Abstract 1283P
Background
The multi-cohort phase II VISION study investigates tepotinib in pts with NSCLC with MET alterations, and is the largest study of pts with METex14 skipping detected by liquid (L+) or tissue (T+) biopsy. Here we report efficacy outcomes in the overall intention-to-treat population.
Methods
Pts with advanced, EGFR/ALK wild-type, METex14 skipping NSCLC received oral tepotinib 500 mg once daily. Evaluable pts for objective response rate (ORR) had ≥2 post-baseline assessments or discontinuation for any reason. Primary endpoint: ORR by independent review committee (IRC). Secondary endpoints: investigator-assessed (INV) ORR, duration of response (DOR), progression-free survival (PFS), and safety. Objective responses were confirmed by two scans ≥4 weeks apart. Subgroup analyses were preplanned.
Results
By data cut-off (01 Jan 2020), Cohort A had enrolled 152 pts: 52% male, median age 73 years (range 41–94), 43% non-smokers, 55% had received prior treatment for advanced/ metastatic disease. Overall ORR (95% CI) in evaluable pts (n=146; 95 L+ and 84 T+) was 44.5% (36.3, 53.0) by IRC and 54.8% (46.4, 63.0) by INV. ORR was consistent across subgroups, supporting robustness of efficacy (Table). Median DOR (95% CI) in L+ pts was 9.9 months (7.2, not estimable [ne]) by IRC and 14.0 months (7.2, ne) by INV, and in T+ pts was 12.4 months (9.7, ne) by IRC and 16.4 months (9.7, ne) by INV. Median PFS in L+ pts was 8.5 months (6.7, 10.9) by IRC and 8.5 months (5.8, 11.0) by INV, and in T+ pts was 11.0 months (7.8, 17.1) by IRC and 12.2 months (6.8, 19.6) by INV. Grade ≥3 treatment-related adverse events (TRAEs) were reported by 27.6% of pts; 17 (11.2%) discontinued due to TRAEs, mostly peripheral edema (4.6%). The safety profile was similar across subgroups. Table: 1283P
| ORR, % (95% CI) | IRC | INV |
| L+ | 47.4 (37.0, 57.9) | 54.7 (44.2, 65.0) |
| T+ | 45.2 (34.3, 56.5) | 58.3 (47.1, 69.0) |
| Gender | ||
| M | 46.1 (34.5, 57.9) | 52.6 (40.8, 64.2) |
| F | 42.9 (31.1, 55.3) | 57.1 (44.7, 68.9) |
| Age | ||
| <75 | 50.0 (38.6, 61.4) | 56.3 (44.7, 67.3) |
| ≥75 | 37.9 (26.2, 50.7) | 53.0 (40.3, 65.4) |
| Race | ||
| Caucasian | 43.1 (33.4, 53.3) | 52.0 (41.8, 62.0) |
| Asian | 47.4 (31.0, 64.2) | 60.5 (43.4, 76.0) |
| ECOG PS | ||
| 0 | 59.5 (42.1, 75.2) | 56.8 (39.5, 72.9) |
| 1 | 39.4 (30.2, 49.3) | 54.1 (44.3, 63.7) |
| Smoker | ||
| Y | 51.3 (39.6, 63.0) | 51.3 (39.6, 63.0) |
| N | 35.5 (23.7, 48.7) | 56.5 (43.3, 69.0) |
| Therapy line | ||
| 1 | 44.6 (32.3, 57.5) | 52.3 (39.5, 64.9) |
| ≥2 | 44.4 (33.4, 55.9) | 56.8(45.3, 67.8) |
| Prior platinum-based therapy | ||
| Y | 48.6 (36.7, 60.7) | 58.3 (46.1, 69.8) |
| N | 42.3 (30.6, 54.6) | 50.7 (38.6, 62.8) |
Conclusions
Tepotinib has durable clinical activity across subgroups and manageable toxicity in the largest study of pts with METex14 skipping NSCLC identified by L+ or T+.
Clinical trial identification
NCT02864992.
