1254P - Efficacy and safety of tepotinib in patients (pts) with advanced age: VISION subgroup analysis of pts with MET exon 14 (METex14) skipping NSCLC

Background

The pt population defined by METex14 skipping is typically elderly, and may be challenging to treat due to comorbidities. In the VISION study (median age 73.1 years [yr; range 41–94]), the selective MET inhibitor tepotinib had an objective response rate of 44.7%, and median duration of response of 11.1 months. We investigated outcomes according to age.

Methods

Pts with advanced METex14 skipping NSCLC received 500 mg (450 mg active moiety) tepotinib orally once daily. All pts who received tepotinib in Cohorts A (primary analysis) and C (confirmatory) were assessed for safety; pts in Cohort A were assessed for efficacy. Primary endpoint was objective response by independent review committee. Secondary endpoints included duration of response, and safety. Subgroup analysis according to age was predefined.

Results

A total of 152 pts were enrolled in Cohort A. Baseline characteristics were similar in pts <75/≥75 yr (n=84/68): 52.4/51.5% were male, 60.7/41.2% had a history of smoking, 70.2/76.5% had ECOG PS 1, 89.3/82.4% had adenocarcinoma histology, and 44.0/47.1% were treatment-naïve. Efficacy in pts <75 or ≥75 yr is shown (Table). Of 124 patients who discontinued tepotinib, 47 received subsequent treatments; the majority were <75 yr (n=36; 76.6%). A total of 255 pts were assessed for safety. In pts <75/≥75 yr (n=146/109), treatment-related adverse events (TRAEs) occurred in 87.7/84.4%, Grade ≥3 TRAEs occurred in 18.5/33.9%, and TRAEs led to discontinuation in 7.5/14.7%. The most common TRAE, peripheral edema, occurred in 56.2% of pts <75, and 51.4% of pts ≥75 yr. Table: 1254P

Data cut-off: July 1, 2020.CI, confidence interval; IRC, independent review committee.

Conclusions

Tepotinib demonstrated robust and durable efficacy in elderly pts, with a manageable safety profile, and a low proportion of TRAEs leading to discontinuation. Given the vulnerability of pts of advanced age, prioritization of effective and convenient targeted therapies in this population is warranted.

