1358P - Safety of tepotinib + EGFR TKI (osimertinib or gefitinib) in patients with EGFRm NSCLC

Background

Promising clinical activity has been reported in the INSIGHT 2 study of tepotinib (TEP) + osimertinib (OSI) in patients (pts) with EGFRm NSCLC with MET amplification (METamp) progressing on OSI, with an ORR of 43.9% (95% CI: 33.9, 54.3) and a mDOR of 9.7 months (5.6, ne). TEP monotherapy has been extensively studied in METex14 skipping NSCLC (N=313) and is generally well tolerated, with low discontinuation rates due to treatment-related AEs (TRAEs; 14.7%). The most common TRAE is peripheral edema (67.1%, Grade 3 11.2%). Our aim is to further characterize the safety profile of TEP in combination with EGFR TKIs.

Methods

TEP 500 mg (450 mg active moiety) was administered in combination with OSI 80 mg (INSIGHT 2; NCT03940703) or gefitinib (GEF) 250 mg (INSIGHT; NCT01982955) QD until disease progression, intolerable toxicity, or withdrawal. To manage AEs, each drug could be dose reduced but if discontinuation was needed, both drugs were stopped. AEs were graded by NCI-CTCAE v5.0.

Results

As of Sep 26, 2022, 187 pts with EGFRm NSCLC (65% <65 yrs, 62% female, 72% Asian, 70% nonsmokers, 75% ECOG PS 1) had received TEP + EGFR TKI: 129 +OSI and 58 +GEF. TRAEs were mostly Grade 1–2 and included diarrhea, peripheral edema, and paronychia (Table). TRAEs leading to dose reduction of TEP (≥3 pts) were decreased appetite, peripheral edema, and nausea. There were few discontinuations due to TRAEs (≥2 pts: peripheral edema and pneumonitis). Two deaths considered to be treatment related (due to pneumonitis and dyspnea) occurred in pts receiving TEP+OSI.

Conclusions

TEP in combination with an EGFR TKI was well tolerated in these pts with progressive disease post-first-line therapy, and reflects the safety profile of the individual compounds. Lower incidence of peripheral edema in pts with EGFRm NSCLC versus METex14 skipping NSCLC may be due to younger age and/or the EGFR TKI combination. TEP+OSI provides a potential chemotherapy-sparing oral targeted therapy option for patients with EGFRm METamp NSCLC that has developed resistance. Table: 1358P

*Related to TEP and/or EGFR TKI (OSI/GEF).

Clinical trial identification

NCT03940703 and NCT01982955.

Editorial acknowledgement

Medical writing assistance (funded by Merck Healthcare KGaA, Darmstadt, Germany) 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 Healthcare KGaA, Darmstadt, Germany (CrossRef Funder ID: 10.13039/100009945).

