@article{9a7c46e1dc3949369158b57cd7a82f04,
title = "Activity and safety of mobocertinib (Tak-788) in previously treated non–small cell lung cancer with egfr exon 20 insertion mutations from a phase i/ii trial",
abstract = "Mobocertinib, an oral epidermal growth factor receptor (EGFR) inhibitor targeting EGFR gene mutations, including exon 20 insertions (EGFRex20ins), in non– small cell lung cancer, was evaluated in a phase I/II dose-escalation/expansion trial (ClinicalTrials. gov NCT02716116). Dose escalation identified 160 mg/d as the recommended phase 2 dose and maximum tolerated dose. Among 136 patients treated with 160 mg/d, the most common any-grade treatment-related adverse events (TRAE; >25%) were diarrhea (83%), nausea (43%), rash (33%), and vomiting (26%), with diarrhea (21%) the only grade ≥3 TRAE >5%. Among 28 EGFRex20ins patients treated at 160 mg/d, the investigator-assessed confirmed response rate was 43% (12/28; 95% con-fidence interval, 24%–63%) with median duration of response of 14 months (5.0–not reached) and median progression-free survival of 7.3 months (4.4–15.6). Mobocertinib demonstrated antitumor activity in patients with diverse EGFRex20ins variants with a safety profile consistent with other EGFR inhibitors. Significance: No oral EGFR-targeted therapies are currently approved for patients with EGFRex-20ins NSCLC. Mobocertinib demonstrated antitumor activity with manageable toxicity in patients with advanced EGFRex20ins NSCLC in this study, supporting additional development of mobocertinib in this patient population.",
author = "Riely, {Gregory J.} and Neal, {Joel W.} and Camidge, {D. Ross} and Spira, {Alexander I.} and Zofia Piotrowska and Costa, {Daniel B.} and Tsao, {Anne S.} and Patel, {Jyoti D.} and Gadgeel, {Shirish M.} and Lyudmila Bazhenova and Zhu, {Viola W.} and West, {Howard L.} and Tarek Mekhail and Gentzler, {Ryan D.} and Danny Nguyen and Sylvie Vincent and Steven Zhang and Jianchang Lin and Veronica Bunn and Shu Jin and Shuanglian Li and J{\"a}nne, {Pasi A.}",
note = "Funding Information: G.J. Riely reports institutional research funding from Takeda/ Millennium/ARIAD, Pfizer, Novartis, Roche/Genentech, GSK, Infinity Pharmaceuticals, Merck, and Mirati; and travel reimbursement from Merck. J.W. Neal reports having a consultant/advisory role with AstraZeneca, Genentech/Roche, Exelixis, Jounce Therapeutics, Takeda, Eli Lilly, Calithera Biosciences, Regeneron Pharmaceuticals, Amgen [DSMB], Iovance Biotherapeutics [DSMB], Blueprint Pharmaceuticals; receiving honoraria from Research to Practice, MLI Peerview, Medscape, Biomedical Learning Institute, Prime Oncology, Rockpointe, CME Matters, MJH CME; and institutional research funding from Genentech/Roche, Merck, Novartis, Boehringer Ingel-heim, Exelixis, Nektar, Takeda, Adaptimmune, GSK. D.R. Camidge reports receiving honoraria from AstraZeneca, Takeda, Arrys/Kyn, Genoptix, G1 Therapeutics [DSMB], Mersana Therapeutics, Roche/ Genentech, Ignyta, Daiichi Sankyo [ILD adjudication committee], Hansoh SRC, Bio-Thera DSMB, Lycera, Revolution Med, Orion, Clovis, Celgene, Novartis; and research funding from ARIAD/Takeda. A.I. Spira reports having a consultant/advisory role with ARIAD, Astellas, AstraZeneca, BMS, Clovis Oncology, Janssen, Merck, Roche; receiving research support from AstraZeneca, Millennium, Merck, Janssen, Roche, Novartis, Cullinan Pearl, Daichi Sankyo; and serving as a speaker for Roche. Z. Piotrowska reports having a consultant/ advisory role with AstraZeneca, ARIAD/Takeda, AbbVie, Novartis, Guardant Health, Spectrum, Genetech, ImmunoGen, C4 Therapeutics, Blueprint Medicines, Jazz Pharmaceutics, Janssen; receiving research support from Novartis, ARIAD/Takeda, GuardantHealth, Spectrum, AstraZeneca, Tesaro, and Cullinan; and travel reimbursement from AstraZeneca, ARIAD/Takeda. D.B. Costa reports personal fees (consulting fees and honoraria) and nonfinancial support (institutional research support) from Takeda/Millennium Pharma- ceuticals, AstraZeneca, and Pfizer, as well as nonfinancial support (institutional research support) from Merck Sharp and Dohme Corporation, Merrimack Pharmaceuticals, Bristol-Myers Squibb, Clovis Oncology, Spectrum Pharmaceuticals, Blueprint Medicines, Genen-tech, and Tesaro, all