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

M.C.C. Garassino: Financial Interests, Personal, Other, Honoraria: MSD Oncology; Financial Interests, Personal, Other, Honoraria: AstraZeneca/MedImmune; Financial Interests, Personal, Other, Honoraria: GlaxoSmithKline; Financial Interests, Personal, Other, Honoraria: Takeda; Financial Interests, Personal, Other, Honoraria: Roche; Financial Interests, Personal, Other, Honoraria: Bristol Myers Squibb; Financial Interests, Personal, Advisory Role: Bristol Myers Squibb; Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Takeda; Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Advisory Role: Tiziana Life Sciences; Financial Interests, Personal, Advisory Role: Sanofi-Aventis; Financial Interests, Personal, Advisory Role: Celgene; Financial Interests, Personal, Advisory Role: Daiichi Sankyo; Financial Interests, Personal, Advisory Role: Inivata; Financial Interests, Personal, Advisory Role: Incyte; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: Seattle Genetics; Financial Interests, Personal, Advisory Role: Eli Lilly; Financial Interests, Personal, Advisory Role: GlaxoSmithKline; Financial Interests, Personal, Advisory Role: Bayer Healthcare Pharmaceuticals; Financial Interests, Personal, Advisory Role: Blueprint Medicines; Financial Interests, Personal, Advisory Role: Janssen; Financial Interests, Personal, Advisory Role: Regeneron; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: Takeda; Financial Interests, Personal, Speaker’s Bureau: MSD Oncology; Financial Interests, Personal, Speaker’s Bureau: Celgene; Financial Interests, Personal, Speaker’s Bureau: Incyte; Financial Interests, Personal, Speaker’s Bureau: Roche; Financial Interests, Personal, Speaker’s Bureau: Bristol Myers Squibb; Financial Interests, Personal, Speaker’s Bureau: Otsuka; Financial Interests, Personal, Speaker’s Bureau: Eli Lilly; Financial Interests, Institutional, Funding, for Research: Bristol Myers Squibb; Financial Interests, Institutional, Funding, for Research: MSD; Financial Interests, Institutional, Funding, for Research: Roche/Genentech; Financial Interests, Institutional, Funding, for Research: AstraZeneca/MedImmune; Financial Interests, Institutional, Funding, for Research: AstraZeneca; Financial Interests, Institutional, Funding, for Research: Pfizer; Financial Interests, Institutional, Funding, for Research: GlaxoSmithKline; Financial Interests, Institutional, Funding, for Research: Novartis; Financial Interests, Institutional, Funding, for Research: Merck; Financial Interests, Institutional, Funding, for Research: Incyte; Financial Interests, Institutional, Funding, for Research: Takeda; Financial Interests, Institutional, Funding, for Research: Spectrum Pharmaceuticals; Financial Interests, Institutional, Funding, for Research: Blueprint Medicines; Financial Interests, Institutional, Funding, for Research: Eli Lilly; Financial Interests, Institutional, Funding, for Research: AstraZeneca; Financial Interests, Institutional, Funding, for Research: Ipsen; Financial Interests, Institutional, Funding, for Research: Janssen; Financial Interests, Institutional, Funding, for Research: Exelixis; Financial Interests, Institutional, Funding, for Research: MedImmune; Financial Interests, Institutional, Funding, for Research: Sanofi; Financial Interests, Institutional, Funding, for Research: Pfizer; Financial Interests, Institutional, Funding, for Research: Amgen; Financial Interests, Personal, Other, Travel, accommodation, expenses: Pfizer; Financial Interests, Personal, Other, Travel, accommodation, expenses: Roche; Financial Interests, Personal, Other, Travel, accommodation, expenses: AstraZeneca. E. Felip: Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Advisory Role: Boehringer Ingelheim; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Bristol Myers Squibb; Financial Interests, Personal, Advisory Role: Guardant Health; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Takeda; Financial Interests, Personal, Advisory Role: AbbVie; Financial Interests, Personal, Advisory Role: Blueprint Medicines; Financial Interests, Personal, Advisory Role: Lilly; Financial Interests, Personal, Advisory Role: Merck KGaA; Financial Interests, Personal, Advisory Role: Merck Sharp & Dohme; Financial Interests, Personal, Advisory Role: Janssen; Financial Interests, Personal, Advisory Role: Samsung; Financial Interests, Personal, Speaker’s Bureau, and expert testimony: Pfizer; Financial Interests, Personal, Speaker’s