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Treatment Outcomes and Safety of Mobocertinib in Platinum-Pretreated Patients With EGFR Exon 20 Insertion–Positive Metastatic Non–Small Cell Lung Cancer: A Phase 1/2 Open-label Nonrandomized Clinical Trial

IMPORTANCE: Metastatic non–small cell lung cancer (mNSCLC) with EGFR exon 20 insertion (EGFRex20ins) mutations is associated with a poor prognosis. Mobocertinib is an oral tyrosine kinase inhibitor designed to selectively target EGFRex20ins mutations. OBJECTIVE: To evaluate treatment outcomes and sa...

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Autores principales: Zhou, Caicun, Ramalingam, Suresh S., Kim, Tae Min, Kim, Sang-We, Yang, James Chih-Hsin, Riely, Gregory J., Mekhail, Tarek, Nguyen, Danny, Garcia Campelo, Maria R., Felip, Enriqueta, Vincent, Sylvie, Jin, Shu, Griffin, Celina, Bunn, Veronica, Lin, Jianchang, Lin, Huamao M., Mehta, Minal, Jänne, Pasi A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Medical Association 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8517885/
https://www.ncbi.nlm.nih.gov/pubmed/34647988
http://dx.doi.org/10.1001/jamaoncol.2021.4761
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author Zhou, Caicun
Ramalingam, Suresh S.
Kim, Tae Min
Kim, Sang-We
Yang, James Chih-Hsin
Riely, Gregory J.
Mekhail, Tarek
Nguyen, Danny
Garcia Campelo, Maria R.
Felip, Enriqueta
Vincent, Sylvie
Jin, Shu
Griffin, Celina
Bunn, Veronica
Lin, Jianchang
Lin, Huamao M.
Mehta, Minal
Jänne, Pasi A.
author_facet Zhou, Caicun
Ramalingam, Suresh S.
Kim, Tae Min
Kim, Sang-We
Yang, James Chih-Hsin
Riely, Gregory J.
Mekhail, Tarek
Nguyen, Danny
Garcia Campelo, Maria R.
Felip, Enriqueta
Vincent, Sylvie
Jin, Shu
Griffin, Celina
Bunn, Veronica
Lin, Jianchang
Lin, Huamao M.
Mehta, Minal
Jänne, Pasi A.
author_sort Zhou, Caicun
collection PubMed
description IMPORTANCE: Metastatic non–small cell lung cancer (mNSCLC) with EGFR exon 20 insertion (EGFRex20ins) mutations is associated with a poor prognosis. Mobocertinib is an oral tyrosine kinase inhibitor designed to selectively target EGFRex20ins mutations. OBJECTIVE: To evaluate treatment outcomes and safety of mobocertinib in patients with previously treated EGFRex20ins-positive mNSCLC. DESIGN, SETTING, AND PARTICIPANTS: This 3-part, open-label, phase 1/2 nonrandomized clinical trial with dose-escalation/dose-expansion cohorts (28 sites in the US) and a single-arm extension cohort (EXCLAIM; 40 sites in Asia, Europe, and North America) was conducted between June 2016 and November 2020 (data cutoff date). The primary analysis populations were the platinum-pretreated patients (PPP) cohort and the EXCLAIM cohort. The PPP cohort included 114 patients with platinum-pretreated EGFRex20ins-positive mNSCLC who received mobocertinib 160 mg once daily from the dose-escalation (n = 6), dose-expansion (n = 22), and EXCLAIM (n = 86) cohorts. The EXCLAIM cohort included 96 patients with previously treated EGFRex20ins-positive mNSCLC (10 were not platinum pretreated and thus were excluded from the PPP cohort). INTERVENTIONS: Mobocertinib 160 mg once daily. MAIN OUTCOMES AND MEASURES: The primary end point of the PPP and EXCLAIM cohorts was confirmed objective response rate (ORR) assessed by independent review committee (IRC). Secondary end points included confirmed ORR by investigator, duration of response, progression-free survival, overall survival, and safety. RESULTS: Among the PPP (n = 114) and EXCLAIM (n = 96) cohorts, the median (range) age was 60 (27-84) and 