566P - Safety of tepotinib + osimertinib in EGFR-mutant NSCLC with MET amplification after first-line osimertinib

Background

Promising clinical activity has been reported in the INSIGHT 2 (NCT03940703) study of tepotinib (TEP) + osimertinib (OSI) in patients with EGFR-mutant (m) NSCLC with MET amplification (METamp) progressing on first-line OSI, with an objective response rate (ORR) of 50.0% (95% CI: 39.7, 60.3) and median duration of response (mDOR) of 8.5 months (95% CI: 6.1, not estimable [ne]). In patients enrolled in Asia, ORR was 59.6% (95% CI: 45.1, 73.0) and mDOR was 7.3 months (95% CI: 4.7, ne). Given the high incidence of EGFRm NSCLC in Asia, we report comprehensive safety data for patients enrolled in Asia to inform patient care and management.

Methods

TEP 500 mg (450 mg active moiety) was administered in combination with OSI 80 mg QD until disease progression, intolerable toxicity, or withdrawal. To manage AEs, drugs could be dose reduced or discontinued as needed. AE severity was graded by NCI-CTCAE v5.0. Data cut-off: March 28, 2023.

Results

Of 128 patients receiving TEP+OSI, 76 (59.4%) were enrolled in Asia. Of patients in Asia, treatment-related AEs (TRAEs) of any grade occurred in 67 patients (88.2%), and Grade ≥3 TRAEs occurring in 26 patients (34.2%). The most common TRAEs were diarrhea in 34 patients (44.7%; all Grade 1 or 2) and peripheral edema in 30 patients (39.5%; including 3.9% Grade ≥3) (Table). TRAEs led to a dose reduction of TEP and/or OSI in 14 patients (18.4%). The most common TRAEs leading to dose reduction were peripheral edema and decreased appetite (n=3 each). TRAEs led to permanent discontinuation in six patients (7.9%), with pneumonitis being the most common TRAE leading to discontinuation (n=3). TRAEs that led to death occurred in three patients: one patient had platelet count decrease (disease progression), one patient had pneumonitis, and one patient had respiratory failure (COVID-19). Table: 566P

ALT, alanine aminotransferase; AST, aspartate aminotransferase; TRAE, treatment-related adverse event.

Conclusions

TEP+OSI was generally well tolerated in patients in Asia, comparable to the overall population. Most AEs were considered manageable with TEP and/or OSI dose modifications.

Clinical trial identification

NCT03940703.

Editorial acknowledgement

Medical writing assistance (funded by Merck) was provided by Vivian Anastasiou, PhD on behalf of Syneos Health, London, UK.

Legal entity responsible for the study

Merck Healthcare KGaA, Darmstadt, Germany.

Funding

Merck.

Disclosure

C.K. Liam: Financial Interests, Personal, Research Grant: AstraZeneca, Boehringer Ingelheim ; Financial Interests, Personal, Other, Honoraria and fees for lectures and advisory board meetings: AstraZeneca, Boehringer Ingelheim, Eli Lilly, MSD, Novartis, Pfizer, Roche, Zuelig Pharma, Bristol Myer Squibbb, Merck, Janssen. T.M. Kim: Financial Interests, Personal, Advisory Role: AstraZeneca, Boryung, Hanmi, IMBDx.Inc, Janssen, Novartis, Takeda, Sanofi, Regeneron, Roche/Genentech, Samsung Bioepis. P. Voon: Financial Interests, Personal, Advisory Role: AstraZeneca, Ipsen, MSD, Novartis, Pfizer; Financial Interests, Personal, Research Funding: AstraZeneca, Novartis, Boehringer Ingelheim, Janssen-Cilag, Johnson & Johnson, Viracta Therapeutics Inc, Roche, Merck, MSD. L.M. Tho: Financial Interests, Personal, Advisory Board, Advisory Board & Speaker honoraria: Pfizer, Roche, AstraZeneca, Boehringer Ingelheim, Novartis, Merck. H. Hayashi: Financial Interests, Personal, Other, Honoraria: Ono Pharmaceutical, Bristol Myers Squibb Japan, Lilly, Boehringer Ingelheim, Chugai Pharma, Pfizer, MSD, Novartis, Merck, Amgen, Daiichi Sankyo/ UCB Japan, Guardant Health, Takeda; Financial Interests, Personal, Advisory Role: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo/UCB Japan, Janssen; Financial Interests, Personal, Research Funding: Ono Pharmaceutical, Boehringer Ingelheim, AstraZeneca, AbbVie, AC Medical, Astellas Pharma, Bristol Myers Squibb, Daiichi Sankyo, Eisai, Lilly Japan, EPS Associates Co., Ltd., GSK, Japan Clinical Research Operations, Kyowa Hakko Kirin, Merck, Novartis, Otsuka, PAREXEL, Pfizer, PPD-SNBL, Quintiles Inc., Taiho Pharmaceutical, Takeda, Yakult Honsha, Chugai Pharma, Sysmex; Financial Interests, Personal, Other, Patents, Royalties, other intellectual Property: Sysmex. D.S.W. Tan: Financial Interests, Personal, Advisory Role: Novartis, Merck, Loxo, AstraZeneca, Roche, Pfizer, C4 Therapeutics; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Pfizer, Boehringer Ingelheim, Roche; Financial Interests, Personal, Other, Honoraria: Bristol Myers Squibb, Takeda, Novartis, Roche, Pfizer; Financial Interests, Personal, Research Funding: Novartis, GSK, AstraZeneca. P. Danchaivijitr: Financial Interests, Personal, Advisory Role: AstraZeneca, Roche, MSD; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: MSD; Financial Interests, Personal, Other, Honoraria: MSD, AstraZeneca, Roche; Financial Interests, Personal, Research Funding: Research University Network. J.C. Yang: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Daiichi Sankyo, MSD, Novartis, Roche/Genentech, Takeda Oncology, Yuhan Pharmaceuticals, Ono Pharmaceuticals, Pfizer, AstraZeneca ; Financial Interests, Personal, Research Funding: Eli Lily, JNJ, Puma Technology, Gilead, GSK, Amgen, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, MSD, Novartis, Roche/Genentech, Takeda Oncology, Yuhan Pharmaceuticals. X. Le: Financial Interests, Personal, Advisory Role: AstraZeneca, Lilly, EMD Serono Research & Development Institute, Inc., Billerica, MA, USA, an affiliate of Merck KGaA, Spectrum Pharmaceuticals, Daiichi Sankyo/Lilly, Novartis, Hengrui Therapeutics, Janssen Oncology, Blueprint Medicines, Sensei Biotherapeutics, AbbVie, Arrivent; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Spectrum Pharmaceuticals, EMD Serono Research & Development Institute, Inc., Billerica, MA, USA, an affiliate of Merck KGaA; Financial Interests, Personal, Research Funding: Lilly, Boehringer Ingelheim, Arrivent, Teligene. B. Ellers-Lenz, N. Karachaliou, V. Ghori, K. Berghoff: Financial Interests, Personal, Full or part-time Employment: Merck. Y. Wu: Financial Interests, Personal, Other, Institute grants and personal fees: AstraZeneca, Roche, Boehringer Ingelheim; Financial Interests, Personal, Speaker, Consultant, Advisor: BMS, MSD, Eli Lilly, Pfizer. All other authors have declared no conflicts of interest.