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

• ClinicalTrials.gov Identifier: NCT03318939
• Recruitment Status: Terminated
• First Posted: October 24, 2017
• Last Update Posted: April 3, 2024
• Sponsor: Spectrum Pharmaceuticals, Inc
• Information provided by (Responsible Party): Spectrum Pharmaceuticals, