TY - JOUR
T1 - INSIGHT 2
T2 - A phase II study of tepotinib plus osimertinib in MET-Amplified NSCLC and first-line osimertinib resistance
AU - Smit, Egbert F.
AU - Dooms, Christophe
AU - Raskin, Jo
AU - Nadal, Ernest
AU - Tho, Lye M.
AU - Le, Xiuning
AU - Mazieres, Julien
AU - S Hin, How
AU - Morise, Masahire
AU - Zhu, Viola W.
AU - Tan, Daniel
AU - H Holmberg, Kristina
AU - Ellers-Lenz, Barbara
AU - Adrian, Svenja
AU - Brutlach, Sabine
AU - Schumacher, Karl M.
AU - Karachaliou, Niki
AU - Wu, Yi Long
N1 - Funding Information:
The trial was sponsored by Merck Healthcare KGaA, Darmstadt, Germany. EF Smit has a role in advisory/consultancy (institution): Lilly, AstraZeneca, Boehringer Ingelheim, Roche/Genentech, Bristol-Myers Squibb, Merck Healthcare KGaA, Darmstadt, Germany, MSD Oncology, Takeda, Bayer, Regeneron, Novartis, Daiichi Sankyo and Seattle Genetics; research funding (institution): Boehringer Ingelheim, Bayer, Roche/Genentech, AstraZeneca and Bristol-Myers Squibb. C Dooms has nothing to disclose. J Raskin has an advisory role: Pfizer and Lilly; invited speaker: Boehringer Ingelheim and Bristol-Myers Squibb; travel expenses: Roche. E Nadal received consulting fee and has advisory role: EMD Serono, an affiliate of Merck KGaA; research grants: Merck Healthcare KGaA, Darmstadt, Germany. LM Tho has received honoraria: Pfizer, Roche and AstraZeneca. X Le has a consulting or advisory role: AstraZeneca, Eli Lilly and EMD Serono, an affiliate of Merck KGaA; research funding: Eli Lilly and Boehringer Ingelheim. J Mazieres is a member of advisory boards: Roche, Bristol-Myers Squibb, MSD, AstraZeneca, Pfizer and Novartis. HS Hin has nothing to disclose. M Morise received Speakers’ bureau fees: Chugai, MSD, ONO and AstraZeneca. VW Zhu has a role in advisory/consulting role: AstraZeneca, Takeda, TP Therapeutics, Roche/Genentech and Xcovery; speaker fees: AstraZeneca, Roche/Genentech, Takeda and Blueprint Medicines; travel expenses: AstraZeneca, Roche/Genentech, Takeda and TP Therapeutics; stock: TP Therapeutics; honoraria: AstraZeneca, Roche/Genentech, Takeda, Blueprint Medicines and Xcovery. D Tan received research grant advisory and consultancy honoraria: Novartis, Pfizer and AstraZeneca; research grant and advisory/consultancy: Bayer; advisory and consultancy honoraria: Boehringer Ingelheim and Takeda; honoraria: Bristol-Myers Squibb, Takeda Pharmaceuticals, Novartis, Roche, Pfizer and Merck Healthcare KGaA, Darmstadt, Germany; consulting or advisory role: Eli-Lilly, Merrimack, Novartis, Merck Healthcare KGaA, Darmstadt, Germany, Loxo Oncology, AstraZeneca, Roche and Pfizer; institute research funding: Novartis, GlaxoSmithKline and AstraZeneca. KH Holmberg is an employee and shareholder of EMD Serono Research & Development Institute, Inc., Billerica, MA, USA, an affiliate of Merck KGaA. B Ellers-Lenz, N Karachaliou, S Adrian, S Brutlach and KM Schumacher are employees of Merck Healthcare KGaA, Darmstadt, Germany. Y-L Wu received institute grants and personal fees: AstraZeneca, Roche and Boehringer Ingelheim; personal fees (speaker): Bristol-Myers Squibb, MSD, Eli Lilly and Pfizer. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
Publisher Copyright:
© 2021 The Authors.
PY - 2022/3
Y1 - 2022/3
N2 - MET amplification (METamp), a mechanism of acquired resistance to EGFR tyrosine kinase inhibitors, occurs in up to 30% of patients with non-small-cell lung cancer (NSCLC) progressing on first-line osimertinib. Combining osimertinib with a MET inhibitor, such as tepotinib, an oral, highly selective, potent MET tyrosine kinase inhibitor, may overcome METamp-driven resistance. INSIGHT 2 (NCT03940703), an international, open-label, multicenter phase II trial, assesses tepotinib plus osimertinib in patients with advanced/metastatic EGFR-mutant NSCLC and acquired resistance to first-line osimertinib and METamp, determined centrally by fluorescence in situ hybridization (gene copy number ?5 and/or MET/CEP7 ?2) at time of progression. Patients will receive tepotinib 500 mg (450 mg active moiety) plus osimertinib 80 mg once-A-day. The primary end point is objective response, and secondary end points include duration of response, progression-free survival, overall survival and safety. Trial registration number: NCT03940703 (clinicaltrials.gov)
AB - MET amplification (METamp), a mechanism of acquired resistance to EGFR tyrosine kinase inhibitors, occurs in up to 30% of patients with non-small-cell lung cancer (NSCLC) progressing on first-line osimertinib. Combining osimertinib with a MET inhibitor, such as tepotinib, an oral, highly selective, potent MET tyrosine kinase inhibitor, may overcome METamp-driven resistance. INSIGHT 2 (NCT03940703), an international, open-label, multicenter phase II trial, assesses tepotinib plus osimertinib in patients with advanced/metastatic EGFR-mutant NSCLC and acquired resistance to first-line osimertinib and METamp, determined centrally by fluorescence in situ hybridization (gene copy number ?5 and/or MET/CEP7 ?2) at time of progression. Patients will receive tepotinib 500 mg (450 mg active moiety) plus osimertinib 80 mg once-A-day. The primary end point is objective response, and secondary end points include duration of response, progression-free survival, overall survival and safety. Trial registration number: NCT03940703 (clinicaltrials.gov)
KW - EGFR tyrosine kinase inhibitors
KW - MET amplification
KW - non-small-cell lung cancer
KW - osimertinib
KW - tepotinib
UR - http://www.scopus.com/inward/record.url?scp=85125966322&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85125966322&partnerID=8YFLogxK
U2 - 10.2217/fon-2021-1406
DO - 10.2217/fon-2021-1406
M3 - Article
C2 - 34918545
AN - SCOPUS:85125966322
SN - 1479-6694
VL - 18
SP - 1039
EP - 1054
JO - Future Oncology
JF - Future Oncology
IS - 9
ER -