Poziotinib in Treatment-Naive NSCLC Harboring HER2 Exon 20 Mutations: ZENITH20-4, A Multicenter, Multicohort, Open-Label, Phase 2 Trial (Cohort 4)

Robin Cornelissen; Arsela Prelaj; ZENITH20-4 Investigators; Sophie Sun; Christina Baik; Mirjana Wollner; Eric B. Haura; Hirva Mamdani; Jonathan W. Riess; Federico Cappuzzo; Marina C. Garassino; John V. Heymach; Mark A. Socinski; Szu Yun Leu; Gajanan Bhat; Francois Lebel; Xiuning Le

doi:10.1016/j.jtho.2023.03.016

Poziotinib in Treatment-Naive NSCLC Harboring HER2 Exon 20 Mutations: ZENITH20-4, A Multicenter, Multicohort, Open-Label, Phase 2 Trial (Cohort 4)

Robin Cornelissen, Arsela Prelaj, ZENITH20-4 Investigators, Sophie Sun, Christina Baik, Mirjana Wollner, Eric B. Haura, Hirva Mamdani, Jonathan W. Riess, Federico Cappuzzo, Marina C. Garassino, John V. Heymach, Mark A. Socinski, Szu Yun Leu, Gajanan Bhat, Francois Lebel, Xiuning Le^*

^*Corresponding author for this work

Pulmonary Medicine

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

20 Citations (Scopus)

Abstract

Introduction: ERBB2 or HER2 alterations are found in approximately 2% to 5% of NSCLCs; most are exon 20 insertion mutations. The efficacy and safety of poziotinib, an oral tyrosine kinase inhibitor, were assessed in patients with treatment-naive NSCLC whose tumors harbor HER2 exon 20 insertions. Methods: ZENITH20 is an open-label, multicohort, multicenter, global, phase 2 trial. ZENITH20-C4 enrolled treatment-naive patients with NSCLC with tumors harboring HER2 exon 20 insertions. Poziotinib was administered 16 mg once daily (QD) or 8 mg twice daily (BID). The primary end point was objective response rate (ORR) by independent central review. Secondary and exploratory end points included disease control rate, duration of response, progression-free survival, and safety. Results: A total of 80 patients (16 mg QD, n = 47; 8 mg BID, n = 33) were treated in ZENITH20-C4. ORR was 39% (95% confidence interval [CI]: 28%–50%; 31 of 80), with a disease control rate of 73% (95% CI: 61%–82%; 58 of 80); 80% of the patients experienced tumor reduction. Median duration of response was 5.7 (95% CI: 4.6–11.9) months, and median progression-free survival was 5.6 (95% CI: 5.4–7.3) months. The most common grade 3 treatment-related adverse events were rash (QD, 45%; BID, 39%), stomatitis (QD, 21%; BID, 15%), and diarrhea (QD, 15%; BID, 21%). Among all subtypes of HER2 exon 20 insertions, seven patients (9%) harboring tumors with G778_P780dupGSP had the best clinical outcomes (ORR, 71%). Conclusions: Poziotinib was found to have clinically meaningful efficacy with a manageable toxicity profile for patients with treatment-naive NSCLC harboring HER2 exon 20 mutations.

Original language	English
Pages (from-to)	1031-1041
Number of pages	11
Journal	Journal of Thoracic Oncology
Volume	18
Issue number	8
Early online date	21 Mar 2023
DOIs	https://doi.org/10.1016/j.jtho.2023.03.016
Publication status	Published - Aug 2023

Bibliographical note

Funding Information:
This study was supported by the Spectrum Pharmaceuticals . The Spectrum Pharmaceuticals sponsored the design and conduct of the study; participated in collection, management, analysis, and interpretation of the data; assisted in preparation, review, and approval of the manuscript; and made the decision to submit the manuscript for publication. The authors thank Nicole Day, PhD, and Anthony DiLauro, PhD, of MedVal Scientific Information Services, LLC, for medical writing and editorial assistance, which were funded by Spectrum Pharmaceuticals. This manuscript was prepared according to the International Society for Medical Publication Professionals’ “Good Publication Practice for Communicating Company-Sponsored Medical Research: GPP3.”

Publisher Copyright:
© 2023

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10.1016/j.jtho.2023.03.016

Cite this

Cornelissen, R., Prelaj, A., ZENITH20-4 Investigators, Sun, S., Baik, C., Wollner, M., Haura, E. B., Mamdani, H., Riess, J. W., Cappuzzo, F., Garassino, M. C., Heymach, J. V., Socinski, M. A., Leu, S. Y., Bhat, G., Lebel, F., & Le, X. (2023). Poziotinib in Treatment-Naive NSCLC Harboring HER2 Exon 20 Mutations: ZENITH20-4, A Multicenter, Multicohort, Open-Label, Phase 2 Trial (Cohort 4). Journal of Thoracic Oncology, 18(8), 1031-1041. https://doi.org/10.1016/j.jtho.2023.03.016

