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A Phase 2 Study of Poziotinib in Patients With Non-Small Cell Lung Cancer (NSCLC), Locally Advanced or Metastatic, With EGFR or HER2 Exon 20 Insertion Mutation (ZENITH20)

Description

Brief Summary
This is a Phase 2, open-label, multicenter study to evaluate the efficacy and the safety/tolerability of poziotinib in four patient cohorts for up to 174 previously treated NSCLC patients with any systemic therapy (Cohort 1: 87 patients with EGFR exon 20 insertion mutations, Cohort 2: 87 patients with HER2 exon 20 insertion mutations), up to 140 treatment-naive NSCLC patients (Cohort 3: 70 patients with EGFR exon 20 insertion mutations, Cohort 4: 70 patients with HER2 exon 20 insertion mutations). For Amendment 2, approximately 180 patients in Cohort 5 (60 patients per dose group), 30 patients in Cohort 6, and 30 patients in Cohort 7 are being added.


Detailed Description
The Screening period (Day -30 to Day -1) lasts up to approximately 30 days prior to Cycle 1, Day 1. Patients must meet all Inclusion/Exclusion Criteria to participate in the study. Eligible patients will provide written Informed Consent prior to undergoing any study procedures. Each treatment cycle is 28 calendar days in duration. There will be seven patient cohorts and eligible patients will be enrolled into each cohort in parallel based on EGFR or HER2 exon 20 mutation status and prior treatment status: - Cohort 1: Previously treated patients with EGFR exon 20 insertion mutation positive NSCLC (closed to enrollment) - Cohort 2: Previously treated patients with HER2 exon 20 insertion mutation positive NSCLC (closed to enrollment) - Cohort 3: Treatment naïve patients with EGFR exon 20 insertion mutation positive NSCLC - Cohort 4: Treatment naïve patients with HER2 exon 20 insertion mutation positive NSCLC - Cohort 5: Patients who meet the criteria for enrollment in Cohort 1 to 4, but the enrollment in the respective cohort has been closed - Cohort 6: Patients with acquired EGFR mutation who progressed while on treatment with first-line osimertinib - Cohort 7: Patients with EGFR or HER2 activating mutations Toxicity will be assessed based on the grade of the adverse events using CTCAE version 4.03. All treatments will be taken orally, once daily (QD) at approximately the same time each morning. On Day 1 of each 28-day cycle, the patient's absolute neutrophil count (ANC) must be ≥1.5×10^9/L and platelet count must be ≥100×10^9/L before administering poziotinib. All patients will be treated 28 days per cycle until 24 months of treatment, disease progression (except for first progression in Cohort 5), death, intolerable adverse events (AEs), or other protocol-specified reasons for patient withdrawal.

Phase

N/A

Inclusion and Exclusion Criteria

  • Patient must be willing and capable of giving written Informed Consent, adhering to dosing and visit schedules, and meeting all study requirements
  • Patient has histologically or cytologically confirmed locally advanced or metastatic non-small cell lung cancer (NSCLC) that is not amenable to treatment with curative intent
  • Prior treatment status:
  • Cohorts 1 and 2: Patient has had at least one prior systemic treatment for locally advanced or metastatic NSCLC
  • Cohorts 3 and 4: Patient is treatment-naïve for locally advanced or metastatic NSCLC and eligible to receive first-line treatment with poziotinib as determined by the Investigator. Adjuvant/neo-adjuvant therapies (chemotherapy, radiotherapy, or investigational agents) are permissible as long as they end at least 15 days prior to study entry.
  • Cohort 5: Patients who meet the criteria for enrollment in Cohort 1 to 4, but the enrollment in the respective cohort has been closed
  • Cohort 6: Patients with EGFR mutation-positive NSCLC who progressed while on treatment with first-line osimertinib
  • Cohort 7: Patient has had at least one prior systemic treatment for locally advanced or metastatic NSCLC
  • Specific mutations:
  • Cohort 1 and 3: Documented EGFR exon 20 insertion mutation
  • Cohort 2 and 4: Documented HER2 exon 20 insertion mutation
  • Cohort 5: Documented EGFR or HER2 exon 20 insertion mutations
  • Cohort 6: Documented acquired EGFR mutation
  • Cohort 7: Documented EGFR or HER2 activating mutations
  • Patient has adequate organ function at Baseline Key

  • Patient has had previous treatment with poziotinib or any other EGFR or HER2 exon 20 insertion mutation-selective tyrosine kinase inhibitor (TKI) prior to study participation. The currently approved TKIs (ie, erlotinib, gefitinib, afatinib, osimertinib) are not considered to be exon 20 insertion-selective and are permissible (Cohorts 1 to 4).
  • Patient is concurrently receiving chemotherapy, biologics, immunotherapy for cancer treatment; systemic anti-cancer treatment or investigational treatment should not be used within 2 weeks; local radiation therapy for bone pain may be allowed
  • Patient has had other malignancies within the past 3 years, except for stable non-melanoma skin cancer, fully treated and stable early stage prostate cancer or carcinoma in situ of the cervix or breast without need of treatment
  • Patient is pregnant or breast-feeding

Sites

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