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. Mazieres: Advisory/Consultancy: Roche; Advisory/Consultancy: BMS; Advisory/Consultancy: MSD; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Novartis. P.K. 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. E. Felip: Advisory/Consultancy, Speaker Bureau/Expert testimony: Pfizer; Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche; Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy, Speaker Bureau/Expert testimony: AstraZeneca; Advisory/Consultancy, Speaker Bureau/Expert testimony: BMS; Advisory/Consultancy: Guardant Health; Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis; Advisory/Consultancy, Speaker Bureau/Expert testimony: Takeda; Advisory/Consultancy: AbbVie; Advisory/Consultancy: Blueprint Medicines; Advisory/Consultancy, Speaker Bureau/Expert testimony: Lilly; Advisory/Consultancy: Merck KGaA; Advisory/Consultancy, Speaker Bureau/Expert testimony: Merck Sharp & Dohme; Advisory/Consultancy: Janssen; Advisory/Consultancy: Samsung; Speaker Bureau/Expert testimony: Medscape; Speaker Bureau/Expert testimony: prIME Oncology; Speaker Bureau/Expert testimony: Touchtime; Research grant/Funding (self): Fundación Merck Salud; Research grant/Funding (self): Grant for Oncology Innovation (GOI); Officer/Board of Directors: Grifols (Independent Member). R. Veillon: Advisory/Consultancy, Speaker Bureau/Expert testimony: MSD; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Novartis; Speaker Bureau/Expert testimony, Research grant/Funding (self): BMS; Speaker Bureau/Expert testimony, Research grant/Funding (self): Roche; Research grant/Funding (self): Takeda; Research grant/Funding (self): AbbVie; Research grant/Funding (self): Merck. 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. A.B. Cortot: Research grant/Funding (self): Merck KGaA; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Novartis; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self), Advisory/Consultancy: BMS; Honoraria (self), Travel/Accommodation/Expenses: MSD; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Takeda. S. Viteri: Advisory/Consultancy: AbbVie; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: BMS; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Roche; Speaker Bureau/Expert testimony: MSD; Travel/Accommodation/Expenses: OSE Pharma; Travel/Accommodation/Expenses: Merck. M.C. Garassino: Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy: Novartis; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Seattle Genetics; Advisory/Consultancy: Daiichi Sankyo; Advisory/Consultancy: Sanofi; Speaker Bureau/Expert testimony: Otsuka Pharma; Speaker Bureau/Expert testimony: Incyte; Advisory/Consultancy, Speaker Bureau/Expert testimony: Eli Lilly; Advisory/Consultancy, Speaker Bureau/Expert testimony: BMS; Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche; Advisory/Consultancy, Speaker Bureau/Expert testimony: Celgene; Advisory/Consultancy, Speaker Bureau/Expert testimony: Takeda; Advisory/Consultancy, Speaker Bureau/Expert testimony, steering committee: MSD; Advisory/Consultancy, Speaker Bureau/Expert testimony, steering committee: AstraZeneca; Honoraria (self), Advisory/Consultancy, honoraria for speaker: Takeda. J.P. Van Meerbeeck: Advisory/Consultancy: Amgen; Travel/Accommodation/Expenses: BMS. J. Raskin: Advisory/Consultancy: Pfizer; Advisory/Consultancy: Lilly; Speaker Bureau/Expert testimony: Boehringer Ingelheim; Speaker Bureau/Expert testimony: BMS; Travel/Accommodation/Expenses: Roche. M. Thomas: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses, Honoraria – Scientific Meetings (self): BMS; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses, Honoraria – Scientific Meetings (self): MSD; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses, Honoraria – Scientific Meetings (self): AstraZeneca; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses, Honoraria – Scientific Meetings (self): Novartis; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses, Honoraria – Scientific Meetings (self): Roche; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses, Honoraria – Scientific Meetings (self): Lilly; Honoraria (self), Travel/Accommodation/Expenses, Honoraria – Scientific Meetings (self): Chugai; Honoraria (self), Travel/Accommodation/Expenses, Honoraria – Scientific Meetings (self): Celgene; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses, Honoraria – Scientific Meetings (self): Boehringer Ingelheim; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses, Honoraria – Scientific Meetings (self): Pfizer; Advisory/Consultancy, Research grant/Funding (institution): Takeda. M. Morise: Speaker Bureau/Expert testimony: Chugai; Speaker Bureau/Expert testimony: MSD; Speaker Bureau/Expert testimony: ONO; Speaker Bureau/Expert testimony: AstraZeneca. 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: Pfizer; Advisory/Consultancy: Eli Lilly; Advisory/Consultancy: Takeda; Shareholder/Stockholder/Stock options: TheraCanVac Inc; Shareholder/Stockholder/Stock options: Gencurix Inc; Shareholder/Stockholder/Stock options: Bridgebio Therapeutics. P. Conte: Speaker Bureau/Expert testimony, Research grant/Funding (self), Travel/Accommodation/Expenses: Novartis; Speaker Bureau/Expert testimony, Research grant/Funding (self): Roche; Research grant/Funding (self): Merck KGaA; Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: AstraZeneca; Travel/Accommodation/Expenses: Celgene; Travel/Accommodation/Expenses: Tesaro. R. Bruns: Full/Part-time employment: Merck KGaA, Darmstadt, Germany. T. Demuth: Full/Part-time employment: Merck KGaA, Darmstadt, Germany. K.M. Schumacher: Full/Part-time employment: Merck KGaA, Darmstadt, Germany. X. Le: Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Eli Lilly; Advisory/Consultancy: EMD Serono; Research grant/Funding (self): Eli Lilly; Research grant/Funding (self): Boehringer Ingelheim.