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

Gregory J. Riely, Joel W. Neal, D. Ross Camidge, Alexander I. Spira, Zofia Piotrowska, Daniel B. Costa, Anne S. Tsao, Jyoti D. Patel, Shirish M. Gadgeel, Lyudmila Bazhenova, Viola W. Zhu, Howard L. West, Tarek Mekhail, Ryan D. Gentzler, Danny Nguyen, Sylvie Vincent, Steven Zhang, Jianchang Lin, Veronica Bunn, Shu JinShuanglian Li, Pasi A. Jänne

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)1688-1699
Number of pages12
JournalCancer discovery
Volume11
Issue number7
DOIs
StatePublished - Jul 2021
Externally publishedYes

ASJC Scopus subject areas

  • Oncology

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