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) (SPI-POZ-202)
Johns Hopkins Kimmel Cancer Center in Baltimore
Sibley Memorial Hospital
Johns Hopkins Bayview Medical Center
Objectives:Primary Objective:• To evaluate the Objective Response Rate (ORR) to poziotinib in patients with non-small cell lung cancer (NSCLC) with EGFR or HER2 (ErBB2) exon 20 insertion mutationsSecondary Objectives:• To evaluate other efficacy variables of poziotinib in patients with NSCLC with EGFR or HER2 exon 20 insertion mutations, including the following: 1. Disease Control Rate (DCR) (complete response + partial response + stable disease) 2. Duration of Response (DoR)• To evaluate the safety and tolerability of poziotinib in patients with NSCLC with EGFR or HER2 exon 20 insertion mutationsExploratory Objectives:• To evaluate Progression-free Survival (PFS) in patients with NSCLC with EGFR or HER2 exon 20 insertion mutations who are treated with poziotinib• To evaluate the Quality of Life, before and after treatment, in patients with NSCLC with EGFR or HER2 exon 20 insertion mutations who are treated with poziotinib
Patient has histologically or cytologically confirmed non-small cell lung cancer not amenable to curative intent therapy or stage IV NSCLC Specific mutations:• Cohort 1: Documented EGFR exon 20 insertion mutation using an FDA-approved in vitro diagnostic test (ie, cobas® EGFR mutation test v2 or therascreen EGFR RGQ PCR kit), a CLIA certified test (for US sites) (eg, OncoMine Comprehensive Assay (OCA), Guardant360 Assay (using plasma), or FoundationOne Assay), or similarly accredited test (for ex-US sites) for tissue or plasma• Cohort 2: Documented HER2 exon 20 insertion mutation using a CLIA certified test (for US sites) (eg, OncoMine Comprehensive Assay (OCA), Guardant360 Assay (using plasma), or FoundationOne Assay) or similarly accredited test (for ex-US sites) for tissue or plasma
This is a Phase 2, open-label, multicenter study to evaluate the efficacy and the safety/tolerability of poziotinib in up to 174 patients with NSCLC exon 20 insertion mutations (87 patients with EGFR exon 20 insertion mutations and 87 patients with HER2 exon 20 insertion mutations).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 two cohorts and eligible patients will be enrolled into each cohort based on EGFR or HER2 exon 20 mutant status:• Cohort 1: Patients with EGFR exon 20 insertion-mutant non-small cell lung cancer (NSCLC)• Cohort 2: Patients with HER2 exon 20 insertion-mutant non-small cell lung cancer (NSCLC)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 equal to 1.5×109/L and platelet count must be equal to 100×109/L before administering poziotinib. All patients will be treated until disease progression, death, intolerable adverse events, or up to a maximum of 24 months, whichever comes first.
03/05/2019 05:03 AM