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Mini Oral session

26MO - Efficacy and safety of poziotinib in treatment-naïve HER2 exon 20 insertion (ex20ins) mutated non-small cell lung cancer (NSCLC): ZENITH20-4

Date

07 Mar 2022

Session

Mini Oral session

Presenters

Sophie Sun

Citation

Annals of Oncology (2022) 33 (suppl_1): S13-S23. 10.1016/annonc/annonc840

Authors

S. Sun1, A. Prelaj2, C. Baik3, X. Le4, M. Garassino5, M. Wollner6, E. Haura7, Z. Piotrowska8, M. Socinski9, L. Dreiling10, G. Bhat10, F. Lebel10, R. Cornelissen11

Author affiliations

  • 1 BC Cancer Agency - Vancouver, Vancouver/CA
  • 2 Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 - Milan/IT
  • 3 Seattle Cancer Care Alliance, Seattle/US
  • 4 UT MD Anderson Cancer Center, 77030 - Houston/US
  • 5 Istituto Nazionale dei Tumori di Milano- Fondazione IRCCS, Milan/IT
  • 6 Rambam Healthcare Campus, 3109601 - Haifa/IL
  • 7 H. Lee Moffitt Cancer Center & Research Institute, 33612 - Tampa/US
  • 8 Massachusetts General Hospital, Boston/US
  • 9 Advent Health, 32804 - Orlando/US
  • 10 Spectrum Pharmaceuticals, Irvine/US
  • 11 Erasmus University Medical Center, 3015 CE - Rotterdam/NL
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Resources

Abstract 26MO

Background

Patients (pts) with advanced NSCLC harboring HER2 ex20ins mutations have a poor prognosis with no approved targeted therapy. Poziotinib is a potent tyrosine kinase inhibitor (TKI) able to target the inaccessible binding pocket of ex20ins. Cohort 4 of the ZENITH20 phase 2 study aims to evaluate the clinical efficacy of poziotinib in treatment-naïve pts with advanced HER2 ex20ins NSCLC. Preliminary efficacy and safety of QD dosing in this cohort were presented previously. Here, we present the primary efficacy analysis of the full cohort of 70 patients.

Methods

ZENITH20-4 enrolled pts with locally advanced or metastatic treatment-naïve advanced HER2 ex20ins NSCLC. Poziotinib was administered orally 16 mg QD or 8 mg BID, with optional dose interruptions/reductions for toxicity. The primary endpoint was objective response rate (ORR) by independent review (RECIST 1.1). Secondary endpoints included disease control rate (DCR), duration of response (DOR), progression-free survival (PFS), and safety.

Results

In total, 70 pts (QD, n = 48; BID, n = 22) were treated; 14 remain on study (n = 3 and n = 11, respectively). Demographics were representative of this population. Among those treated with QD and BID dosing, 90% and 68% had dose interruptions, and 79% and 64% required dose reductions, respectively. Treatment-related AEs of any grade occurred in all pts treated with QD and 86% (n = 19) of pts treated with BID dosing. Among grade 3 AEs, the most common were rash (n = 17 [35%]; n = 4 [18%]), stomatitis/mucosal inflammation (n = 10 [21%]; n = 3 [14%]), and diarrhea (n = 7 [15%]; n = 3 [14%]). Combined ORR was 41% (95% CI: 30%, 54%), and 4 pts had unconfirmed responses (uORR = 47%). DCR was 73%, median DoR was 5.7 months (range: 1.2, >19.1), with 34% of pts having a DOR of >6 months, and median PFS was 5.6 months (range: 0, >20.2).

Conclusions

For both QD and BID dosing regimens, poziotinib therapy demonstrated statistically significant clinically meaningful efficacy in pts receiving front-line treatment for HER2 ex20ins NSCLC. Tolerability was improved with BID dosing, and overall AEs were manageable with dose modifications.

Clinical trial identification

NCT03318939.

Editorial acknowledgement

Medical writing support was provided by Meghan Sullivan, PhD (MedVal Scientific Information Services, LLC), and was funded by Spectrum Pharmaceuticals, Inc.

Legal entity responsible for the study

Spectrum Pharmaceuticals, Inc.

Funding

Spectrum Pharmaceuticals, Inc.

