Abstract 25P
Background
Tepotinib is an oral, once daily (QD), highly selective, potent MET inhibitor, that has shown durable activity in METex14 skipping advanced NSCLC. Here, we report outcomes in Asian patients (pts) from VISION; these data are relevant to clinical practice as tepotinib is approved in several Asian countries; Japan, Taiwan, South Korea, Singapore, and is available in Hainan, China.
Methods
Pts with advanced METex14 skipping NSCLC, detected by liquid (L+) and/or tissue (T+) biopsy, received tepotinib 500 mg (450 mg active moiety) QD. Primary endpoint was objective response by IRC; secondary endpoints included disease control (DCR), duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety.
Results
VISION enrolled 106 Asian pts (38 in Japan, 20 in South Korea, 12 in Taiwan, 30 in China, 6 outside Asia). At data cut-off (Feb 1, 2021), 79 pts had ≥3 months’ follow-up and were assessed for efficacy (38% were female, 42% had smoking history, 34% were treatment-naïve [1L], 82% had adenocarcinoma, 72% were T+). Objective response rate (ORR) was 54.4% (95% CI: 42.8, 65.7), median (m) DOR was 18.5 months (8.3, not estimable [ne]), mPFS was 12.1 months (6.9, ne), and mOS was 20.4 months (19.1, ne). Meaningful activity was observed across therapy lines (Table). In 1L T+ pts (n=20), ORR was 70.0% (45.7, 88.1) with 83% 12-m DOR rate, 74% 12-m PFS rate, 67% 24-m OS rate (medians ne). In +2L T+ pts (n=37), ORR was 51.4% (34.4, 68.1), mDOR was 8.3 months (4.3, ne), mPFS was 11.1 months (5.6, ne), and mOS was 26.8 months (14.3, ne). At data cut-off, 88 pts received tepotinib and were analyzed for safety. Most common adverse events (AEs) were peripheral edema, creatinine increase, and diarrhea. 29.5% of pts had Grade ≥3 treatment-related (TR) AEs. TRAEs led to dose reduction in 29.5%, temporary interruption in 43.2%, permanent discontinuation in 14.8% of pts. Table: 25P
Tepotinib efficacy (IRC) in Asian patients
| Endpoint | Treatment-naïve n=27 | Previously treated n=52 | |
| ORR, % (95% CI) | 66.7 (46.0, 83.5) | 48.1 (34.0, 62.4) | |
| DCR, % (95% CI) | 77.8 (57.7, 91.4) | 76.9 (63.2, 87.5) | |
| DOR | Median, months (95% CI) | ne (6.9, ne) | 9.7 (5.6, ne) |
| 12-month rate, % (95% CI) | 79 (38, 94) | 29 (5, 60) | |
| PFS | Median, months (95% CI) | ne (8.3, ne) | 11.0 (5.6, 19.9) |
| 12-month rate, % (95% CI) | 66 (40, 83) | 44 (26, 61) | |
| OS | Median, months (95% CI) | ne (16.3, ne) | 20.4 (14.3, ne) |
| 12-month rate, % | 84 (63, 94) | 78 (63, 88) |
IRC, independent review committee; ne, not estimable.
Conclusions
In VISION, tepotinib showed robust and durable clinical activity, with a tolerable safety profile, in Asian pts with METex14 skipping NSCLC.
Clinical trial identification
NCT02864992 (VISION).
Editorial acknowledgement
Medical writing assistance (funded by Merck Healthcare KGaA, Darmstadt, Germany) was provided by 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
J.C. Yang: Other, Institutional, Advisory Role, Advisory or consultancy services: Amgen, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, MSD, Novartis, Roche/Genentech, Takeda Oncology, Yuhan Pharmaceuticals, Ono Pharmaceuticals and Pfizer; Other, Institutional, Funding, Research funding to institution: Eli Lilly, JNJ, Puma Technology, Gilead, GSK, Amgen, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, MSD, Novartis, Roche/Genentech, Takeda Oncology and Yuhan Pharmaceuticals; Financial Interests, Institutional, Advisory Role, Institutional fee for advisory or consultancy services and grant: AstraZeneca. H. Sakai: Financial Interests, Institutional, Speaker’s Bureau, Speakers’ bureau fees: Bristol Myers Squibb, Ono Pharmaceutical, MSD K.K., AstraZeneca, Chugui Pharma, Taiho Pharmaceutical, Boehringer Ingelheim and Merck Healthcare KGaA, Darmstadt, Germany. M. Morise: Financial Interests, Institutional, Speaker’s Bureau, Speakers’ bureau fees: Chugai, MSD, ONO and AstraZeneca. T. Kato: Financial Interests, Institutional, Research Grant, Grants during conduct of the study: Merck Biopharma, an affiliate of Merck KGaA; Other, Institutional, Research Grant, Grants outside the submitted work: Regeneron; Other, Personal and Institutional, Research Grant, Grants and personal fees: AbbVie, Amgen, AstraZeneca, Bristol Myers Squibb, Chugai, Eli Lilly, Merck Biopharma, an affiliate of Merck KGaA, MSD, Novartis, Ono, Pfizer, Taiho and Boehringer Ingelheim; Other, Personal, Other, Personal fees: Daiichi Sankyo, Nippon Kayaku and Takeda. J. Han: Financial Interests, Institutional, Funding, Research funding: Hoffmann-La Roche Ltd, ONO, Pfizer and Takeda; Other, Institutional, Advisory Role, Consulting/advisory role: AstraZeneca, Bristol Myers Squibb, Eli Lilly, MSD, Novartis, Pfizer, Takeda, Medpacto, Abion and ONO; Other, Institutional, Other, Honororia: AstraZeneca, Bristol Myers Squibb, F. Hoffmann-La Roche Ltd, Merck Sharpe & Dohme and Takeda. J. Huang: Financial Interests, Institutional, Full or part-time Employment, Employee of Merck Healthcare KGaA, Darmstadt, Germany: Merck Healthcare KGaA. K. Berghoff: Financial Interests, Institutional, Full or part-time Employment, Employee of Merck Healthcare KGaA, Darmstadt, Germany.: Merck Healthcare KGaA. R. Bruns: Financial Interests, Institutional, Full or part-time Employment, Employee of Merck Healthcare KGaA, Darmstadt, Germany: Merck Healthcare KGaA; Financial Interests, Personal, Stocks/Shares, Mr Bruns holds stock in Merck Healthcare KGaA, Darmstadt, Germany: Merck Healthcare KGaA. G. Otto: Financial Interests, Institutional, Full or part-time Employment, Employee of Merck Healthcare KGaA, Darmstadt, Germany.: Merck Healthcare KGaA. X. Le: Financial Interests, Institutional, Advisory Board, Consulting or advisory role: AstraZeneca, Eli Lilly and EMD Serono, an affiliate of Merck KGaA; Financial Interests, Institutional, Funding, Research funding: Eli Lilly and Boehringer Ingelheim. P. Paik: Other, Institutional, Advisory Role, Advisory role: AstraZeneca, Calithera, Lilly, Takeda, EMD Serono, an affiliate of Merck KGaA, Xencor, Bicara, Boehringer Ingelheim, Xencor and CrownBio; Financial Interests, Institutional, Other, Research institution has received research expenses: Celgene, EMD Serono, an affiliate Merck KGaA, Boehringer Ingelheim and Bicara. All other authors have declared no conflicts of interest.