Abstract 34P
Background
Tepotinib is a MET TKI approved for METex14 skipping NSCLC. We report Tx sequencing prior/post tepotinib of immunotherapy (IO), chemotherapy (CT) and METi (post only) in VISION (data cut-off: Feb 20, 2022).
Methods
Pts with advanced/metastatic METex14 skipping NSCLC received 500 mg (450 mg active moiety) tepotinib QD. Primary endpoint: objective response (RECIST 1.1) by IRC. Prior/post tepotinib Tx was investigator's choice; outcomes were reported per investigator.
Results
Of 313 pts (median age 72), 164 were Tx naïve (median age 74) and 149 previously treated (median age 70.8). Among previously treated pts, the most common 1L regimen prior to enrolling in VISION was platinum-CT without IO (58%), then IO monotherapy (23%) and IO-CT (13%). Across all prior 1L regimens, median duration of Tx was 4 mo (IQR 1.8–7.3), with an ORR of 24.8%, mDOR of 6.0 mo (IQR 4–12) and mPFS of 4.0 mo (IQR 2–8.5) (outcomes by Tx regimen in table). In contrast, 1L outcomes to tepotinib were greatly improved with an ORR of 56.1%, mDOR of 46.4 mo and mPFS of 12.6 mo. Overall, 265 pts (84.7%) discontinued tepotinib; 124 pts (46.8%) received subsequent Tx. 48 pts received subsequent METi (20 crizotinib, 15 capmatinib, 4 bozitinib, 3 tepotinib, 3 amivantamab, 3 cabozantinib, 4 other; 4 pts received different METi in subsequent lines). 31 pts received subsequent METi immediately after tepotinib (11 1L and 20 2L+ pts). BOR across all subsequent METi was 3 PR (1 pt received METi immediately after tepotinib, 2 pts received CT/IO regimens followed by METi), 11 SD; longest mDOR and mPFS were 4.0 and 2.5 mo, respectively. Outcomes to subsequent CT/IO were comparable to outcomes of prior CT/IO as well as those reported in literature.
Table: 34P| Outcomes with: | No. pts receiving Tx | ORR, % | mDOR, mo | mPFS, mo |
|---|---|---|---|---|
| 1L Tx* prior to tepotinib by investigator assessment | ||||
| IO+platinum CT | 19 | 26.3 | 5.0 | 5.0 |
| IO mono | 34 | 23.5 | 7.5 | 5.0 |
| Platinum-CT without IO | 87 | 27.6 | 5.0 | 4.0 |
| Tepotinib by IRC | ||||
| 1L | 164 | 56.1 | 46.4 | 12.6 |
| 2L | 92 | 45.7 | 12.6 | 10.9 |
| +3L | 57 | 43.9 | 10.8 | 11.0 |
| Post tepotinib Tx by investigator assessment | ||||
| Subsequent CT | 31 | 6.5 | 3.0 | 2.0 |
| Subsequent IO | 43 | 14.0 | 8.0 | 3.0 |
9 patients received other 1L Tx. CT, chemotherapy; IO, immunotherapy; Tx, treatment.
Conclusions
Robust and durable efficacy, particularly in the 1L setting, support early use of tepotinib in Tx sequence. Almost half of this elderly population received subsequent Tx, higher than the 20–30% reported for 1L CT/IO IPSOS trial in elderly pts (median age 75). METi Tx sequencing analyses ongoing.
Clinical trial identification
NCT02864992.
Editorial acknowledgement
Medical writing assistance (funded by Merck Healthcare KGaA, Darmstadt, Germany) was provided by Syneos Health, London, UK.
Legal entity responsible for the study
Merck Healthcare KGaA, Darmstadt, Germany.
Funding
Merck Healthcare KGaA, Darmstadt, Germany (CrossRef Funder ID: 10.13039/100009945).
