321MO - Tepotinib in patients with MET exon 14 (METex14) skipping NSCLC: Results from all Asian patients in VISION

Background

Tepotinib, a MET TKI, is approved for METex14 skipping NSCLC in several Asian countries. In VISION (N=313; data cut-off: Feb 20, 2022), tepotinib demonstrated durable clinical activity with an objective response rate (ORR) of 50.8% and a median (m) duration of response (DOR) of 18.0 months. Tepotinib also showed promising intracranial activity in patients (pts) with brain metastases. We report data from all 106 Asian pts with METex14 skipping NSCLC enrolled in VISION.

Methods

Pts with advanced METex14 skipping NSCLC, detected by liquid (L+) and/or tissue biopsy (T+) received tepotinib 500 mg (450 mg active moiety) once daily. Primary endpoint: objective response (RECIST 1.1) by IRC. Secondary endpoints included disease control (DCR), DOR, progression-free survival (PFS), overall survival (OS), and safety (analysis sets: T+, L+, T+ and/or L+).

Results

In 106 Asian pts enrolled in VISION (Japan - 38, South Korea - 20, Taiwan -12, China - 30, outside Asia - 6), median age was 70.5 yrs (range 52–89), 39.6% were female, 43.4% had smoking history, 79.2% had adenocarcinoma, 73.6% had ECOG PS 1, and 47.2% were treatment-naïve. 45.3% were L+ and 78.3% were T+. ORR was 57.5% (95% CI: 47.6, 67.1), DCR was 80.2% (71.3, 87.3), mDOR was 18.5 months (10.4, ne), mPFS was 13.8 months (9.6, 19.9), and mOS was 23.7 months (19.3, ne). In treatment naïve pts (n=50), ORR was 66.0% (51.2, 78.8), and in previously treated pts (n=56), ORR was 50.0% (36.3, 63.7). Meaningful activity was observed irrespective of METex14 skipping detection method (Table). Treatment-related adverse events (TRAEs) occurred in 95.3% of pts; 38.7% had Grade ≥3 TRAEs. TRAEs led to dose reduction in 30.2%, and permanent discontinuation in 13.2% of pts. Most common adverse events were peripheral edema (65.1%), creatinine increase (42.5%), and hypoalbuminemia (40.6%). Table: 321MO

CI, confidence interval; L+, METex14 skipping detected by liquid biopsy; ne, not estimable; T+, METex14 skipping detected by tissue biopsy. *25 patients had METex14 skipping detected by both liquid and tissue biopsy.

Conclusions

Tepotinib demonstrated robust and durable efficacy, with a manageable safety profile, in Asian pts with METex14 skipping NSCLC in VISION.

Clinical trial identification

NCT02864992.

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.

Disclosure

J.C. Yang: Financial Interests, Institutional, Advisory Board: Astrazeneca, Boehringer Ingelheim, Daiichi Sankyo, Amgen, Novartis, Bayer, GSK, Takeda Oncology, Puma Pharmaceuticals, Ono Pharmaceuticals, Merck Serono, MSD, Pfizer, Eli Lilly, Roche/Genentech, Janssen; Financial Interests, Institutional, Invited Speaker: Astrazeneca, Boehringer Ingelheim, Novartis, Astrazeneca, MSD, Ipsen, Takeda Oncology; Financial Interests, Personal, Advisory Board: Yuhan Pharmaceuticals; Financial Interests, Personal, Invited Speaker: Dizal Pharmaceutical, Novartis, Numab, Merck, Daiichi Sankyo, Eli Lilly, Bayer, Janssen; Non-Financial Interests, Personal, Leadership Role, Board of Director: IASLC; Non-Financial Interests, Personal, Member: ASCO. T. Kato: Financial Interests, Personal, Advisory Board, speaker, consultancy: AstraZeneca, Eli Lilly, Merck Biopharma, MSD; Financial Interests, Personal, Advisory Board, speaker: Pfizer; Financial Interests, Personal, Other, consultancy: Daiichi-Sankyo, Takeda, Taiho; Financial Interests, Personal, Other, consultancy, speaker: Chugai; Financial Interests, Personal, Invited Speaker: Ono, Novartis; Financial Interests, Personal, Advisory Board: BeiGene, Glaxo; Financial Interests, Personal, Full or part-time Employment, Family member: Eli Lilly; Financial Interests, Institutional, Invited Speaker: Chugai, MSD, Pfizer, AstraZeneca, Eli Lilly, AbbVie, Regeneron, Novartis, Amgen, Merck Biophama, Haihe Biopharma, Blueprint Medicines, Turning Point. M. Ahn: Financial Interests, Personal, Advisory Board: AstraZeneca, Lilly, Takeda, MSD, Yuhan, Amgen, Alpha Pharmaceutical, Janssen, BMS, Roche, Daichi Sankyo. H. Sakai: Financial Interests, Personal, Speaker’s Bureau: BMS, Ono Pharmaceutical, MSD K K, AstraZeneca, Chugai Pharma, Taiho Pharmaceutical, Boehringer Ingelheim, Merck Healthcare KGaA Darmastadt Germany. M. Morise: Financial Interests, Personal, Speaker’s Bureau: Chugai, MSD, ONO, AstraZeneca. J. Han: Financial Interests, Personal, Funding: Hoffman-La Roche Ltd., ONO, Pfizer, Takeda; Financial Interests, Personal, Advisory Role: AstraZeneca, Bristol Myers Squibb, Eli Lilly, Merck Sharp & Dohme, Novartis, Pfizer, Takeda, Medpacto, Abion, ONO; Financial Interests, Personal, Other, Honoraria: AstraZeneca, Bristol Myers Squibb, F Hoffmann-La Roche Ltd., Merck Sharpe & Dohme, Takeda. J.L. Huang, K. Berghoff, H. Vioix: Financial Interests, Personal, Other, Employee: 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, Other, Employee: Merck Healthcare, KGaA, Darmstadt, Germany; Financial Interests, Personal, Other, Stocks: Novartis. X. Le: Financial Interests, Personal, Advisory Role: AstraZeneca, Eli Lilly, EMD Serono an affiliate of Merck KGaA; Financial Interests, Personal, Research Grant: Eli Lilly, Boehringer Ingelheim. P.K. Paik: Financial Interests, Personal, Advisory Role: Calithera, Takeda, Xencor, CrownBio, Bicara, Mirati, EMD Serono an affiliate of Merck KGaA; Financial Interests, Institutional, Research Grant: Bicara, Boehringer Ingelheim, EMD Serono an affiliate of Merck KGaA. All other authors have declared no conflicts of interest.