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, multi-center 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).

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 (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.
    

Trial Arms

NameTypeDescriptionInterventions
PoziotinibExperimentalCohort 1: Previously treated patients with EGFR exon 20 insertion mutant positive NSCLC (closed to enrollment) Cohort 2: Previously treated patients with HER2 exon 20 insertion mutant positive NSCLC (closed to enrollment) 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 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
  • 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.

               -  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 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
             (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
      
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

Last Updated

July 23, 2019