Disclosure

S. Sun: Other, Personal, Other, Consultancy fees: AstraZeneca; Other, Personal, Other, Consultancy fees: Bristol Myers Squibb; Other, Personal, Other, Consultancy fees: Novartis; Other, Personal, Other, Consultancy fees: Pfizer; Other, Personal, Other, Consultancy fees: Takeda. A. Prelaj: Financial Interests, Personal, Other, Personal fees: Roche; Financial Interests, Personal and Institutional, Other, Personal fees: AstraZeneca; Financial Interests, Personal, Other, Personal fees: Bristol Myers Squibb. C. Baik: Financial Interests, Personal and Institutional, Other, Research funding and Consultancy fees: AstraZeneca; Financial Interests, Personal and Institutional, Other, Research funding and Consultancy fees: Blueprint Medicines; Financial Interests, Personal and Institutional, Other, Research funding and Consultancy fees: Daiichi Sankyo; Financial Interests, Personal and Institutional, Other, Research funding and Consultancy fees: Turning Point Therapeutics; Financial Interests, Personal, Other, Consultancy fees: Guardant; Financial Interests, Personal, Other, Consultancy fees: Regeneron; Financial Interests, Personal, Other, Consultancy fees: Silverback; Financial Interests, Personal, Other, Consultancy fees: Takeda; Financial Interests, Institutional, Funding: AbbVie; Financial Interests, Institutional, Funding: Genentech; Financial Interests, Institutional, Funding: Janssen; Financial Interests, Institutional, Funding: Eli Lilly; Financial Interests, Institutional, Funding: Loxo Oncology; Financial Interests, Institutional, Funding: Novartis; Financial Interests, Institutional, Funding: Pfizer; Financial Interests, Institutional, Funding: Rain Therapeutics; Financial Interests, Institutional, Funding: Spectrum. X. Le: Financial Interests, Personal and Institutional, Other, Research funding and Consulting/advisory fees: EMD Serono; Financial Interests, Personal, Other, Consulting/advisory fees: AstraZeneca; Financial Interests, Personal, Other, Consulting/advisory fees: Spectrum; Financial Interests, Personal, Other, Consulting/advisory fees: Novartis; Financial Interests, Personal and Institutional, Other, Research funding and Consulting/advisory fees: Eli Lilly; Financial Interests, Personal and Institutional, Other, Research funding and Consulting/advisory fees: Boehringer Ingelheim; Financial Interests, Personal, Other, Consulting/advisory fees: Hengrui; Financial Interests, Personal, Other, Consulting/advisory fees: Janssen; Financial Interests, Personal, Other, Consulting/advisory fees: AbbVie; Financial Interests, Institutional, Funding: Regeneron. M. Garassino: Financial Interests, Personal and Institutional, Other: AstraZeneca; Financial Interests, Personal and Institutional, Other: MSD International; Financial Interests, Institutional, Other: MSD; Financial Interests, Personal and Institutional, Other: Bristol Myers Squibb; Financial Interests, Personal and Institutional, Other: Boehringer Ingelheim Italia; Financial Interests, Personal and Institutional, Other: Celgene; Financial Interests, Personal and Institutional, Other: Eli Lilly; Financial Interests, Personal and Institutional, Other: Ignyta; Financial Interests, Personal and Institutional, Other: Incyte; Financial Interests, Personal, Other: Inivata; Financial Interests, Personal and Institutional, Other: MedImmune; Financial Interests, Personal and Institutional, Other: Novartis; Financial Interests, Personal and Institutional, Other: Pfizer; Financial Interests, Institutional, Other: Pfizer (MISP); Financial Interests, Personal and Institutional, Other: Roche; Financial Interests, Personal and Institutional, Other: Takeda; Financial Interests, Personal, Other: Seattle Genetics; Financial Interests, Personal, Other: Mirati; Financial Interests, Personal, Other: Daiichi Sankyo; Financial Interests, Personal, Other: Regeneron; Financial Interests, Personal, Other: Merck; Financial Interests, Institutional, Other: Tiziana; Financial Interests, Institutional, Other: Foundation Medicine; Financial Interests, Institutional, Other: GlaxoSmithKline; Financial Interests, Institutional, Other: Spectrum; Other, Personal and Institutional, Funding: AIRC; Other, Personal and Institutional, Funding: AIFA; Other, Personal and Institutional, Funding: Ministry of Health of Italy; Other, Personal and Institutional, Funding: TRANSCAN. M. Wollner: Financial Interests, Personal, Other, Honoraria: MSD; Financial Interests, Personal, Other, Honoraria: AstraZeneca; Financial