@article{0f89f604ce5e41c495cf499e8740c9a0,

title = "Poziotinib in Treatment-Naive NSCLC Harboring HER2 Exon 20 Mutations: ZENITH20-4, A Multicenter, Multicohort, Open-Label, Phase 2 Trial (Cohort 4)",

abstract = "Introduction: ERBB2 or HER2 alterations are found in approximately 2% to 5% of NSCLCs; most are exon 20 insertion mutations. The efficacy and safety of poziotinib, an oral tyrosine kinase inhibitor, were assessed in patients with treatment-naive NSCLC whose tumors harbor HER2 exon 20 insertions. Methods: ZENITH20 is an open-label, multicohort, multicenter, global, phase 2 trial. ZENITH20-C4 enrolled treatment-naive patients with NSCLC with tumors harboring HER2 exon 20 insertions. Poziotinib was administered 16 mg once daily (QD) or 8 mg twice daily (BID). The primary end point was objective response rate (ORR) by independent central review. Secondary and exploratory end points included disease control rate, duration of response, progression-free survival, and safety. Results: A total of 80 patients (16 mg QD, n = 47; 8 mg BID, n = 33) were treated in ZENITH20-C4. ORR was 39% (95% confidence interval [CI]: 28%–50%; 31 of 80), with a disease control rate of 73% (95% CI: 61%–82%; 58 of 80); 80% of the patients experienced tumor reduction. Median duration of response was 5.7 (95% CI: 4.6–11.9) months, and median progression-free survival was 5.6 (95% CI: 5.4–7.3) months. The most common grade 3 treatment-related adverse events were rash (QD, 45%; BID, 39%), stomatitis (QD, 21%; BID, 15%), and diarrhea (QD, 15%; BID, 21%). Among all subtypes of HER2 exon 20 insertions, seven patients (9%) harboring tumors with G778_P780dupGSP had the best clinical outcomes (ORR, 71%). Conclusions: Poziotinib was found to have clinically meaningful efficacy with a manageable toxicity profile for patients with treatment-naive NSCLC harboring HER2 exon 20 mutations.",

author = "Robin Cornelissen and Arsela Prelaj and {ZENITH20-4 Investigators} and Sophie Sun and Christina Baik and Mirjana Wollner and Haura, {Eric B.} and Hirva Mamdani and Riess, {Jonathan W.} and Federico Cappuzzo and Garassino, {Marina C.} and Heymach, {John V.} and Socinski, {Mark A.} and Leu, {Szu Yun} and Gajanan Bhat and Francois Lebel and Xiuning Le",

note = "Funding Information: This study was supported by the Spectrum Pharmaceuticals . The Spectrum Pharmaceuticals sponsored the design and conduct of the study; participated in collection, management, analysis, and interpretation of the data; assisted in preparation, review, and approval of the manuscript; and made the decision to submit the manuscript for publication. The authors thank Nicole Day, PhD, and Anthony DiLauro, PhD, of MedVal Scientific Information Services, LLC, for medical writing and editorial assistance, which were funded by Spectrum Pharmaceuticals. This manuscript was prepared according to the International Society for Medical Publication Professionals{\textquoteright} “Good Publication Practice for Communicating Company-Sponsored Medical Research: GPP3.” Publisher Copyright: {\textcopyright} 2023",

year = "2023",

month = aug,

doi = "10.1016/j.jtho.2023.03.016",

language = "English",

volume = "18",

pages = "1031--1041",

journal = "Journal of Thoracic Oncology",

issn = "1556-0864",

publisher = "Elsevier Inc.",

number = "8",

}

Cornelissen, R, Prelaj, A, ZENITH20-4 Investigators, Sun, S, Baik, C, Wollner, M, Haura, EB, Mamdani, H, Riess, JW, Cappuzzo, F, Garassino, MC, Heymach, JV, Socinski, MA, Leu, SY, Bhat, G, Lebel, F & Le, X 2023, 'Poziotinib in Treatment-Naive NSCLC Harboring HER2 Exon 20 Mutations: ZENITH20-4, A Multicenter, Multicohort, Open-Label, Phase 2 Trial (Cohort 4)', Journal of Thoracic Oncology, vol. 18, no. 8, pp. 1031-1041. https://doi.org/10.1016/j.jtho.2023.03.016

Poziotinib in Treatment-Naive NSCLC Harboring HER2 Exon 20 Mutations: ZENITH20-4, A Multicenter, Multicohort, Open-Label, Phase 2 Trial (Cohort 4). / Cornelissen, Robin; Prelaj, Arsela; ZENITH20-4 Investigators et al.
In: Journal of Thoracic Oncology, Vol. 18, No. 8, 08.2023, p. 1031-1041.

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

TY - JOUR

T1 - Poziotinib in Treatment-Naive NSCLC Harboring HER2 Exon 20 Mutations

T2 - ZENITH20-4, A Multicenter, Multicohort, Open-Label, Phase 2 Trial (Cohort 4)

AU - Cornelissen, Robin

AU - Prelaj, Arsela

AU - ZENITH20-4 Investigators

AU - Sun, Sophie

AU - Baik, Christina

AU - Wollner, Mirjana

AU - Haura, Eric B.