Disclosure
F. Griesinger: Non-Financial Interests, Personal, Advisory Role: Amgen, AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Celgene, GSK, Eli Lilly, MSD, Novartis, Pfizer, Roche, Siemens, Takeda; Non-Financial Interests, Personal, Other, Honoraria: Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, BMS, Celgene, GSK, Eli Lilly, MSD, Novartis, Pfizer, Roche, Siemens, Takeda; Financial Interests, Personal, Research Grant: Amgen, AstraZeneca, Boehringer Ingelheim, BMS, Celgene, GSK, Eli Lilly, MSD, Novartis, Pfizer, Roche, Siemens, Takeda. M.C. Garassino: Non-Financial Interests, Personal, Other, Honoraria: MSD Oncology, AstraZeneca/MedImmune, GlaxoSmithKline, Takeda, Roche, Bristol Myers Squibb; Non-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, GlaxoSmithKline, Bayer Healthcare Pharmaceuticals, Blueprint Medicines, Janssen, Regeneron; Non-Financial Interests, Personal, Speaker's Bureau: AstraZeneca, Takeda, MSD Oncology, Celgene, Incyte, Roche, Bristol Myers Squibb, Otsuka, Eli Lilly; Financial Interests, Institutional, Research Grant: Bristol Myers Squibb, MSD, Roche/Genentech, AstraZeneca/MedImmune, AstraZeneca, Pfizer, GlaxoSmithKline, Novartis, Merck Healthcare KGaA, Darmstadt, Germany, Incyte, Takeda, Spectrum Pharmaceuticals, Blueprint Medicine, Eli Lilly, Ipsen, Janssen, Exelixis, MedImmune, Sanofi, Pfizer, Amgen; Financial Interests, Personal, Other, Travel, accommodation, expenses: Pfizer, Roche, AstraZeneca. E. Felip: Non-Financial Interests, Personal, Advisory Role: Pfizer, Roche, Boehringer Ingelheim, AstraZeneca, Bristol Myers Squibb, Guardant Health, Novartis, Takeda, AbbVie, Blueprint Medicines, Eli Lilly, Merck Healthcare KGaA, Darmstadt, Germany, Merck Sharp & Dohme, Janssen, Samsung; Non-Financial Interests, Personal, Speaker's Bureau, and expert testimony: Pfizer, Roche, AstraZeneca, Bristol Myers Squibb, Novartis, Takeda, Eli 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); Non-Financial Interests, Personal, Officer, Officer/Board of Directors: Grifols (Independent Member). H. Sakai: Non-Financial Interests, Personal, Speaker's Bureau: Bristol Myers Squibb, Ono Pharmaceutical, MSD K.K., AstraZeneca, Chugai Pharma, Taiho Pharmaceutical, Boehringer Ingelheim. X. Le: Non-Financial Interests, Personal, Advisory Role: AstraZeneca, Eli Lilly, EMD Serono, an affiliate of Merck KGaA, Novartis, Daiichi Sankyo, Hengrui Therapeutics; Financial Interests, Personal, Research Grant: Eli Lilly, Boehringer Ingelheim. R. Veillon: Non-Financial Interests, Personal, Advisory Role: MSD, Pfizer, Novartis; Non-Financial Interests, Personal, Speaker's Bureau: MSD, Bristol Myers Squibb, Roche; Financial Interests, Personal, Research Grant: Roche, Takeda, AbbVie, Merck Healthcare KGaA, Darmstadt, Germany, Bristol Myers Squibb. E.F. Smit: Non-Financial Interests, Institutional, Advisory Role: Eli Lilly, AstraZeneca, Boehringer Ingelheim, Roche/Genentech, Bristol Myers Squibb, Merck Healthcare KGaA, Darmstadt, Germany, MSD Oncology, Takeda, Bayer, Regeneron, Novartis, Daiichi Sankyo, Seattle Genetics; Financial Interests, Institutional, Research Grant: Boehringer Ingelheim, Roche/Genentech, AstraZeneca, Bristol Myers Squibb; Financial Interests, Personal and Institutional, Research Grant: Bayer. J. Raskin: Non-Financial Interests, Personal, Advisory Role: Pfizer, Eli Lilly; Non-Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim, Bristol Myers Squibb; Financial Interests, Personal, Other, Travel expenses: Roche. M. Thomas: Non-Financial Interests, Personal, Other, Honoraria – Scientific Meetings: AbbVie, Bristol Myers Squibb, MSD, AstraZeneca, Novartis, Roche, Takeda, Eli 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, Eli Lilly, Chugai Pharma, Celgene, Boehringer Ingelheim, Pfizer; Non-Financial Interests, Personal, Advisory Board: AbbVie, Bristol Myers Squibb, MSD, AstraZeneca, Novartis, Roche, Takeda, Eli Lilly, Chugai Pharma, Celgene, Boehringer Ingelheim, Pfizer, Janssen, Daiichi Sankyo, GSK, Merck Healthcare KGaA, Darmstadt, Germany, Sanofi, Amgen; Financial Interests, Institutional, Research Grant: Bristol Myers Squibb, AstraZeneca, Roche, Takeda. M. Ahn: Non-Financial Interests, Personal, Advisory Role: AstraZeneca, Eli Lilly, Amgen, Merck 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: Non-Financial Interests, Personal, Advisory Role: Takeda, Xencor, CrownBio, Bicara, Mirati, EMD Serono, an affiliate of Merck KGaA; Financial Interests, Institutional, Research Grant: Bicara, Boehringer Ingelheim, EMD Serono, an affiliate of Merck KGaA.