Disclosure

E. Nadal: Financial Interests, Personal, Advisory Role: Bristol Myers Squibb, Merck Sharp & Dohme, Roche, Amgen, Pfizer, Eli Lilly and Company, Takeda, Sanofi, Bayer, AstraZeneca, Merck Healthcare KGaA, Darmstadt, Germany; Financial Interests, Personal, Other, Honoraria: Bristol Myers Squibb, Merck Sharp & Dohme, Roche, Amgen, Pfizer, Eli Lilly and Company, Takeda, Bayer, AstraZeneca, Boehringer Ingelheim; Financial Interests, Personal, Research Funding: Bristol Myers Squibb, Merck Healthcare KGaA, Darmstadt, Germany, Roche, Pfizer. T.M. Kim: Financial Interests, Personal, Advisory Role: AstraZeneca, Boryung, Hanmi, Novartis, Takeda, Sanofi, Regeneron, Roche/Genetech, Janssen, IMBDx. Inc, Samsung Bioepis; Financial Interests, Personal, Research Grant, received outside this work: AstraZeneca-KHIDI. V. Guarneri: Financial Interests, Personal, Advisory Role: Lilly, Novartis, MSD, Gilead , Eisai , Merck Healthcare KGaA, Darmstadt, Germany, Olema Oncology, Exact Sciences; Financial Interests, Personal, Speaker’s Bureau: Novartis, Lilly, GSK, Amgen, AstraZeneca; Financial Interests, Personal, Research Funding: AstraZeneca, Roche, Novartis, BMS, Lilly, Merck Healthcare KGaA, Darmstadt, Germany, Daiichi Sankyo/AstraZeneca, Nerviano Medical Sciences, GSK, Synton Biopharmaceuticals; Financial Interests, Personal, Expert Testimony: Lilly; Financial Interests, Personal, Other, Travel, Accommodations and Expenses: Gilead/Entry Seven. P.J. Voon: Financial Interests, Personal, Advisory Role: AstraZeneca, Ipsen, MSD, Novartis, Pfizer; Financial Interests, Personal, Research Funding: Boehringer Ingelheim, Janssen-Cilag, Johnson & Johnson, Viracta Therapeutics Inc., Roche, Merck Healthcare KGaA, Darmstadt, Germany, MSD, AstraZeneca, Novartis. M. Wislez: Financial Interests, Personal, Advisory Board: Roche, BMS, MSD, AstraZeneca, Pfizer, Novartis, Merck Healthcare KGaA, Darmstadt, Germany, Janssen. C.K. Liam: Financial Interests, Personal, Other, Honoraria and fees for lectures and advisory board meetings: Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, MSD, Novartis, Pfizer, Roche, Zueling Pharma. J. Mazieres: Financial Interests, Personal, Advisory Board: Roche, BMS, MSD, AstraZeneca, Pfizer, Novartis, Merck Healthcare KGaA, Darmstadt, Germany, Amgen, Takeda, Daiichi Sankyo; Financial Interests, Institutional, Research Funding: Roche/Genentech, AstraZeneca, Brystol Myers Squibb. L.M. Tho: Financial Interests, Personal, Advisory Board: Pfizer, Roche, AstraZeneca, Boehringer Ingelheim, Novartis, Merck Healthcare KGaA, Darmstadt, Germany; Financial Interests, Personal, Other, Speaker Honoraria: Pfizer, Roche, AstraZeneca, Boehringer Ingelheim, Novartis, Merck Healthcare KGaA, Darmstadt, Germany. H. Hayashi: Financial Interests, Personal, Other, Honoraria: Ono Pharmaceutical, Bristol Myers Squibb Japan, Lilly, Boehringer Ingelheim, Chugai Pharma, Pfizer, MSD, Novartis, Merck Healthcare KGaA, Darmstadt, Germany, 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 Healthcare KGaA, Darmstadt, Germany, 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. P.L. Chia: Financial Interests, Personal, Advisory Board: AstraZeneca, MSD, Amgen, Pfizer, Bayer; Financial Interests, Personal, Other, Honoraria for symposium: AstraZeneca, Lung Cancer Consortium Singapore; Financial Interests, Institutional, Research Funding: AstraZeneca; Financial Interests, Personal, Other, Travel Expenses: IASCLC for WCLC 2022 . F. de Marinis: Financial Interests, Personal, Advisory Board: AstraZeneca, Bristol Myers Squibb, Novartis, F. Hoffmann La-Roche Ltd., MSD. S. Brutlach, S. Adrian, B. Ellers-Lenz, K. Berghoff, N. Karachaliou, Financial Interests, Personal, Full or part-time Employment: Merck Healthcare KGaA, Darmstadt, Germany. Y. Wu: Financial Interests, Personal and Institutional, Other, Institute grants and personal fees: AstraZeneca, Roche, Boehringer Ingelheim; Financial Interests, Personal, Invited Speaker: BMS, MSD, Eli Lilly, Pfizer. All other authors have declared no conflicts of interest.