364P - Tepotinib with an EGFR-tyrosine kinase inhibitor (TKI) in patients with EGFR-mutant MET-amplified NSCLC: A case series

Background

MET amplification (METamp) is a mechanism of acquired resistance to EGFR-TKIs. In the INSIGHT trial (NCT01982955), in patients with EGFR-mutant METamp NSCLC and EGFR-TKI resistance, tepotinib (a potent, highly selective MET-TKI) plus gefitinib (EGFR-TKI) improved outcomes in comparison with chemotherapy. We present a case series highlighting the clinical activity of tepotinib plus an EGFR-TKI (gefitinib and/or osimertinib) in patients with EGFR-mutant METamp NSCLC.

Methods

Early access to tepotinib has been provided through compassionate use. Cases include patients with NSCLC and acquired resistance to EGFR-TKIs due to METamp who received tepotinib outside of a clinical trial (500 mg [450 mg active moiety] once daily; first dose before Oct 2021) plus an EGFR-TKI.

Results

Twelve cases of patients with EGFR-mutant METamp NSCLC who received tepotinib plus an EGFR-TKI are presented (five received second-line treatment, three third-line, and four fourth-or-later line). Patients were aged 47–86 years, five were Asian, eight were female, three had smoking history, and all had adenocarcinoma histology. METamp was detected in 10 patients by tissue biopsy and two patients by liquid biopsy. Of seven patients with METamp detected by FISH, MET gene copy number ranged from 5.5–33.4, and MET:CEP7 ratio from 1.8–15.1. Nine patients received tepotinib plus osimertinib, two received tepotinib plus gefitinib, and one received both combinations sequentially. The treatment duration ranged from 1.3–13.8 months. At the time of data collection, treatment was ongoing in four patients. Per the treating physician’s assessment, 11 patients had clinical benefit, eight of whom were considered to have a partial response. The most common adverse event considered related to tepotinib was peripheral edema, which was reported in seven patients. Three patients had Grade 3 adverse events: one with peripheral edema and dermatitis, one with elevated amylase and lipase, and one with pneumonia and pneumonitis.

Conclusions

The combination of tepotinib plus EGFR-TKIs showed promising clinical activity in patients with METamp NSCLC who have progressed on previous EGFR-TKIs, including those with several lines of prior treatment.

Clinical trial identification

Editorial acknowledgement

Medical writing assistance (funded by Merck Healthcare KGaA, Darmstadt, Germany) was provided by Bhartendu K Srivastava 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

A.R. Ahmad: Financial Interests, Personal, Advisory Board: Boehringer Ingelheim, Novartis, Pfizer, MSD, Roche, Eisai, Viatris, Merck Healthcare KGaA, Darmstadt, Germany; Financial Interests, Personal, Speaker’s Bureau: Novartis, Pfizer, Roche, Eisai, MSD, BMS, Amgen, Duopharma, OEP, SciGen. L.M. Tho: Financial Interests, Personal, Research Grant: EMD Serono, an affiliate of Merck KGaA, Darmstadt, Germany; Financial Interests, Personal, Advisory Role: Pfizer, Roche, AstraZeneca. W.C.K. Lee: Financial Interests, Personal, Advisory Board: AstraZeneca, Janssen; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca; Financial Interests, Personal, Full or part-time Employment: ACT Genomics Ltd. X. Le: Financial Interests, Personal, Advisory Role: AstraZeneca, Eli Lilly, Novartis, Daiichi Sankyo, Hengrui Therapeutics, EMD Serono, an affiliate of Merck KGaA; Financial Interests, Personal, Research Grant: Eli Lilly, Boehringer Ingelheim. A.K. Eisert: Financial Interests, Personal, Advisory Role: Merck Healthcare KGaA, Darmstadt, Germany, Amgen. C. De Bondt: Financial Interests, Personal, Advisory Board: Janssen. J. Mazieres: Financial Interests, Personal, Advisory Board: Roche, Bristol Myers Squibb, MSD, AstraZeneca, Pfizer, Novartis, Amgen, Takeda, Daiichi Sankyo, Merck Healthcare KGaA, Darmstadt, Germany; Financial Interests, Personal, Research Grant: Roche/Genentech, AstraZeneca, Bristol Myers Squibb. I. Petrini: Financial Interests, Personal, Advisory Role: Sanofi Aventis, MSD, Takeda, Amgen, Boehringer Ingelheim. W. Lam: Financial Interests, Personal, Advisory Role: BMS, MSD, Roche, Pfizer, Novartis, AstraZeneca. K. Joshi: Financial Interests, Personal, Full or part-time Employment, Employee of ICON plc, contracted on behalf of Merck Healthcare KGaA, Darmstadt, Germany: ICON plc. K. Berghoff: Financial Interests, Personal, Full or part-time Employment, Employee of Merck Healthcare KGaA, Darmstadt, Germany: Merck Healthcare KGaA, Darmstadt, Germany. S. Vlassak: Financial Interests, Personal, Full or part-time Employment, Employee of Merck N.V-S.A., Overijse, Belgium, an affiliate of Merck KGaA, Darmstadt, Germany: Merck Healthcare KGaA, Darmstadt, Germany. N. Karachaliou: Financial Interests, Personal, Full or part-time Employment, Employee of Merck Healthcare KGaA, Darmstadt, Germany: Merck Healthcare KGaA, Darmstadt, Germany. A.J. Van Der Wekken: Financial Interests, Personal, Advisory Role: AstraZeneca, Boehringer Ingelheim, Janssen, Lilly, Novartis, Roche, Pfizer, Takeda, Merck Healthcare KGaA, Darmstadt, Germany; Financial Interests, Personal, Research Grant: AstraZeneca, Boehringer Ingelheim, Roche, Pfizer, Takeda. All other authors have declared no conflicts of interest.