 received tepotinib as ≥2L (median age 70.8 yrs [range, 41–89], 52.3% female, 40.9% had smoking history), and 92 as 2L. Prior treatments include platinum-based CT in 126 pts (84.6%) and IO in 81 pts (54.4%; in 36/92 [39.1%] 2L pts and in 45/57 [78.9%] ≥3L pts); as IO monotherapy in 59 pts (39.6%); as IO-CT in 22 pts (14.8%). Objective response rate (ORR) for 2L pts who received CT alone as 1L was 50.0% (95% CI: 36.1, 63.9) overall and 60.5% (43.4, 76.0) in T+ pts. ORR in 2L pts with prior IO-CT was 62.5% (35.4, 84.8) overall and 63.6% (30.8, 89.1) in T+ pts. Among 164 pts who received tepotinib as 1L (median age 74.0 yrs [range, 47–94], 49.4% female, 53.7% had smoking history), ORR was 56.1% (48.1, 63.8) with mDOR of 46.4 months (13.8, ne). Robust efficacy was also observed in T+ pts. Treatment-related adverse events (TRAEs) occurred in 91.7% of pts (1L: 94.5%, ≥2L: 88.6%, prior IO: 90.1%); 34.2% had Grade ≥3 TRAEs (1L: 40.9%, ≥2L: 26.8%, prior IO: 27.2%) and 14.7% discontinued due to TRAEs (1L: 15.2%, ≥2L: 14.1%, prior IO: 17.3%). Table: 985P
| Tepotinib efficacy | ORR, % (95% CI) | mDOR, months (95% CI) | mPFS, months (95% CI) | mOS, months (95% CI) | |
| 1L | Overall (n=164) | 56.1 (48.1, 63.8) | 46.4 (13.8, ne) | 12.6 (9.6, 17.7) | 19.1 (13.7, 23.7) |
| T+ (n=111) | 56.8 (47.0, 66.1) | 46.4 (13.4, ne) | 15.3 (11.3, ne) | 25.9 (17.5, 36.6) | |
| 2L | Overall (n=92) | 45.7 (35.2, 56.4) | 12.6 (8.3, 20.8) | 10.9 (8.2, 13.8) | 20.0 (15.8, 23.7) |
| T+ (n=65) | 53.8 (41.0, 66.3) | 12.4 (7.0, 20.8) | 13.7 (8.2, 19.4) | 20.9 (17.7, 32.5) | |
| ≥2L | Overall (n=149) | 45.0 (36.8, 53.3) | 12.4 (9.5, 18.5) | 11.0 (8.2, 13.7) | 19.6 (15.2, 22.3) |
| T+ (n=97) | 49.5 (39.2, 59.8) | 10.2 (8.3, 18.0) | 11.5 (8.2, 16.8) | 20.4 (17.0, 26.8) |
Conclusions
In VISION – the largest study of a MET inhibitor in pts with METex14 skipping NSCLC – tepotinib demonstrated robust and durable efficacy irrespective of prior therapies and had a tolerable safety profile.
Clinical trial identification
NCT02864992.
Editorial acknowledgement
Medical writing assistance (funded by Merck Healthcare KGaA, Darmstadt, Germany) was provided by Carys Davies of Syneos Health, London, UK.
Legal entity responsible for the study
Merck Healthcare KGaA, Darmstadt, Germany.
Funding
Merck Healthcare KGaA, Darmstadt, Germany (CrossRef Funder ID: 10.13039/100009945).
Disclosure
E.F. Smit: Financial Interests, Institutional, Advisory Role: Lilly; AstraZeneca; Boehringer Ingelheim; Roche/Genentech; Bristol Myers Squibb; Merck Healthcare KGaA, Darmstadt, Germany; MSD Oncology; Takeda; Bayer; Regeneron; Novartis; Daiichi Sankyo; Seattle Genetics; Financial Interests, Institutional, Research Grant: Boehringer Ingelheim; Bayer; Roche/Genentech; AstraZeneca; Bristol Myers Squibb. M.C. Garassino: Financial Interests, Personal, Other, Honoraria: MSD Oncology; AstraZeneca/MedImmune; GlaxoSmithKline; Takeda; Roche; Bristol Myers Squibb; Financial Interests, Personal, Advisory Role: Bristol Myers Squibb; MSD; AstraZeneca; Novartis; Takeda; Roche; Tiziana Life Sciences; Sanofi-Aventis; Celgene; Daiichi Sankyo; Inivata; Incyte; Pfizer; Seattle Genetics; Eli Lilly; GlaxoSmithKline; Bayer Healthcare Pharmaceuticals; Blueprint Medicines; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca; Takeda; MSD Oncology; Celgene; Incyte; Roche; Bristol Myers Squibb; Otsuka; Eli Lilly; Financial Interests, Institutional, Research Grant: Bristol Myers Squibb; MSD; Roche/Genentech; AstraZeneca/MedImmune; AstraZeneca; Pfizer; GlaxoSmithKline; Novartis; Merck Healthcare KGaA, Darmstadt, Germany; Incyte; Takeda; Spectrum Pharmaceuticals; Blueprint Medicines; Eli Lilly; Ipsen; Janssen; Exelixi; Financial Interests, Personal, Other, Travel and accommodation expenses: Pfizer; Roche; AstraZeneca. E. Felip: Financial Interests, Personal, Advisory Role: Pfizer; Roche; Boehringer Ingelheim; AstraZeneca; Bristol Myers Squibb; Guardant Health; Novartis; Takeda; AbbVie; Blueprint Medicines; Lilly; Merck Healthcare KGaA, Darmstadt, Germany; Merck Sharp & Dohme; Janssen; Samsung; Financial Interests, Personal, Speaker’s Bureau: Pfizer; Roche; AstraZeneca; Bristol Myers