383MO - Tepotinib in Asian patients (pts) with advanced NSCLC with MET exon 14 (METex14) skipping

Background

Tepotinib, an oral, once daily (QD), highly selective, potent MET inhibitor that has shown durable activity in pts with METex14 skipping advanced NSCLC, is approved in Japan. The phase II VISION study showed an overall objective response rate (ORR) of 44.5–47.4% by independent review (IRC), and 54.7–58.3% by investigator assessment (INV); onset of response was mostly observed within 6 weeks. Here, we report outcomes in Asian pts.

Methods

Pts with advanced EGFR/ALK wild-type and METex14 skipping NSCLC, detected by liquid or tissue biopsy, received oral tepotinib 500 mg QD until disease progression, intolerable toxicity, or withdrawal of consent. The primary endpoint was objective response (OR) (confirmed by two scans ≥4 weeks apart) by IRC; secondary endpoints were OR by INV, duration of response (DOR), progression-free survival (PFS), and safety. Pts evaluable for ORR had ≥2 post-baseline assessments or discontinuation for any reason.

Results

At data cut-off (Jan 1, 2020), 38 pts evaluable for efficacy were Asian with a median age of 70 years (52–85), 32% female, 39% non-smokers, and 32% treatment naïve. Asian pts were enrolled from Japan (50%), Korea (26%), Taiwan (13%), Spain (3%), and the US (8%). Efficacy of tepotinib in Asian pts was similar to the overall population; ORR (95% CI) was 47.4% (31.0, 64.2) by IRC (median DOR [mDOR] was not reached) and 60.5% (43.4, 76.0) by INV (mDOR was 10.9 months [9.7, ne]). Disease control rate (confirmed complete or partial response, or stable disease lasting ≥12 weeks) was 68.4% (51.3, 82.5) by IRC and 81.6% (65.7, 92.3) by INV. Although still immature, median PFS (95% CI) was 11.0 months (4.9, ne). Overall, 50 Asian pts received at least one dose of tepotinib. The most common adverse events (any cause) were peripheral edema, increased blood creatinine, and diarrhea. Grade ≥3 treatment-related adverse events (TRAEs) were observed in 26% of pts. TRAEs led to dose reductions in 28%, temporary discontinuation in 36%, and permanent discontinuation in 10% of pts.

Conclusions

Tepotinib showed robust, durable clinical activity in Asian pts with METex14 skipping NSCLC. Adverse events were mostly mild and manageable, with few discontinuations. The VISION study will enroll pts at 55 sites in Asia.

Clinical trial identification

NCT02864992; 13 September, 2016.

Editorial acknowledgement

Medical writing assistance (funded by Merck KGaA, Darmstadt, Germany) was provided by Syneos Health, London, UK.

Legal entity responsible for the study

Merck KGaA, Darmstadt, Germany.

Funding

Merck KGaA, Darmstadt, Germany.

Disclosure

J.C-H. Yang: Advisory/Consultancy, personal fees: Boehringer Ingelheim; Advisory/Consultancy, personal fees: Eli Lilly; Advisory/Consultancy, personal fees: Bayer; Advisory/Consultancy, personal fees: Roche/Genentech; Advisory/Consultancy, personal fees: Chugai Pharmaceutical; Advisory/Consultancy, personal fees: MSD; Advisory/Consultancy, personal fees: Pfizer; Advisory/Consultancy, personal fees: Novartis; Advisory/Consultancy, personal fees: BMS; Advisory/Consultancy, personal fees: Ono Pharmaceuticals; Advisory/Consultancy, personal fees: AstraZeneca; Advisory/Consultancy, personal fees: ACT Genomics; Advisory/Consultancy, personal fees: Merck Serono; Advisory/Consultancy, personal fees: Celgene; Advisory/Consultancy, personal fees: Yuhan Pharmaceuticals; Advisory/Consultancy, personal fees: Daiichi Sankyo; Advisory/Consultancy, personal fees: Hansoh Pharmaceuticals; Advisory/Consultancy, personal fees: Takeda Pharmaceuticals; Advisory/Consultancy, personal fees: Blueprint Medicines; Advisory/Consultancy, personal fees: Amgen. X. Le: Advisory/Consultancy: AstraZeneca; Advisory/Consultancy, Research grant/Funding (self): Eli Lilly; Advisory/Consultancy: EMD Serono; Research grant/Funding (self): Boehringer Ingelheim. B.C. Cho: Advisory/Consultancy, Research grant/Funding (self): Novartis; Research grant/Funding (self): Bayer; Advisory/Consultancy, Research grant/Funding (self): AstraZeneca; Research grant/Funding (self): MOGAM Institute; Research grant/Funding (self): Dong-A ST; Research grant/Funding (self), Licensing/Royalties: Champions Oncology; Advisory/Consultancy, Research grant/Funding (self): Janssen; Advisory/Consultancy, Research grant/Funding (self): Yuhan; Advisory/Consultancy, Research grant/Funding (self): Ono; Research grant/Funding (self): Dizal Pharma; Advisory/Consultancy, Research grant/Funding (self): MSD; Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy: Roche; Advisory/Consultancy: BMS; Advisory/Consultancy: Eli Lilly; Advisory/Consultancy: Takeda; Advisory/Consultancy: Pfizer; Shareholder/Stockholder/Stock options: TheraCanVac Inc; Shareholder/Stockholder/Stock options: Gencurix Inc; Shareholder/Stockholder/Stock options: Bridgebio Therapeutics. M. Morise: Speaker Bureau/Expert testimony: Chugai; Speaker Bureau/Expert testimony: MSD; Speaker Bureau/Expert testimony: ONO; Speaker Bureau/Expert testimony: AstraZeneca. J-H. Kang: Research grant/Funding (self): CKD; Advisory/Consultancy, Research grant/Funding (self): AstraZeneca; Advisory/Consultancy, Research grant/Funding (self): Yuhan; Research grant/Funding (self): Ono; Advisory/Consultancy, Research grant/Funding (self): Boehringer Ingelheim; Research grant/Funding (self): Daichii Sankyo; Advisory/Consultancy: MSD; Advisory/Consultancy: Roche; Advisory/Consultancy: BMS; Advisory/Consultancy: Eli Lilly; Advisory/Consultancy: Genexin. T. Kato: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Spouse/Financial dependant, Immediate family member employment: Lilly; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy: MSD; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Chugai Pharma; Honoraria (self), Advisory/Consultancy: Nitto Denko; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): AbbVie; Advisory/Consultancy, Research grant/Funding (institution): Merck Serono; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Honoraria (self): Roche; Honoraria (self): Boehringer Ingelheim; Honoraria (self), Research grant/Funding (institution): Ono Pharmaceutical; Honoraria (self), Research grant/Funding (institution): Taiho Pharmaceutical; Honoraria (self), Research grant/Funding (self): BMS; Honoraria (self), Research grant/Funding (institution): Merck Sharp & Dohme; Honoraria (self), Research grant/Funding (self): Novartis; Honoraria (self): Sumitomo Dainippon Pharma; Honoraria (self): Takeda; Honoraria (self): Merck KGaA; Honoraria (self): Daiichi Sankyo; Honoraria (self): Shionogi; Honoraria (self): Nippon Kayaku; Research grant/Funding (self): Kyorin; Research grant/Funding (self): Regenoron; Research grant/Funding (self), Research grant/Funding (institution): Kyowa Hakko Kirin. H. Sakai: Speaker Bureau/Expert testimony: BMS; Speaker Bureau/Expert testimony: Ono Pharmaceutical; Speaker Bureau/Expert testimony: MSD K.K.; Speaker Bureau/Expert testimony: AstraZeneca; Speaker Bureau/Expert testimony: Chugui Pharma; Speaker Bureau/Expert testimony: Taiho Pharmaceutical; Speaker Bureau/Expert testimony: Boehringer Ingelheim; Speaker Bureau/Expert testimony: Merck KGaA. K. Park: Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy: Clovis; Advisory/Consultancy: Eli Lilly; Advisory/Consultancy: Hanmi; Advisory/Consultancy: Novartis; Advisory/Consultancy: Ono; Advisory/Consultancy: Roche. Y-L. Wu: Advisory/Consultancy, Research grant/Funding (institution), personal fees: AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution), personal fees: Roche; Advisory/Consultancy, Research grant/Funding (institution), personal fees: Boehringer Ingelheim; Speaker Bureau/Expert testimony, personal fees (speaker): BMS; Speaker Bureau/Expert testimony, personal fees (speaker): MSD; Speaker Bureau/Expert testimony, personal fees (speaker): Eli Lilly; Speaker Bureau/Expert testimony, personal fees (speaker): Pfizer. K. Schumacher, R. Bruns, J. Straub: Full/Part-time employment: Merck KGaA, Darmstadt, Germany. P. Paik: Advisory/Consultancy: AbbVie; Advisory/Consultancy: BMS; Advisory/Consultancy: Calithera; Advisory/Consultancy, Research grant/Funding (institution): Celgene; Advisory/Consultancy: Lilly; Advisory/Consultancy: Takeda; Research grant/Funding (self), Research grant/Funding (institution): EMD Serono. All other authors have declared no conflicts of interest.