Abstract 1172P
Background
Poziotinib is an oral pan-ErbB tyrosine kinase inhibitor (TKI) with demonstrated clinical activity and an expected safety profile. Patients with NSCLC harboring HER2 exon 20 insertion mutations (ex20ins) have poor outcomes and lack approved targeted treatments. The G778_P780dup (G778) mutation is one of the most common, representing 9-19% of HER2 ex20ins in NSCLC. Previous studies have reported an overall response rate (ORR) ranging from 10-60% with TKIs in patients with G778. Here we report the effects of poziotinib in patients harboring the HER2 ex20ins G778 mutation in a relatively large population of treatment-naïve (C4) and previously treated (C2) patients with NSCLC.
Methods
ZENITH20 is a prospective global phase II study. Cohorts 2 and 4 (C2, C4) include adults with locally advanced or metastatic NSCLC harboring HER2 ex20ins. Tumor mutational status was assessed via next-generation sequencing. C2 patients received 16 mg poziotinib QD; C4 patients received 16 mg QD or 8 mg BID. The primary endpoint was ORR assessed by an Independent Radiologic Review Committee; secondary endpoints included disease control rate (DCR), duration of response (DoR), and safety.
Results
170 patients were enrolled, with n=90 in C2 and n=80 in C4, 14 of whom had the HER2 G778 GSP insertion (n=7 each in C2 and C4). Demographics were similar to the overall population (median age 59 yrs, 8/14 female, 8/14 never smokers). 12/14 patients were evaluable and showed 100% partial response (PR) with a median DoR of 5.5 months (range 2.9-14.1; 3/12 patients had a DoR > 6 mo [C2: n=1; C4: n=2]). Median progression-free survival (PFS) was 7.8 mo (C2: 7.6; C4: 9.8) and compared well against the overall cohorts that included non-G778 (previously reported as C2: 5.5; C4: 5.6 in Le JCO 2020 and Sun ESMO TAT 2022). Adverse effects (AEs) were similar to the TKI class (the most common being rash, stomatitis). No pneumonitis was reported.
Conclusions
Poziotinib is highly active in G778, a common HER2 ex20ins alteration, in both treatment-naïve and previously treated patients with NSCLC. The AE profile was typical of a TKI.
Clinical trial identification
NCT03318939.
Editorial acknowledgement
Medical writing and editorial assistance were provided by Nicole Day, PhD, of MedVal Scientific Information Services, LLC, and were funded by Spectrum Pharmaceuticals.
Legal entity responsible for the study
Spectrum Pharmaceuticals, Inc.
Funding
Spectrum Pharmaceuticals, Inc.
Disclosure
X. Le: Financial Interests, Personal, Other, Consulting/advisory fees: EMD Serono (Merck KGaA), AstraZeneca, Spectrum Pharmaceuticals, Novartis, Eli Lilly, Boehringer Ingelheim, Hengrui Therapeutics, Janssen, AbbVie; Financial Interests, Personal and Institutional, Funding, Research funding: Eli Lilly, EMD Serono (Merck KGaA), Regeneron, Boehringer Ingelheim. S. Sun: Financial Interests, Personal, Other, Consultancy fees: AstraZeneca, Bristol Myers Squibb, Novartis, Pfizer, Takeda. E. Haura: Other, Personal and Institutional, Research Grant: Revolution Medicines; Other, Personal and Institutional, Principal Investigator: Revolution Medicines; Other, Personal and Institutional, Other, Consultant: Revolution Medicines; Non-Financial Interests, Personal, Other, Consultant: Janssen, Ellipses Pharma. E. Bertino: Financial Interests, Personal, Other, Personal fees: Pfizer, Boehringer Ingelheim, Takeda; Non-Financial Interests, Personal, Other, Non-financial support: Merck, Eli Lilly; Financial Interests, Personal and Institutional, Research Grant: Ohio State Intramural Research Program. C. Baik: Financial Interests, Personal, Other, Consultancy fees: Takeda, Guardant Health, Regeneron, Silverback Therapeutics; Financial Interests, Personal and Institutional, Other, Research funding and consultancy fees: Turning Point Therapeutics, AstraZeneca, Blueprint Medicines, Daiichi Sankyo; Financial Interests, Institutional, Funding: Loxo Oncology, AbbVie, Spectrum Pharmaceuticals, Pfizer, Rain Therapeutics, Janssen, Lilly Oncology. H. Mamdani: Other, Personal, Other, Personal fees, consultancy, and non-financial support: AstraZeneca; Financial Interests, Personal, Other, Personal fees and consultancy: Zentalis; Other, Personal, Other, Consultancy and non-financial support: Caris Life Science, Takeda; Financial Interests, Personal and Institutional, Research Grant: Zentalis; Financial Interests, Institutional, Research Grant: AstraZeneca. S. Leu: Financial Interests, Personal, Full or part-time Employment: Spectrum Pharmaceuticals. A. Thiagalingam, J. Kokhreidze: Financial Interests, Personal, Full or part-time Employment: Spectrum Pharmaceuticals; Financial Interests, Personal, Other, Stock and Other Ownership Interests: Spectrum Pharmaceuticals. F. Lebel: Financial Interests, Personal, Full or part-time Employment: Spectrum Pharmaceuticals; Financial Interests, Personal, Other, Stock and Other Ownership Interests: Spectrum Pharmaceuticals; Non-Financial Interests, Personal, Leadership Role: Spectrum Pharmaceuticals. M.A. Socinski: Financial Interests, Personal, Other, Honoraria: Genentech, Bristol Myers Squibb, Celgene, AstraZeneca, Guardant Health, Bayer, Merck, Roche/Genentech, Eli Lilly, AstraZeneca/MedImmune, Janssen, Novartis; Financial Interests, Personal, Speaker’s Bureau: Genentech, Bristol Myers Squibb, AstraZeneca, Boehringer Ingelheim, Bayer, Merck, Amgen, Blueprint Medicines, G1 Therapeutics, Guardant Health, Eli Lilly, Regeneron/Sanofi, Jazz Pharmaceuticals, Janssen Oncology; Financial Interests, Institutional, Funding: Genentech, Spectrum Pharmaceuticals, AstraZeneca/MedImmune.