Squibb; Novartis; Takeda; Lilly; Merck Sharp & Dohme; Medscape; prIME Oncology; Touchtime; Financial Interests, Personal, Research Grant: Fundación Merck Salud, a private non-profit institution founded by Merck, S.L.U., Madrid, Spain, an affiliate of Merck KGaA; Grant for Oncology Innovation (GOI); Financial Interests, Personal, Member of the Board of Directors: Grifols (Independent Member). H. Sakai: Financial Interests, Personal, Speaker’s Bureau: Bristol Myers Squibb; Ono Pharmaceutical; MSD K.K.; AstraZeneca; Chugui Pharma; Taiho Pharmaceutical; Boehringer Ingelheim. X. Le: Financial Interests, Personal, Advisory Role: AstraZeneca; Eli Lilly; EMD Serono, an affiliate of Merck KGaA; Novartis; Daiichi Sankyo; Hengrui Therapeutics; Financial Interests, Personal, Research Grant: Eli Lilly, Boehringer Ingelheim. R. Veillon: Financial Interests, Personal, Advisory Role: MSD; Pfizer; Novartis; Financial Interests, Personal, Speaker’s Bureau: MSD; Bristol Myers Squibb; Roche; Financial Interests, Personal, Research Grant: Roche; Takeda; AbbVie; Merck Healthcare KGaA, Darmstadt, Germany; Bristol Myers Squibb. J. Mazieres: Financial Interests, Personal, Advisory Board: Roche; Bristol Myers Squibb; MSD; AstraZeneca; Pfizer; Novartis; Merck Healthcare KGaA, Darmstadt, Germany; Amgen; Takeda; Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Roche/Genentech; AstraZeneca; Bristol Myers Squibb. A. Cortot: Financial Interests, Personal, Research Grant: Novartis; Merck Healthcare KGaA, Darmstadt, Germany; Financial Interests, Personal, Other, Honoraria: AstraZeneca; Bristol Myers Squibb; Novartis; MSD; Pfizer; Roche; Takeda; Financial Interests, Personal, Advisory Role, Consulting or advisory role: AstraZeneca; Bristol Myers Squibb; Novartis; Pfizer; Roche; Takeda; Financial Interests, Personal, Other, Travel expenses: AstraZeneca; MSD; Novartis; Pfizer; Roche; Takeda. J. Raskin: Financial Interests, Personal, Advisory Role: Pfizer; Lilly; Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim; Bristol Myers Squibb; Financial Interests, Personal, Other, Travel expenses: Roche. M. Thomas: Financial Interests, Personal, Other, Honoraria for Scientific Meetings (self): AbbVie; Bristol Myers Squibb; MSD; AstraZeneca; Novartis; Roche; Takeda; Lilly; Chugai Pharma; Celgene; Boehringer Ingelheim; Pfizer; Janssen; GSK; Merck Healthcare KGaA, Darmstadt, Germany; Sanofi; Amgen; Financial Interests, Personal, Advisory Board: AbbVie; Bristol Myers Squibb; MSD; AstraZeneca; Novartis; Roche; Takeda; Lilly; Chugai Pharma; Celgene; Boehringer Ingelheim; Pfizer; Janssen; Daiichi Sankyo; GSK; Merck Healthcare KGaA, Darmstadt, Germany; Sanofi; Amgen; Financial Interests, Institutional, Research Grant: Bristol Myers Squibb; AstraZeneca; Roche; Takeda; Financial Interests, Personal, Other, Travelling support: AbbVie; Bristol Myers Squibb; MSD; AstraZeneca; Novartis; Roche; Takeda; Lilly; Chugai Pharma; Celgene; Boehringer Ingelheim; Pfizer. S. Viteri Ramirez: Financial Interests, Personal, Advisory Role: AbbVie; Bristol Myers Squibb; Roche; Takeda; AstraZeneca; MSD; Financial Interests, Personal, Speaker’s Bureau: Bristol Myers Squibb; MSD; Roche; AstraZeneca; Financial Interests, Personal, Other, Travel expenses: Roche; OSE Pharma; Bristol Myers Squibb; Merck Sharpe & Dohme; Merck Healthcare KGaA, Darmstadt, Germany; Puma Biotechnology; Janssen Cilag. K. Berghoff: Financial Interests, Personal, Full or part-time Employment: Merck Healthcare KGaA, Darmstadt, Germany. R. Bruns: Financial Interests, Personal, Full or part-time Employment: Merck Healthcare KGaA, Darmstadt, Germany; Financial Interests, Personal, Stocks/Shares: Merck Healthcare KGaA, Darmstadt, Germany. G.P. Otto: Financial Interests, Personal, Full or part-time Employment: Merck Healthcare KGaA, Darmstadt, Germany; Financial Interests, Personal, Stocks/Shares: Novartis. P.K. Paik: Financial Interests, Personal, Advisory Role: AstraZeneca; Calithera; Lilly; Takeda; EMD Serono, an affiliate of Merck KGaA; Xencor; Bicara; Boehringer Ingelheim; Xencor; CrownBio; Financial Interests, Institutional, Research Grant: EMD Serono, an affiliate Merck KGaA; Boehringer Ingelheim; Bicara.