AU - Mamdani, Hirva

AU - Riess, Jonathan W.

AU - Cappuzzo, Federico

AU - Garassino, Marina C.

AU - Heymach, John V.

AU - Socinski, Mark A.

AU - Leu, Szu Yun

AU - Bhat, Gajanan

AU - Lebel, Francois

AU - Le, Xiuning

N1 - Funding Information: This study was supported by the Spectrum Pharmaceuticals . The Spectrum Pharmaceuticals sponsored the design and conduct of the study; participated in collection, management, analysis, and interpretation of the data; assisted in preparation, review, and approval of the manuscript; and made the decision to submit the manuscript for publication. The authors thank Nicole Day, PhD, and Anthony DiLauro, PhD, of MedVal Scientific Information Services, LLC, for medical writing and editorial assistance, which were funded by Spectrum Pharmaceuticals. This manuscript was prepared according to the International Society for Medical Publication Professionals’ “Good Publication Practice for Communicating Company-Sponsored Medical Research: GPP3.” Publisher Copyright: © 2023

PY - 2023/8

Y1 - 2023/8

N2 - Introduction: ERBB2 or HER2 alterations are found in approximately 2% to 5% of NSCLCs; most are exon 20 insertion mutations. The efficacy and safety of poziotinib, an oral tyrosine kinase inhibitor, were assessed in patients with treatment-naive NSCLC whose tumors harbor HER2 exon 20 insertions. Methods: ZENITH20 is an open-label, multicohort, multicenter, global, phase 2 trial. ZENITH20-C4 enrolled treatment-naive patients with NSCLC with tumors harboring HER2 exon 20 insertions. Poziotinib was administered 16 mg once daily (QD) or 8 mg twice daily (BID). The primary end point was objective response rate (ORR) by independent central review. Secondary and exploratory end points included disease control rate, duration of response, progression-free survival, and safety. Results: A total of 80 patients (16 mg QD, n = 47; 8 mg BID, n = 33) were treated in ZENITH20-C4. ORR was 39% (95% confidence interval [CI]: 28%–50%; 31 of 80), with a disease control rate of 73% (95% CI: 61%–82%; 58 of 80); 80% of the patients experienced tumor reduction. Median duration of response was 5.7 (95% CI: 4.6–11.9) months, and median progression-free survival was 5.6 (95% CI: 5.4–7.3) months. The most common grade 3 treatment-related adverse events were rash (QD, 45%; BID, 39%), stomatitis (QD, 21%; BID, 15%), and diarrhea (QD, 15%; BID, 21%). Among all subtypes of HER2 exon 20 insertions, seven patients (9%) harboring tumors with G778_P780dupGSP had the best clinical outcomes (ORR, 71%). Conclusions: Poziotinib was found to have clinically meaningful efficacy with a manageable toxicity profile for patients with treatment-naive NSCLC harboring HER2 exon 20 mutations.

AB - Introduction: ERBB2 or HER2 alterations are found in approximately 2% to 5% of NSCLCs; most are exon 20 insertion mutations. The efficacy and safety of poziotinib, an oral tyrosine kinase inhibitor, were assessed in patients with treatment-naive NSCLC whose tumors harbor HER2 exon 20 insertions. Methods: ZENITH20 is an open-label, multicohort, multicenter, global, phase 2 trial. ZENITH20-C4 enrolled treatment-naive patients with NSCLC with tumors harboring HER2 exon 20 insertions. Poziotinib was administered 16 mg once daily (QD) or 8 mg twice daily (BID). The primary end point was objective response rate (ORR) by independent central review. Secondary and exploratory end points included disease control rate, duration of response, progression-free survival, and safety. Results: A total of 80 patients (16 mg QD, n = 47; 8 mg BID, n = 33) were treated in ZENITH20-C4. ORR was 39% (95% confidence interval [CI]: 28%–50%; 31 of 80), with a disease control rate of 73% (95% CI: 61%–82%; 58 of 80); 80% of the patients experienced tumor reduction. Median duration of response was 5.7 (95% CI: 4.6–11.9) months, and median progression-free survival was 5.6 (95% CI: 5.4–7.3) months. The most common grade 3 treatment-related adverse events were rash (QD, 45%; BID, 39%), stomatitis (QD, 21%; BID, 15%), and diarrhea (QD, 15%; BID, 21%). Among all subtypes of HER2 exon 20 insertions, seven patients (9%) harboring tumors with G778_P780dupGSP had the best clinical outcomes (ORR, 71%). Conclusions: Poziotinib was found to have clinically meaningful efficacy with a manageable toxicity profile for patients with treatment-naive NSCLC harboring HER2 exon 20 mutations.

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DO - 10.1016/j.jtho.2023.03.016

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SN - 1556-0864

VL - 18

SP - 1031

EP - 1041

JO - Journal of Thoracic Oncology

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IS - 8

ER -

Poziotinib in Treatment-Naive NSCLC Harboring HER2 Exon 20 Mutations: ZENITH20-4, A Multicenter, Multicohort, Open-Label, Phase 2 Trial (Cohort 4)

Abstract

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