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

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ClinicalTrials.gov Identifier: NCT03318939
Recruitment Status : Recruiting
First Posted : October 24, 2017
Last Update Posted : September 16, 2020
Sponsor:
Information provided by (Responsible Party):
Spectrum Pharmaceuticals, Inc

Study Description
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Brief Summary:
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).

Condition or disease Intervention/treatment Phase
NSCLC Drug: Poziotinib Phase 2

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 (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.

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 603 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:

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 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 naïve patients with EGFR exon 20 insertion mutant positive NSCLC (fully enrolled)
  • Cohort 4: Treatment naïve 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
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Actual Study Start Date : October 13, 2017
Estimated Primary Completion Date : March 2023
Estimated Study Completion Date : December 30, 2023

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Poziotinib
  • Cohort 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 naïve patients with EGFR exon 20 insertion-mutant positive NSCLC (fully enrolled)
  • Cohort 4: Treatment naïve 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
 Drug: Poziotinib

The poziotinib drug substance is a hydrochloride salt of poziotinib and is formulated as a tablet for oral administration.

  • Cohorts 1-3: 16 mg QD
  • Cohort 4: 8 mg BID
  • Cohort 5: randomized to 8 mg BID or 6 mg BID or 10 mg QD
  • Cohorts 6 and 7: 8 mg BID


Outcome Measures
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Primary Outcome Measures :
  1. Objective Response Rate (ORR) [ Time Frame: 24 months ]
    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 :
  1. Disease Control Rate (DCR) [ Time Frame: 24 months ]
    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.

  2. Duration of Response (DoR) [ Time Frame: 24 months ]
    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.


Other Outcome Measures:
  1. Progression-free Survival (PFS) - Exploratory [ Time Frame: 24 months ]
    Number of days from the treatment start date to the date of documented disease progression or death due to any cause.


Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 Cohorts 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 (tested after osimertinib progression)
    • 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 and 2).
  • Patient is concurrently receiving chemotherapy, biologics, immunotherapy for cancer treatment; systemic anti-cancer treatment or investigational treatment should not be used within 2 weeks or 5 half lives, whichever is longer; 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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03318939


Contacts
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Contact: Lyndah Dreiling, MD 949-788-6700 spi-poz-202@sppirx.com
Contact: Helen Vu spi-poz-202@sppirx.com

Locations
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Sponsors and Collaborators
Spectrum Pharmaceuticals, Inc
Investigators
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Study Director: Lyndah Dreiling, MD Spectrum Pharmaceuticals, Inc
More Information
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Responsible Party: Spectrum Pharmaceuticals, Inc
ClinicalTrials.gov Identifier: NCT03318939    
Other Study ID Numbers: SPI-POZ-202
First Posted: October 24, 2017    Key Record Dates
Last Update Posted: September 16, 2020
Last Verified: September 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Spectrum Pharmaceuticals, Inc:
EGFR
HER2
Exon 20 insertion mutation
Additional relevant MeSH terms:
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Carcinoma, Non-Small-Cell Lung
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
 Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases