Poziotinib for Patients With HER2 Exon 20 Mutant Non-Small-Cell Lung Cancer: Results From a Phase II Trial

Abstract

Purpose: Targeted therapies against non-small-cell lung cancer (NSCLC) harboring HER2 mutations remain an unmet need. In this study, we assessed the efficacy and safety of poziotinib in patients with HER2 exon 20 mutant advanced NSCLC in a single-arm, open-label, phase II study.

Patients and methods: Patients with advanced HER2 exon 20 mutant NSCLC were enrolled to receive poziotinib at a dose of 16 mg/d for 28-day cycles. The primary end point was objective response rate per RECIST version 1.1. Confirmatory scans were performed at least 28 days from initial radiologic response.

Results: Thirty patients received poziotinib treatment. At baseline, 90% of patients received prior platinum-based chemotherapy and 53% had two lines or more prior systemic therapies. As of data cutoff on March 1, 2021, the confirmed objective response rate was 27% (95% CI, 12 to 46). Responses were observed across HER2 exon 20 mutation subtypes. The median duration of response was 5.0 months (95% CI, 4.0 to not estimable). The median progression-free survival was 5.5 months (95% CI, 4.0 to 7.0). The median overall survival was 15 months (95% CI, 9.0 to not estimable). The most common grade 3 treatment-related adverse events were skin rash (47%) and diarrhea (20%). There was one possible treatment-related death because of pneumonitis.

Conclusion: Poziotinib showed promising antitumor activity in patients with HER2 exon 20 mutant NSCLC including patients who had previously received platinum-based chemotherapy.

Trial registration: ClinicalTrials.gov NCT03066206.