Bureau, and expert testimony: Roche; Financial Interests, Personal, Speaker’s Bureau, and expert testimony: AstraZeneca; Financial Interests, Personal, Speaker’s Bureau, and expert testimony: Bristol Myers Squibb; Financial Interests, Personal, Speaker’s Bureau, and expert testimony: Novartis; Financial Interests, Personal, Speaker’s Bureau, and expert testimony: Takeda; Financial Interests, Personal, Speaker’s Bureau, and expert testimony: Lilly; Financial Interests, Personal, Speaker’s Bureau, and expert testimony: Merck Sharp & Dohme; Financial Interests, Personal, Speaker’s Bureau, and expert testimony: Medscape; Financial Interests, Personal, Speaker’s Bureau, and expert testimony: prIME Oncology; Financial Interests, Personal, Speaker’s Bureau, and expert testimony: Touchtime; Financial Interests, Personal, Research Grant: Fundación Merck Salud; Financial Interests, Personal, Research Grant: Grant for Oncology Innovation (GOI); Financial Interests, Personal, Member of the Board of Directors, Independent Member: Grifols. H. Sakai: Financial Interests, Personal, Speaker’s Bureau: BMS; Financial Interests, Personal, Speaker’s Bureau: Ono Pharmaceutical; Financial Interests, Personal, Speaker’s Bureau: MSD K.K.; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: Chugai Pharma; Financial Interests, Personal, Speaker’s Bureau: Taiho Pharmaceutical; Financial Interests, Personal, Speaker’s Bureau: Boehringer Ingelheim; Financial Interests, Personal, Speaker’s Bureau: Merck KGaA. X. Le: Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Eli Lilly; Financial Interests, Personal, Advisory Role: EMD Serono; Financial Interests, Personal, Funding, for Research: Eli Lilly; Financial Interests, Personal, Funding, for Research: Boehringer Ingelheim. R. Veillon: Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Speaker’s Bureau: MSD; Financial Interests, Personal, Speaker’s Bureau: BMS; Financial Interests, Personal, Speaker’s Bureau: Roche; Financial Interests, Personal, Funding, for Research: Roche; Financial Interests, Personal, Funding, for Research: Takeda; Financial Interests, Personal, Funding, for Research: AbbVie; Financial Interests, Personal, Funding, for Research: Merck; Financial Interests, Personal, Funding, for Research: BMS. E.F.F. Smit: Financial Interests, Institutional, Advisory Role: Lilly; Financial Interests, Institutional, Advisory Role: AstraZeneca; Financial Interests, Institutional, Advisory Role: Boehringer Ingelheim; Financial Interests, Institutional, Advisory Role: Roche/Genentech; Financial Interests, Institutional, Advisory Role: Bristol Myers Squibb; Financial Interests, Institutional, Advisory Role: Merck KGaA; Financial Interests, Institutional, Advisory Role: MSD Oncology; Financial Interests, Institutional, Advisory Role: Takeda; Financial Interests, Institutional, Advisory Role: Bayer; Financial Interests, Institutional, Advisory Role: Regeneron; Financial Interests, Institutional, Advisory Role: Novartis; Financial Interests, Institutional, Advisory Role: Daiichi Sankyo; Financial Interests, Institutional, Advisory Role: Seattle Genetics; Financial Interests, Institutional, Funding, for Research: Boehringer Ingelheim; Financial Interests, Institutional, Funding, for Research: Bayer; Financial Interests, Institutional, Funding, for Research: Roche/Genentech; Financial Interests, Institutional, Funding, for Research: AstraZeneca; Financial Interests, Institutional, Funding, for Research: Bristol Myers Squibb. J. Mazieres: Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Novartis. A.B. Cortot: Financial Interests, Personal, Funding, for Research: Merck KGaA; Financial Interests, Personal, Funding, for Research: Novartis; Financial Interests, Personal, Other, Honoraria: AstraZeneca; Financial Interests, Personal, Other, Honoraria: BMS; Financial Interests, Personal, Other, Honoraria: Novartis; Financial Interests, Personal, Other, Honoraria: MSD; Financial Interests, Personal, Other, Honoraria: Pfizer; Financial Interests, Personal, Other, Honoraria: Roche; Financial Interests, Personal, Other, Honoraria: Takeda; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: BMS; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Advisory Role: Takeda; Financial Interests, Personal, Other, Travel expenses: AstraZeneca; Financial Interests, Personal, Other, Travel expenses: MSD; Financial Interests, Personal, Other, Travel expenses: Novartis; Financial Interests, Personal, Other, Travel expenses: Pfizer; Financial Interests, Personal, Other, Travel