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

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ClinicalTrials.gov Identifier: NCT03318939
Recruitment Status : Terminated (Strategic business decision (unrelated to safety))
First Posted : October 24, 2017
Last Update Posted : April 3, 2024
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 participant cohorts for up to 603 previously treated and treatment-naïve NSCLC participant. 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. Participant must meet all Inclusion/Exclusion Criteria to participate in the study. Eligible participants will provide written Informed Consent prior to undergoing any study procedures.

Each treatment cycle is 28 calendar days in duration. There will be seven participant cohorts and eligible participants 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 participant with EGFR exon 20 insertion mutation positive NSCLC (complete)
  • Cohort 2: Previously treated participant with HER2 exon 20 insertion mutation positive NSCLC (complete)
  • Cohort 3: Treatment naïve participant with EGFR exon 20 insertion mutation positive NSCLC (complete)
  • Cohort 4: Treatment naïve participant with HER2 exon 20 insertion mutation positive NSCLC (fully enrolled)
  • Cohort 5: Participants who meet the criteria for enrollment in Cohort 1 to 4, but the enrollment in the respective cohort has been closed (closed to enrollment)
  • Cohort 6: Participants with acquired EGFR mutation who progressed while on treatment with first-line osimertinib (closed to enrollment)
  • Cohort 7: Participants with EGFR or HER2 activating mutations (closed to enrollment)

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 participant'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 participants will be treated until disease progression (except for first progression in Cohort 5), death, intolerable adverse events (AEs), or other protocol-specified reasons for participant withdrawal.

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 648 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 participant cohorts and eligible participants 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 participants with EGFR exon 20 insertion mutant positive NSCLC (closed to enrollment)
  • Cohort 2: Previously treated participants with HER2 exon 20 insertion mutant positive NSCLC (closed to enrollment)
  • Cohort 3: Treatment naïve participants with EGFR exon 20 insertion mutant positive NSCLC (fully enrolled)
  • Cohort 4: Treatment naïve participants with HER2 exon 20 insertion mutant positive NSCLC
  • Cohort 5: Participants who meet the criteria for enrollment in Cohort 1 to 4, but the enrollment in the respective cohort has been closed
  • Cohort 6: Participants with acquired EGFR mutation who progressed while on treatment with first-line osimertinib
  • Cohort 7: Participants 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
Actual Primary Completion Date : April 3, 2023
Actual Study Completion Date : April 3, 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 participants with EGFR exon 20 insertion mutant positive NSCLC (closed to enrollment)
  • Cohort 2: Previously treated participants with HER2 exon 20 insertion mutant positive NSCLC (closed to enrollment)
  • Cohort 3: Treatment naïve participants with EGFR exon 20 insertion-mutant positive NSCLC (fully enrolled)
  • Cohort 4: Treatment naïve participants with HER2 exon 20 insertion mutant positive NSCLC
  • Cohort 5: Participants who meet the criteria for enrollment in Cohort 1 to 4, but the enrollment in the respective cohort has been closed
  • Cohort 6: Participants with acquired EGFR mutation who progressed while on treatment with first-line osimertinib
  • Cohort 7: Participants 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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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:

  • Participant must be willing and capable of giving written Informed Consent, adhering to dosing and visit schedules, and meeting all study requirements
  • Participant 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: Participant has had at least one prior systemic treatment for locally advanced or metastatic NSCLC
    • Cohorts 3 and 4: Participant 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: Participants who meet the criteria for enrollment in Cohorts 1 to 4, but the enrollment in the respective cohort has been closed
    • Cohort 6: Participant with EGFR mutation-positive NSCLC who progressed while on treatment with first-line osimertinib
    • Cohort 7: Participant 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
  • Participant has adequate organ function at Baseline

Key Exclusion Criteria:

  • Participant 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).
  • Participant 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
  • Participant 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
  • Participant 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


Locations
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Sponsors and Collaborators
Spectrum Pharmaceuticals, Inc
More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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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: April 3, 2024
Last Verified: April 2024
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