MET exon 14 skipping (METex14), reported in 3–4% of NSCLC patients (pts), is sensitive to MET inhibition. We report interim data from Cohort A of the phase II VISION study (NCT02864992) of tepotinib, an oral potent highly selective MET inhibitor in NSCLC pts with METex14 skipping.
Pts with advanced wt EGFR/ALK NSCLC and METex14 skipping identified by liquid (L+) or tumor (T+) biopsy enrolled at 124 sites in 11 countries (35 in Asia: Japan [from Dec 2016], Republic of Korea, Taiwan [from Oct 2018]) received tepotinib 500 mg once daily until progression, intolerable toxicity or withdrawal. Primary endpoint is objective response rate (ORR) by independent review (IRC). Secondary endpoints include investigator-assessed ORR (INV), duration of response (DOR), PFS and safety (CTCAE 4.0). Pts evaluable for ORR have ≥2 post-baseline assessments or have discontinued for any reason. Predefined analysis sets include pts who are L+ or T+.
As of 14 June 2019, 1071 of 5102 prescreened pts were from Asia, 28 had been enrolled (17 Japan, 8 Korea, 3 Taiwan). At data cutoff (18 Feb 19) for efficacy and safety analyses, 87 pts had received tepotinib, treatment was ongoing in 47. In evaluable pts, ORR was 45–55% (Table). mDOR was >1 year in all groups (12.4–17.1 months) and >50% of pts were event free at 12 months (55–70%). mPFS was 9.5–12.2 months. 14 pts were from Asia (all from Japan), treatment was ongoing in 8. Of 11 evaluable pts from Japan, 6 were L+, 9 were T + (with overlap). In L+ pts, confirmed ORR (95% CI) was 66.7% (22.3, 95.7) by IRC and 83.3% (35.9, 99.6) by INV. In T+ pts, it was 33.3% (7.5, 70.1) by IRC, 55.6% (21.2, 86.3) by INV. Any/grade 3 treatment-related adverse events (TRAEs) reported by ≥ 15% of 87 treated pts were peripheral edema (48.3/8.0%), nausea (23.0/0%), diarrhea (20.7/1.1%). No TRAEs were grade 4/5. The safety profile was similar in pts from Japan. ORR: confirmed complete response/partial response. Patients evaluable for ORR have ≥2 post-baseline assessments or have discontinued for any reason. CI, confidence interval; ne, not estimable.L + T + IRC Inv n = 47 IRC n = 51 Inv n = 51 n = 48 ORR,* n (%) 24 (50.0) 26 (55.3) 23 (45.1) 28 (54.9) 95% CI 35.2, 64.8 40.1, 69.8 31.1, 59.7 40.3, 68.9 mDOR, months 95% CI 12.4 17.1 15.7 14.3 5.8, ne 7.1, ne 9.0, ne 5.7, ne 12-month event-free rate 95% CI 58% 55% 70% 59% 30, 78 28, 76 40, 87 32, 79 n = 57 n = 58 PFS events 22 24 23 22 mPFS, months 95% CI 9.5 9.5 10.8 12.2 6.7, ne 5.3, 21.1 6.9, ne 6.3, ne 12-month event-free rate 39% 42% 49% 55% 95% CI 21, 56 25, 58 31, 64 39, 69
Tepotinib has durable clinical activity and an acceptable safety profile in NSCLC pts with METex14 skipping detected by liquid or tissue biopsy.
NCT02864992.
Medical writing assistance (funded by Merck KGaA, Darmstadt, Germany) was provided by Matthew deSchoolmeester, PhD of Bioscript Science (Macclesfield, UK).
Merck KGaA.
Merck KGaA.
K. Park: Advisory / Consultancy: AstraZeneca, Boehringer Ingelheim, Clovis; Elli Lilly; Hanmi; ONO; Roche; Novartis. E. Felip: Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Merck KGaA; Advisory / Consultancy, Speaker Bureau / Expert testimony: AbbVie; Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca; Advisory / Consultancy: Blueprint Medicines; Research grant / Funding (institution): EMD Serono; Advisory / Consultancy, Speaker Bureau / Expert testimony: Boehringer Ingelheim; Advisory / Consultancy, Speaker Bureau / Expert testimony: BMS; Advisory / Consultancy, Speaker Bureau / Expert testimony: Eli Lilly; Advisory / Consultancy: Celgene, Guardant Health; Speaker Bureau / Expert testimony: MSD, Novartis, Pfizer, Roche, Takeda. R. Veillon: Research grant / Funding (institution): Takeda, AbbVie, Merck KGaA, BMS; Advisory / Consultancy, Speaker Bureau / Expert testimony: MSD; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Roche; Speaker Bureau / Expert testimony: DMS; Advisory / Consultancy: Pfizer, Novartis. A. Cortot: Research grant / Funding (institution): Merck KGaA; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Novartis; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: AstraZeneca; Honoraria (self), Advisory / Consultancy: BMS; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer; Honoraria (self), Travel / Accommodation / Expenses: MSD; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Takeda. J. Mazieres: Advisory / Consultancy: Roche, BMS, MSD, AstraZeneca, Pfizer, Novartis. H. Sakai: Speaker Bureau / Expert testimony, Research grant / Funding (institution): BMS, Ono, Chugai, MSD, Lilly, AstraZeneca; Research grant / Funding (institution): Merck KGaA, Regeneron, Taiho. N. Reinmuth: Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Boehringer Ingelheim; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Takeda; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: BMS; Advisory / Consultancy, Speaker Bureau / Expert testimony: AbbVie; Advisory / Consultancy: Merck KGaA; Advisory / Consultancy, Speaker Bureau / Expert testimony: MSD; Advisory / Consultancy, Speaker Bureau / Expert testimony: Pfizer. J-Y. Han: Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Research grant / Funding (institution): Roche; Honoraria (self), Advisory / Consultancy: BMS; Honoraria (self), Advisory / Consultancy: MSD; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Takeda; Advisory / Consultancy: Lilly; Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Advisory / Consultancy: Novartis; Research grant / Funding (institution): ONO. M. Morise: Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Chugai; Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Pfizer; Honoraria (self), Travel / Accommodation / Expenses: Eli Lilly; Honoraria (self), Travel / Accommodation / Expenses: MSD; Honoraria (self), Research grant / Funding (institution): Ono; Honoraria (self), Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Taiho, Boehringer Ingelheim, Novartis, EMD, Kissei. T. Tokito: Honoraria (self): MSD, Chu-gai, Ono, Boehringer Ingelheim, Pfizer; Honoraria (self), Advisory / Consultancy: AstraZeneca. R. Bruns: Full / Part-time employment: Merck KGaA. J. Scheele: Full / Part-time employment: Merck KGaA. J. Straub: Full / Part-time employment: Merck KGaA. X. Le: Advisory / Consultancy: AstraZeneca, Lilly. P.K. Paik: Research grant / Funding (self), Research grant / Funding (institution): EMD Serono; Advisory / Consultancy, Research grant / Funding (institution): Celgene; Advisory / Consultancy: AbbVie, BMS, Lilly, Takeda. All other authors have declared no conflicts of interest.