1380P - Treatment (Tx) sequencing with tepotinib in previously treated patients (pts) with MET exon 14 (METex14) skipping NSCLC in the VISION trial

Background

Tepotinib, a MET TKI, is approved for Tx of advanced/metastatic METex14 skipping NSCLC, after immunotherapy (IO) and/or platinum (plat)-based chemotherapy (CT) in the EU, and regardless of prior Tx in other countries including the UK and Switzerland. In the VISION trial, tepotinib showed durable activity regardless of prior Tx, including in first line (1L) (1L outcomes: ORR, 56.1%; mDOR, 46.4 mo; and mPFS, 12.6 mo). We report long-term efficacy in previously treated pts (i.e. in second [2L], second or later [2L+], and third or later [3L+] lines) and prior/post-tepotinib Tx (data cut-off: Nov 20, 2022).

Methods

Pts received tepotinib 500 mg (450 mg active moiety) QD. Primary endpoint was objective response (RECIST v1.1) by IRC. Prior/post-tepotinib Tx was investigator’s choice; outcomes were reported per investigator.

Results

Of 313 pts, 149 received tepotinib as 2L+ Tx (median age, 70.8 years), including 92 in 2L (median age, 70.4) and 57 in 3L+ (median age, 71.9). Across all prior Tx lines, ORR was 28.9%, mDOR was 6.0 mo, and mPFS was 5.0 mo. Outcomes were similar across prior regimens, including plat-based CT without IO (n=99), IO monotherapy (n=59), and IO+CT (n=22; Table). Compared with prior Tx, tepotinib outcomes in 2L+ were greatly improved (ORR, 45.0%; mDOR, 12.6 mo; mPFS, 11.0 mo) and were consistent regardless of Tx line (2L, 3L+) or smoking history. At the data cut-off, 139 (93.3%) 2L+ pts had discontinued tepotinib, and 70/139 (50.4%) had started subsequent Tx, including plat-based CT without IO (n=16), IO monotherapy (n=22), IO+CT (n=4), and MET TKIs (n=34). Across all subsequent MET TKIs after 2L+ tepotinib, best response was PR in 2 and SD in 10 pts. Table: 1380P

*mDOR and mPFS were based on a descriptive analysis. CT, chemotherapy; DOR, duration of response; IO, immunotherapy; IRC, independent review committee; m, median; mo, months; ORR, objective response rate; PFS, progression-free survival; pts, patients; Tx, treatment.

Conclusions

Tepotinib showed clinically meaningful efficacy in 2L+, 2L and 3L+, which was far greater than with standard of care Tx in prior lines. Despite pre-tepotinib Tx, a high proportion of 2L+ pts went on to receive post-tepotinib Tx, often including MET TKIs.

Clinical trial identification

NCT02864992.

Editorial acknowledgement

Medical writing assistance (funded by Merck Healthcare KGaA, Darmstadt, Germany) was provided by Moon Jain, PhD of Syneos Health, London, UK.

Legal entity responsible for the study

Merck Healthcare KGaA.

Funding

Merck Healthcare KGaA, Darmstadt, Germany (CrossRef Funder ID: 10.13039/100009945).