Conflict of interest statement

Yasir Y. ElaminConsulting or Advisory Role: Lilly, AstraZeneca, Turning Point TherapeuticsResearch Funding: Spectrum Pharmaceuticals, AstraZeneca, Takeda, Xcovery, Lilly, Elevation Oncology, Turning Point TherapeuticsTravel, Accommodations, Expenses: Lilly Jacqulyne P. RobichauxResearch Funding: Spectrum Pharmaceuticals, TakedaPatents, Royalties, Other Intellectual Property: Licensing agreement between Spectrum and MD Anderson (including myself) regarding intellectual property for treatment of EGFR and HER2 exon 20 mutations, Patent application Mehmet AltanConsulting or Advisory Role: GlaxoSmithKline, Shattuck LabsResearch Funding: Lilly, Bristol Myers Squibb, Novartis, GlaxoSmithKline, Jounce Therapeutics, Adaptimmune, Genentech, Nektar, Shattuck Labs Don L. GibbonsStock and Other Ownership Interests: Exact Sciences, NektarConsulting or Advisory Role: Sanofi, GlaxoSmithKline, Janssen Research & Development, Ribon Therapeutics, Mitobridge, Lilly, Menarini, Napa TherapeuticsResearch Funding: Janssen Research & Development, Takeda, AstraZeneca, Mitobridge, Ribon Therapeutics, Boehringer Ingelheim, Mirati Therapeutics, NGM BiopharmaceuticalsTravel, Accommodations, Expenses: AstraZeneca/MedImmune, BerGenBio, Takeda Vincent K. LamConsulting or Advisory Role: Takeda, Seattle Genetics, Bristol Myers SquibbResearch Funding: Guardant Health, Takeda, GlaxoSmithKline, Bristol Myers Squibb Anisha B. PatelConsulting or Advisory Role: OnQuality Pharmaceuticals, Novartis, Deciphera, NanOlogyResearch Funding: Lutris, Pfizer, OnQuality PharmaceuticalsTravel, Accommodations, Expenses: Novartis, OnQuality Pharmaceuticals Marcelo V. NegraoConsulting or Advisory Role: Mirati TherapeuticsResearch Funding: Mirati Therapeutics, AstraZeneca, Pfizer, Novartis, ZIOPHARM Oncology, Checkmate Pharmaceuticals Xiuning LeConsulting or Advisory Role: AstraZeneca, Lilly, EMD Serono, Spectrum Pharmaceuticals, Daiichi Sankyo/LillyResearch Funding: Lilly, Boehringer Ingelheim Jianjun ZhangHonoraria: Roche, Sino-USA Biomedical Platform, Geneplus, Origimed, Innovent Biologics, CancerNet, Zhejiang Cancer Hospital, Geneplus, Innovent Biologics, Zhejiang Cancer HospitalConsulting or Advisory Role: AstraZeneca, Geneplus, Capital Medical University, Johnson & Johnson/JanssenResearch Funding: MerckTravel, Accommodations, Expenses: Innovent Biologics, Zhejiang Cancer Hospital George Blumenschein JrEmployment: Janssen (I), Johnson & Johnson (I)Stock and Other Ownership Interests: Virogin BiotechConsulting or Advisory Role: Bristol Myers Squibb, Bayer, Celgene, Clovis Oncology, AbbVie, ARIAD, Genentech, Novartis, Xcovery, Adicet, Amgen, AstraZeneca, Roche, MedImmune, Maverick Therapeutics, Johnson & Johnson (I), Virogin Biotech, Gilead Sciences, Daiichi Sankyo Inc, Novartis, Tyme, Janssen Oncology, Lilly, InstilResearch Funding: Merck, Celgene, Genentech, Xcovery, Novartis, Bristol Myers Squibb, GlaxoSmithKline, Adaptimmune, Macrogenics, Kite Pharma, Immatics, Torque, Incyte, MedImmune, Exelixis, Immunocore, Roche, AstraZeneca, Bayer, Tmunity Therapeutics, Inc, Regeneron, BeiGene, Repertoire Immune Medicines, Daiichi Sankyo Inc, Verastem Anne S. TsaoConsulting or Advisory Role: Novartis, Boehringer Ingelheim, Genentech/Roche, Lilly, Bristol Myers Squibb, Epizyme, AstraZeneca/MedImmune, ARIAD, EMD Serono, Takeda, HERONResearch Funding: Merck, Genentech/Roche, Seattle Genetics, Millennium, Bristol Myers Squibb, Boehringer Ingelheim, Polaris, EMD Serono, Seattle Genetics, TakedaPatents, Royalties, Other Intellectual Property: UptoDate John V. HeymachStock and Other Ownership Interests: Cardinal Spine, Bio-TreeConsulting or Advisory Role: AstraZeneca, Bristol Myers Squibb, Spectrum Pharmaceuticals, Guardant Health, Hengrui Pharmaceutical, GlaxoSmithKline, EMD Serono, Lilly, Takeda, Sanofi/Aventis, Genentech/Roche, Boehringer Ingelheim, Catalyst Biotech, Foundation medicine, Novartis, Mirati Therapeutics, BrightPath Biotheraputics, Janssen, Nexus Health Systems, Pneuma Respiratory, Kairos Ventures, Roche, Leads BiolabsResearch Funding: AstraZeneca, Spectrum Pharmaceuticals, GlaxoSmithKlinePatents, Royalties, Other Intellectual Property: Licensing agreement between Spectrum and MD Anderson (including myself) regarding intellectual property for treatment of EGFR and HER2 exon 20 mutationsNo other potential conflicts of interest were reported.

Figures

FIG 1.

Waterfall plot of best response. DCR, disease control rate; ORR, objective response rate.

FIG 2.

(A) Kaplan-Meier estimate of DoR. (B) Kaplan-Meier estimate of PFS. DoR, duration of response; NE, not estimable; PFS, progression-free survival.

FIG 3.

Swimmers plot of poziotinib treatment duration. Each bar denotes a single patient. P indicates patient received previous platinum-based therapy and I indicates patient received previous immunotherapy. Additional previous treatments for each patient can be found in Appendix Table A1.

FIG A1.

Trial schema. EGFR, epidermal growth factor receptor; DoR, duration of response; HER2, human epidermal growth factor receptor 2; NSCLC, non–small-cell lung cancer; ORR, objective response rate; OS, overall survival; PD, disease progression; PFS, progression-free survival.

FIG A2.

Trial profile. HER2, human epidermal growth factor receptor 2.

FIG A3.

Kaplan-Meier estimate of OS. NE, not estimable; OS, overall survival.