expenses: Roche; Financial Interests, Personal, Other, Travel expenses: Takeda. J. Raskin: Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: Lilly; Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim; Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Other, Travel expenses: Roche. M. Thomas: Financial Interests, Personal, Other, Honoraria (Scientific meetings) and travel support: BMS; Financial Interests, Personal, Other, Honoraria (Scientific meetings) and travel support: MSD; Financial Interests, Personal, Other, Honoraria (Scientific meetings) and travel support: AstraZeneca; Financial Interests, Personal, Other, Honoraria (Scientific meetings) and travel support: Novartis; Financial Interests, Personal, Other, Honoraria (Scientific meetings) and travel support: Roche; Financial Interests, Personal, Other, Honoraria (Scientific meetings) and travel support: Takeda; Financial Interests, Personal, Other, Honoraria (Scientific meetings) and travel support: Lilly; Financial Interests, Personal, Other, Honoraria (Scientific meetings) and travel support: Chugai; Financial Interests, Personal, Other, Honoraria (Scientific meetings) and travel support: Celgene; Financial Interests, Personal, Other, Honoraria (Scientific meetings) and travel support: Boehringer Ingelheim; Financial Interests, Personal, Other, Honoraria (Scientific meetings) and travel support: Pfizer; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Takeda; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Advisory Board: Boehringer Ingelheim; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Institutional, Funding, for Research: BMS; Financial Interests, Institutional, Funding, for Research: AstraZeneca; Financial Interests, Institutional, Funding, for Research: Roche; Financial Interests, Institutional, Funding, for Research: Takeda. S. Viteri: Financial Interests, Personal, Advisory Role: AbbVie; Financial Interests, Personal, Advisory Role: BMS; Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Speaker’s Bureau: BMS; Financial Interests, Personal, Speaker’s Bureau: MSD; Financial Interests, Personal, Speaker’s Bureau: Roche; Financial Interests, Personal, Other, Travel expenses: Roche; Financial Interests, Personal, Other, Travel expenses: OSE Pharma; Financial Interests, Personal, Other, Travel expenses: BMS; Financial Interests, Personal, Other, Travel expenses: Merck; Financial Interests, Personal, Other, Travel expenses: Merck Serono; Financial Interests, Personal, Other, Travel expenses: Puma Biotechnology; Financial Interests, Personal, Other, Travel expenses: Janssen Cilag. W.T. Iams: Financial Interests, Personal, Other, Consulting fees: Genentech; Financial Interests, Personal, Other, Consulting fees: Jazz Pharma; Financial Interests, Personal, Other, Consulting fees: G1 Therapeutics; Financial Interests, Personal, Speaker’s Bureau: OncLive; Financial Interests, Personal, Speaker’s Bureau: Clinical Care Options; Financial Interests, Personal, Other, Travel expenses: EMD Serono. H.R. Kim: Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Bristol Myers Squibb; Financial Interests, Personal, Other, Honoraria: AstraZeneca; Financial Interests, Personal, Other, Honoraria: Bristol Myers Squibb; Financial Interests, Personal, Other, Honoraria: Ono Pharmaceutical; Financial Interests, Personal, Other, Honoraria: Roche. K. Berghoff: Financial Interests, Personal, Full or part-time Employment: Merck KGaA. R. Bruns: Financial Interests, Personal, Full or part-time Employment: Merck KGaA; Financial Interests, Personal, Stocks/Shares: Merck KGaA. G. Otto: Financial Interests, Personal, Full or part-time Employment: Merck KGaA. P.K. Paik: Financial Interests, Personal, Advisory Role: AbbVie; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Calithera; Financial Interests, Personal, Advisory Role: Celgene; Financial Interests, Personal, Advisory Role: Lilly; Financial Interests, Personal, Advisory Role: Takeda; Financial Interests, Personal, Advisory Role: EMD Serono; Financial Interests, Personal, Advisory Role: Xencor; Financial Interests, Personal, Advisory Role: Bicara; Financial Interests, Personal, Advisory Role: Boehringer Ingelheim; Financial Interests, Personal, Advisory Role: GlaxoSmithKline; Financial Interests, Personal, Advisory Role: EMD Serono; Financial Interests, Institutional, Other, research expenses: Celgene; Financial Interests, Institutional, Other, research expenses: EMD Serono. All other authors have declared no conflicts of interest.