59 (27-80) years, respectively; most patients were women (75 [66%] and 62 [65%], respectively) and of Asian race (68 [60%] and 66 [69%], respectively). At data cutoff, median follow-up was 14.2 months in the PPP cohort (median 2 prior anticancer regimens; 40 [35%] had baseline brain metastases), with confirmed ORR of 28% (95% CI, 20%-37%) by IRC assessment and 35% (95% CI, 26%-45%) by investigator assessment; median duration of response by IRC assessment was 17.5 months (95% CI, 7.4-20.3). Median progression-free survival by IRC assessment was 7.3 months (95% CI, 5.5-9.2). Median overall survival was 24.0 months (95% CI, 14.6-28.8). In the EXCLAIM cohort, median follow-up was 13.0 months, with confirmed ORR by IRC assessment of 25% (95% CI, 17%-35%) and by investigator assessment of 32% (95% CI, 23%-43%). The most common treatment-related adverse events were diarrhea and rash. CONCLUSIONS AND RELEVANCE: In this open-label, phase 1/2 nonrandomized clinical trial, mobocertinib was associated with clinically meaningful benefit in patients with previously treated EGFRex20ins-positive mNSCLC, with a manageable safety profile. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02716116
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spelling pubmed-85178852021-10-29 Treatment Outcomes and Safety of Mobocertinib in Platinum-Pretreated Patients With EGFR Exon 20 Insertion–Positive Metastatic Non–Small Cell Lung Cancer: A Phase 1/2 Open-label Nonrandomized Clinical Trial Zhou, Caicun Ramalingam, Suresh S. Kim, Tae Min Kim, Sang-We Yang, James Chih-Hsin Riely, Gregory J. Mekhail, Tarek Nguyen, Danny Garcia Campelo, Maria R. Felip, Enriqueta Vincent, Sylvie Jin, Shu Griffin, Celina Bunn, Veronica Lin, Jianchang Lin, Huamao M. Mehta, Minal Jänne, Pasi A. JAMA Oncol Original Investigation IMPORTANCE: Metastatic non–small cell lung cancer (mNSCLC) with EGFR exon 20 insertion (EGFRex20ins) mutations is associated with a poor prognosis. Mobocertinib is an oral tyrosine kinase inhibitor designed to selectively target EGFRex20ins mutations. OBJECTIVE: To evaluate treatment outcomes and safety of mobocertinib in patients with previously treated EGFRex20ins-positive mNSCLC. DESIGN, SETTING, AND PARTICIPANTS: This 3-part, open-label, phase 1/2 nonrandomized clinical trial with dose-escalation/dose-expansion cohorts (28 sites in the US) and a single-arm extension cohort (EXCLAIM; 40 sites in Asia, Europe, and North America) was conducted between June 2016 and November 2020 (data cutoff date). The primary analysis populations were the platinum-pretreated patients (PPP) cohort and the EXCLAIM cohort. The PPP cohort included 114 patients with platinum-pretreated EGFRex20ins-positive mNSCLC who received mobocertinib 160 mg once daily from the dose-escalation (n = 6), dose-expansion (n = 22), and EXCLAIM (n = 86) cohorts. The EXCLAIM cohort included 96 patients with previously treated EGFRex20ins-positive mNSCLC (10 were not platinum pretreated and thus were excluded from the PPP cohort). INTERVENTIONS: Mobocertinib 160 mg once daily. MAIN OUTCOMES AND MEASURES: The primary end point of the PPP and EXCLAIM cohorts was confirmed objective response rate (ORR) assessed by independent review committee (IRC). Secondary end points included confirmed ORR by investigator, duration of response, progression-free survival, overall survival, and safety. RESULTS: Among the PPP (n = 114) and EXCLAIM (n = 96) cohorts, the median (range) age was 60 (27-84) and 59 (27-80) years, respectively; most patients