Disclosure

S. Viteri: Financial Interests, Personal, Advisory Role: AbbVie, Bristol Myers Squibb, Roche, Takeda, AstraZeneca, MSD; Financial Interests, Personal, Speaker’s Bureau: Bristol Myers Squibb, Merck Sharpe & Dohme, Roche, AstraZeneca; Financial Interests, Personal, Other, travel expenses: Roche, OSE Pharma, BMS, MSD, Merck Healthcare KGaA, Darmstadt, Germany, Puma Biotechnology, Janssen Cilag. E. Felip: Financial Interests, Personal, Advisory Role: Pfizer, Roche, Boehringer Ingelheim, AstraZeneca, Bristol Myers Squibb, Guardant Health, Novartis, Takeda, AbbVie, Blueprint Medicines, Lilly, Merck Healthcare KGaA, Darmstadt, Germany, Merck Sharp & Dohme, Janssen, Samsung; Financial Interests, Personal, Other, Speaker’s bureau/expert testimony: Pfizer, Roche, AstraZeneca, Bristol Myers Squibb, Novartis, Takeda, Lilly, Merck Sharp & Dohme, Medscape, prIME Oncology, Touchtime; Financial Interests, Personal, Research Grant: Fundación Merck Salud, a private non-profit institution founded by Merck, S.L.U., Madrid, Spain, an affiliate of Merck KGaA, Grant for Oncology Innovation (GOI); Financial Interests, Personal, Other, Officer/Board of Directors: Grifols (Independent Member). F. Griesinger: Financial Interests, Personal, Advisory Role: Amgen, AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Celgene, GSK, Lilly, MSD, Novartis, Pfizer, Roche, Siemens, Takeda; Financial Interests, Personal, Other, Honoraria: Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, BMS, Celgene, GSK, Lilly, MSD, Novartis, Pfizer, Roche, Siemens, Takeda; Financial Interests, Personal, Research Grant: Amgen, AstraZeneca, Boehringer Ingelheim, BMS, Celgene, GSK, Lilly, MSD, Novartis, Pfizer, Roche, Siemens, Takeda. M.C. Garassino: Financial Interests, Personal, Other, Honoraria: MSD Oncology, AstraZeneca/MedImmune, GSK, Takeda, Roche, Bristol Myers Squibb; Financial Interests, Personal, Advisory Role: Bristol Myers Squibb, MSD, AstraZeneca, Novartis, Takeda, Roche, Tiziana Life Sciences, Sanofi-Aventis, Celgene, Daiichi Sankyo, Inivata, Incyte, Pfizer, Seattle Genetics, Eli Lilly, GSK, Bayer Healthcare Pharmaceuticals, Blueprint Medicines, Janssen, Regeneron; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Takeda, MSD Oncology, Celgene, Incyte, Roche, Bristol Myers Squibb, Otsuka, Eli Lilly; Financial Interests, Institutional, Research Funding: Bristol Myers Squibb, MSD, Roche/Genentech, AstraZeneca/MedImmune, AstraZeneca, Pfizer, GSK, Novartis, Merck Healthcare KGaA, Darmstadt, Germany, Incyte, Takeda, Spectrum Pharmaceuticals, Blueprint Medicines, Eli Lilly, Ipsen, Janssen, Exelixis, MedImmune, Sanofi, Pfizer, Amgen; Financial Interests, Personal, Other, Travel, accommodation, expenses: Pfizer; Financial Interests, Other, Travel, accommodation, expenses: Roche, AstraZeneca. H. Sakai: Financial Interests, Personal, Speaker’s Bureau: Bristol Myers Squibb, Ono Pharmaceutical, MSD K.K., AstraZeneca, Chugai Pharma, Taiho Pharmaceutical, Boehringer Ingelheim. X. Le: Financial Interests, Personal, Advisory Role: AstraZeneca, Eli Lilly, EMD Serono, an affiliate of Merck KGaA, Novartis, Daiichi Sankyo, Hengrui Therapeutics; Financial Interests, Personal, Research Funding: Eli Lilly, Boehringer Ingelheim. R. Veillon: Financial Interests, Personal, Advisory Role: MSD, Pfizer, Novartis; Financial Interests, Personal, Speaker’s Bureau: MSD, Bristol Myers Squibb, Roche; Financial Interests, Personal, Research Funding: Roche, Takeda, AbbVie, Merck Healthcare KGaA, Darmstadt, Germany, Bristol Myers Squibb . E.F. Smit: Financial Interests, Institutional, Advisory Role: Lilly, AstraZeneca, Boehringer Ingelheim, Roche/Genentech, Bristol Myers Squibb, Merck Healthcare KGaA, Darmstadt, Germany, MSD Oncology, Takeda, Bayer, Regeneron, Novartis, Daiichi Sankyo, Seattle Genetics. J. Raskin: Financial Interests, Personal, Advisory Role: Pfizer, Lilly; Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim, Bristol Myers Squibb; Financial Interests, Personal, Other, Travel expenses: Roche. M. Thomas: Financial Interests, Personal, Other, Honoraria – Scientific Meetings: AbbVie, Bristol Myers Squibb, MSD, AstraZeneca, Novartis, Roche, Takeda, Lilly, Chugai, Celgene, Boehringer Ingelheim, Pfizer, Janssen, GSK, Merck Healthcare KGaA, Darmstadt, Germany, Sanofi, Amgen; Financial Interests, Personal, Other, Travelling support: AbbVie, Bristol Myers Squibb, MSD, AstraZeneca, Novartis, Roche, Takeda, Lilly, Chugai Pharma, Celgene, Boehringer Ingelheim, Pfizer; Financial Interests, Personal, Advisory Board: AbbVie, Bristol Myers Squibb, MSD, AstraZeneca, Novartis, Roche, Takeda, Lilly, Chugai Pharma, Celgene, Boehringer Ingelheim, Pfizer, Janssen, Daiichi Sankyo, GSK, Merck Healthcare KGaA, Darmstadt, Germany, Sanofi, Amgen; Financial Interests, Institutional, Research Funding: Bristol Myers Squibb, AstraZeneca, Roche, Takeda. M. Ahn: Financial Interests, Personal, Advisory Role: AstraZeneca, Lilly, Amgen, Merck Healthcare KGaA, Darmstadt, Germany, MSD, Takeda, Ono, Pfizer, Yuhan, Alpha-Pharmaceuticals, Daiichi Sankyo, Roche. S. Vlassak: Financial Interests, Personal, Full or part-time Employment: Merck N.V. S.A., Belgium, an affiliate of Merck 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. A. Johne: Financial Interests, Personal, Full or part-time Employment: Merck Healthcare KGaA, Darmstadt, Germany; Financial Interests, Personal, Stocks/Shares: Novartis. P.K. Paik: Financial Interests, Personal, Advisory Role: Takeda, Xencor, CrownBio, Bicara, Mirati, EMD Serono, an affiliate of Merck KGaA; Financial Interests, Institutional, Research Grant: Bicara, Calithera, EMD Serono, an affiliate of Merck KGaA.