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 Jin; Shuanglian Li; Pasi A. Jänne

doi:10.1158/2159-8290.CD-20-1598

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

^*Corresponding author for this work

Medicine, Hematology Oncology Division

Research output: Contribution to journal › Article › peer-review

177 Scopus citations

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 language	English (US)
Pages (from-to)	1688-1699
Number of pages	12
Journal	Cancer discovery
Volume	11
Issue number	7
DOIs	https://doi.org/10.1158/2159-8290.CD-20-1598
State	Published - Jul 2021

Funding

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.

ASJC Scopus subject areas

Oncology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1158/2159-8290.CD-20-1598

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Riely, G. J., Neal, J. W., Camidge, D. R., Spira, A. I., Piotrowska, Z., Costa, D. B., Tsao, A. S., Patel, J. D., Gadgeel, S. M., Bazhenova, L., Zhu, V. W., West, H. L., Mekhail, T., Gentzler, R. D., Nguyen, D., Vincent, S., Zhang, S., Lin, J., Bunn, V., ... Jänne, P. A. (2021). 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. Cancer discovery, 11(7), 1688-1699. https://doi.org/10.1158/2159-8290.CD-20-1598

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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 = "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",

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Riely, GJ, Neal, JW, Camidge, DR, Spira, AI, Piotrowska, Z, Costa, DB, Tsao, AS, Patel, JD, Gadgeel, SM, Bazhenova, L, Zhu, VW, West, HL, Mekhail, T, Gentzler, RD, Nguyen, D, Vincent, S, Zhang, S, Lin, J, Bunn, V, Jin, S, Li, S & Jänne, PA 2021, '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', Cancer discovery, vol. 11, no. 7, pp. 1688-1699. https://doi.org/10.1158/2159-8290.CD-20-1598

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AU - Riely, Gregory J.

AU - Neal, Joel W.

AU - Camidge, D. Ross

AU - Spira, Alexander I.

AU - Piotrowska, Zofia

AU - Costa, Daniel B.

AU - Tsao, Anne S.

AU - Patel, Jyoti D.

AU - Gadgeel, Shirish M.

AU - Bazhenova, Lyudmila

AU - Zhu, Viola W.

AU - West, Howard L.

AU - Mekhail, Tarek

AU - Gentzler, Ryan D.

AU - Nguyen, Danny

AU - Vincent, Sylvie

AU - Zhang, Steven

AU - Lin, Jianchang

AU - Bunn, Veronica

AU - Jin, Shu

AU - Li, Shuanglian

AU - Jänne, Pasi A.

PY - 2021/7

Y1 - 2021/7

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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

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UN SDGs

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