outside the submitted work. A.S. Tsao reports having a consultant/advisory role with Novartis, Boehringer Ingel-heim, Genentech/Roche, MedImmune, Imedex, Lilly, BMS, Epizyme, AstraZeneca/MedImmune, ARIAD, EMD Serono, Takeda, HERON; receiving royalties from UptoDate; research funding from Seattle Genetics, Millennium, Polaris, BMS, (following to institution) Med-Immune, Merck, Genentech/Roche, BMS, Boehringer Ingelheim. J.D. Patel reports having an advisory role with AbbVie, AstraZeneca, Takeda. S.M. Gadgeel reports having a consultant/advisory role with Pfizer, Genentech/Roche, ARIAD, AstraZeneca, BMS, AbbVie; being a member of a speakers bureau for AstraZeneca; receiving travel/ accommodations/expenses from ARIAD/Takeda, Genentech/Roche; and research funding from Merck, (following to institution) Pfizer, Genentech/Roche, Merck, Blueprint Medicines, ARIAD/Takeda. L. Bazhenova reports having an advisory role with Genentech, Novartis, Regeneron, BI, BMS, Johnson and Johnson, Merck; receiving research funding from BeyondSpring Pharmaceuticals; and being a shareholder in Epic Sciences. V.W. Zhu reports receiving honoraria from AstraZeneca, Roche-Foundation Medicine, Roche/Genentech, Takeda; having a consultant/advisory role with TP Therapeutics; owning stock or other ownership options with TP Therapeutics; and being a member of a speakers bureau for AstraZeneca, Roche-Foundation Medicine, Roche/Genentech, Takeda. H.L. West reports receiving personal fees as an advisory board member, consultant, and speaker from Genentech/Roche, Takeda/ARIAD, and as a consultant and speaker from Novartis, Pfizer. T. Mekhail has no disclosures to report. R.D. Gentzler reports receiving honoraria from Rockpointe CME; consulting fees from AstraZeneca, Pfizer, Blueprint Medicines, ARIAD; and research funding to institution from Merck, Bristol-Myers Squibb, Takeda, Jounce Therapeutics, Helsinn, and Pfizer. D. Nguyen has no disclosures to report. S. Vincent reports employment with Takeda. S. Zhang reports employment with Takeda. J. Lin reports employment with Takeda. V. Bunn reports employment with Takeda. S. Jin reports employment with Takeda. S. Li reports former employment with Takeda. P.A. J{\"a}nne reports grants and personal fees from Takeda Oncology during the conduct of the study; grants from AstraZeneca, Boehringer Ingelheim, Eli Lilly and Company, PUMA, Astellas Pharmaceuticals, and Daiichi Sankyo; and personal fees from Araxes Pharmaceuticals, ARIAD/Takeda; AstraZeneca, AbbVie, Mirati Therapeutics, Boehringer Ingelheim, Pfizer, Roche/Genentech, Chugai Pharmaceuticals, Eli Lilly and Company, Ignyta, Merrimack, Novartis, Voronoi, SFJ Pharmaceuticals, Biocartis, LOXO Oncology, PUMA, Sanofi, Transcenta, Daiichi Sankyo, and Silicon Therapeutics, outside the submitted work; and is a shareholder of Gatekeeper and LOXO Oncology. In addition, Dr. J{\"a}nne receives postmarketing royalties from a DFCI-owned patent on EGFR mutations licensed to Lab Corp. Funding Information: We thank the patients, their families, and their caregivers; the investigators and their team members at each study site; and colleagues from Millennium Pharmaceuticals, Inc., Cambridge, MA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited. Professional medical writing assistance was provided by Lauren Gallagher, RPh, PhD, and Lela Creutz, PhD, of Peloton Advantage, LLC, an OPEN Health company, Parsippany, NJ, and funded by Millennium Pharmaceuticals, Inc. Teodor G. Paunescu, PhD (Millennium Pharmaceuticals, Inc., Cambridge, MA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited) is acknowledged for editorial assistance. This work was funded in part through a National Institutes of Health/National Cancer Institute (NCI) grant (R37CA218707) to D.B. Costa for case preselection and genomic analyses at Beth Israel Deaconess Medical Center, a member of the NCI-designated Dana-Farber/Harvard Cancer Center. Publisher Copyright: {\textcopyright} 2021 American Association for Cancer Research.",
year = "2021",
month = jul,
doi = "10.1158/2159-8290.CD-20-1598",
language = "English (US)",
volume = "11",
pages = "1688--1699",
journal = "Cancer Discovery",
issn = "2159-8274",
publisher = "American Association for Cancer Research Inc.",
number = "7",
}