Interests, Institutional, Advisory Role: Roche Israel; Financial Interests, Personal, Advisory Role: Takeda; Financial Interests, Personal, Advisory Role: Bristol Myers Squibb; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Speaker’s Bureau: Roche Israel; Financial Interests, Personal, Speaker’s Bureau: Boehringer Ingelheim; Financial Interests, Personal, Speaker’s Bureau: Novartis; Financial Interests, Personal, Speaker’s Bureau: Bristol Myers Squibb; Financial Interests, Institutional, Funding: MSD; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Pfizer; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Bristol Myers Squibb. E. Haura: Financial Interests, Personal and Institutional, Other, Principal investigator and Consultant: Revolution Medicines; Non-Financial Interests, Personal and Institutional, Other, Principal investigator and Consultant: Revolution Medicines; Non-Financial Interests, Personal, Other, Consultant: Janssen; Non-Financial Interests, Personal, Other, Consultant: Ellipses Pharma. Z. Piotrowska: Financial Interests, Personal, Advisory Board: Blueprint Medicines; Financial Interests, Personal, Other, Consulting: Daiichi Sankyo; Financial Interests, Personal, Advisory Board: Takeda; Financial Interests, Personal, Advisory Board: Cullinan; Financial Interests, Personal, Advisory Board: C4 Therapeutics; Financial Interests, Personal, Advisory Board: Janssen; Financial Interests, Personal, Advisory Board: Jazz Pharmaceuticals; Financial Interests, Personal, Advisory Board: Eli Lilly; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Genentech; Financial Interests, Institutional, Funding: Blueprint Medicines; Financial Interests, Institutional, Funding: Janssen; Financial Interests, Institutional, Funding: AbbVie; Financial Interests, Institutional, Funding: Daiichi Sankyo; Financial Interests, Institutional, Funding: Cullinan; Financial Interests, Institutional, Funding: Tesaro/GlaxoSmithKline; Financial Interests, Institutional, Funding: AstraZeneca; Financial Interests, Institutional, Funding: Spectrum; Financial Interests, Institutional, Funding: Takeda; Financial Interests, Institutional, Funding: Novartis. M. Socinski: Financial Interests, Personal, Other, Honoraria: Genentech; Financial Interests, Personal, Other, Honoraria: Bristol Myers Squibb; Financial Interests, Personal, Other, Honoraria: Celgene; Financial Interests, Personal, Other, Honoraria: AstraZeneca; Financial Interests, Personal, Other, Honoraria: Guardant Health; Financial Interests, Personal, Other, Honoraria: Bayer; Financial Interests, Personal, Other, Honoraria: Merck; Financial Interests, Personal, Other, Honoraria: Roche/Genentech; Financial Interests, Personal, Other, Honoraria: Eli Lilly; Financial Interests, Personal, Other, Honoraria: AstraZeneca/MedImmune; Financial Interests, Personal, Other, Honoraria: Janssen; Financial Interests, Personal, Other, Honoraria: Novartis; Financial Interests, Personal, Speaker’s Bureau: Genentech; Financial Interests, Personal, Speaker’s Bureau: Bristol Myers Squibb; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: Boehringer Ingelheim; Financial Interests, Personal, Speaker’s Bureau: Bayer; Financial Interests, Personal, Speaker’s Bureau: Merck; Financial Interests, Personal, Speaker’s Bureau: Amgen; Financial Interests, Personal, Speaker’s Bureau: Blueprint Medicines; Financial Interests, Personal, Speaker’s Bureau: G1 Therapeutics; Financial Interests, Personal, Speaker’s Bureau: Guardant Health; Financial Interests, Personal, Speaker’s Bureau: Eli Lilly; Financial Interests, Personal, Speaker’s Bureau: Regeneron/Sanofi; Financial Interests, Personal, Speaker’s Bureau: Jazz Pharmaceuticals; Financial Interests, Personal, Speaker’s Bureau: Janssen Oncology; Financial Interests, Institutional, Funding: Genentech; Financial Interests, Institutional, Funding: Spectrum; Financial Interests, Institutional, Funding: AstraZeneca/MedImmune. L. Dreiling: Financial Interests, Personal, Full or part-time Employment: Spectrum; Financial Interests, Personal, Stocks/Shares: Spectrum. G. Bhat: Financial Interests, Personal, Full or part-time Employment: Spectrum; Financial Interests, Personal, Stocks/Shares: Spectrum. F. Lebel: Financial Interests, Personal, Full or part-time Employment: Spectrum; Financial Interests, Personal, Stocks/Shares: Spectrum; Financial Interests, Personal, Leadership Role: Spectrum. All other authors have declared no conflicts of interest.

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