Clinical Trials /

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

NCT03318939

Description:

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 (87 patients with EGFR exon 20 insertion mutations and 87 patients with HER2 exon 20 insertion mutations) and up to 140 treatment-naive NSCLC patients (70 patients with EGFR exon 20 insertion mutations and 70 patients with HER2 exon 20 insertion mutations).

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: 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)

Clinical Trial IDs

  • ORG STUDY ID: SPI-POZ-202
  • NCT ID: NCT03318939

Conditions

  • NSCLC

Interventions

DrugSynonymsArms
PoziotinibPoziotinib

Purpose

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 (87 patients with EGFR exon 20 insertion mutations and 87 patients with HER2 exon 20 insertion mutations) and up to 140 treatment-naive NSCLC patients (70 patients with EGFR exon 20 insertion mutations and 70 patients with HER2 exon 20 insertion mutations).

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 four 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

        -  Cohort 2: Previously treated patients with HER2 exon 20 insertion mutation positive
           NSCLC

        -  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

      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 until disease progression, death, intolerable adverse events, or
      other protocol-specified reasons for patient withdrawal.
    

Trial Arms

NameTypeDescriptionInterventions
PoziotinibExperimentalCohort 1: Previously treated patients with EGFR exon 20 insertion mutant positive NSCLC Cohort 2: Previously treated patients with HER2 exon 20 insertion mutant positive NSCLC Cohort 3: Treatment naive patients with EGFR exon 20 insertion-mutant positive NSCLC Cohort 4: Treatment naive patients with HER2 exon 20 insertion mutant positive NSCLC
  • Poziotinib

Eligibility Criteria

        Key Inclusion 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.

          -  Specific mutations:

               -  Cohort 1 and 3: Documented EGFR exon 20 insertion mutation

               -  Cohort 2 and 4: Documented HER2 exon 20 insertion mutation

          -  Patient has adequate organ function at Baseline

        Key Exclusion Criteria:

          -  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.

          -  Patient has had radiotherapy (intention for cure) or surgery (other than surgical
             placement for vascular access and minimally invasive procedures including some biopsy
             procedures) within 2 weeks prior to start of study treatment with poziotinib

          -  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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective Response Rate (ORR)
Time Frame:24 months
Safety Issue:
Description:The proportion of subjects who achieve Complete Response (CR) and Partial Response (PR) by the best response from the first dose of poziotinib to the end of study.

Secondary Outcome Measures

Measure:Disease Control Rate (DCR)
Time Frame:24 months
Safety Issue:
Description:The proportion of subjects who achieve CR, PR, and Stable Disease (SD) by the best response from the first dose of poziotinib to the end of study.
Measure:Duration of Response (DoR)
Time Frame:24 months
Safety Issue:
Description:Number of days from the date that measurement criteria are first met for CR or PR (whichever status is recorded first) until the first subsequent date that progressive disease or death is documented.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Spectrum Pharmaceuticals, Inc

Trial Keywords

  • EGFR
  • HER2
  • Exon 20 insertion mutation

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