were women (75 [66%] and 62 [65%], respectively) and of Asian race (68 [60%] and 66 [69%], respectively). At data cutoff, median follow-up was 14.2 months in the PPP cohort (median 2 prior anticancer regimens; 40 [35%] had baseline brain metastases), with confirmed ORR of 28% (95% CI, 20%-37%) by IRC assessment and 35% (95% CI, 26%-45%) by investigator assessment; median duration of response by IRC assessment was 17.5 months (95% CI, 7.4-20.3). Median progression-free survival by IRC assessment was 7.3 months (95% CI, 5.5-9.2). Median overall survival was 24.0 months (95% CI, 14.6-28.8). In the EXCLAIM cohort, median follow-up was 13.0 months, with confirmed ORR by IRC assessment of 25% (95% CI, 17%-35%) and by investigator assessment of 32% (95% CI, 23%-43%). The most common treatment-related adverse events were diarrhea and rash. CONCLUSIONS AND RELEVANCE: In this open-label, phase 1/2 nonrandomized clinical trial, mobocertinib was associated with clinically meaningful benefit in patients with previously treated EGFRex20ins-positive mNSCLC, with a manageable safety profile. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02716116 American Medical Association 2021-10-14 2021-12 /pmc/articles/PMC8517885/ /pubmed/34647988 http://dx.doi.org/10.1001/jamaoncol.2021.4761 Text en Copyright 2021 Zhou C et al. JAMA Oncology. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article distributed under the terms of the CC-BY-NC-ND License.
spellingShingle Original Investigation
Zhou, Caicun
Ramalingam, Suresh S.
Kim, Tae Min
Kim, Sang-We
Yang, James Chih-Hsin
Riely, Gregory J.
Mekhail, Tarek
Nguyen, Danny
Garcia Campelo, Maria R.
Felip, Enriqueta
Vincent, Sylvie
Jin, Shu
Griffin, Celina
Bunn, Veronica
Lin, Jianchang
Lin, Huamao M.
Mehta, Minal
Jänne, Pasi A.
Treatment Outcomes and Safety of Mobocertinib in Platinum-Pretreated Patients With EGFR Exon 20 Insertion–Positive Metastatic Non–Small Cell Lung Cancer: A Phase 1/2 Open-label Nonrandomized Clinical Trial
title Treatment Outcomes and Safety of Mobocertinib in Platinum-Pretreated Patients With EGFR Exon 20 Insertion–Positive Metastatic Non–Small Cell Lung Cancer: A Phase 1/2 Open-label Nonrandomized Clinical Trial
title_full Treatment Outcomes and Safety of Mobocertinib in Platinum-Pretreated Patients With EGFR Exon 20 Insertion–Positive Metastatic Non–Small Cell Lung Cancer: A Phase 1/2 Open-label Nonrandomized Clinical Trial
title_fullStr Treatment Outcomes and Safety of Mobocertinib in Platinum-Pretreated Patients With EGFR Exon 20 Insertion–Positive Metastatic Non–Small Cell Lung Cancer: A Phase 1/2 Open-label Nonrandomized Clinical Trial
title_full_unstemmed Treatment Outcomes and Safety of Mobocertinib in Platinum-Pretreated Patients With EGFR Exon 20 Insertion–Positive Metastatic Non–Small Cell Lung Cancer: A Phase 1/2 Open-label Nonrandomized Clinical Trial
title_short Treatment Outcomes and Safety of Mobocertinib in Platinum-Pretreated Patients With EGFR Exon 20 Insertion–Positive Metastatic Non–Small Cell Lung Cancer: A Phase 1/2 Open-label Nonrandomized Clinical Trial
title_sort treatment outcomes and safety of mobocertinib in platinum-pretreated patients with egfr exon 20 insertion–positive metastatic non–small cell lung cancer: a phase 1/2 open-label nonrandomized clinical trial
topic Original Investigation
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8517885/
https://www.ncbi.nlm.nih.gov/pubmed/34647988
http://dx.doi.org/10.1001/jamaoncol.2021.4761
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