Phase 2 Study of Poziotinib in Patients With NSCLC Having EGFR or HER2 Exon 20 Insertion Mutation

Official Title

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)

Summary:

This is a Phase 2, open-label, multi-centre study to evaluate the efficacy and the safety/tolerability of poziotinib in seven patient cohorts for up to 603 previously treated and treatment-naïve NSCLC patients. Cohorts 3 and 4 were added with Amendment 1 and three additional cohorts were added with Amendment 2 (Cohorts 5, 6 and 7).

Trial Description

Primary Outcome:

• Objective Response Rate (ORR)

Secondary Outcome:

• Disease Control Rate (DCR)
• Duration of Response (DoR)

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 (fully enrolled)

• 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. 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 until disease progression (except for first progression in Cohort 5), death, intolerable adverse events (AEs), or other protocol-specified reasons for patient withdrawal.

View this trial on ClinicalTrials.gov