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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03318939
Recruitment Status : Active, not recruiting
First Posted : October 24, 2017
Last Update Posted : January 31, 2023
Sponsor:
Information provided by (Responsible Party):
Spectrum Pharmaceuticals, Inc

Tracking Information
First Submitted Date  ICMJE October 10, 2017
First Posted Date  ICMJE October 24, 2017
Last Update Posted Date January 31, 2023
Actual Study Start Date  ICMJE October 13, 2017
Estimated Primary Completion Date March 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 20, 2017)
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 20, 2017)
  • 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.
  • 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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: October 20, 2017)
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.
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Phase 2 Study of Poziotinib in Patients With NSCLC Having EGFR or HER2 Exon 20 Insertion Mutation
Official Title  ICMJE 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)
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).
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE 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
Condition  ICMJE NSCLC
Intervention  ICMJE 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
Study Arms  ICMJE 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
Intervention: Drug: Poziotinib
Publications * Le X, Cornelissen R, Garassino M, Clarke JM, Tchekmedyian N, Goldman JW, Leu SY, Bhat G, Lebel F, Heymach JV, Socinski MA. Poziotinib in Non-Small-Cell Lung Cancer Harboring HER2 Exon 20 Insertion Mutations After Prior Therapies: ZENITH20-2 Trial. J Clin Oncol. 2022 Mar 1;40(7):710-718. doi: 10.1200/JCO.21.01323. Epub 2021 Nov 29.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: April 24, 2020)
603
Original Estimated Enrollment  ICMJE
 (submitted: October 20, 2017)
174
Estimated Study Completion Date  ICMJE December 30, 2023
Estimated Primary Completion Date March 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Belgium,   Canada,   France,   Israel,   Italy,   Netherlands,   Spain,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03318939
Other Study ID Numbers  ICMJE SPI-POZ-202
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party Spectrum Pharmaceuticals, Inc
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Spectrum Pharmaceuticals, Inc
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Spectrum Pharmaceuticals, Inc
Verification Date January 2023

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP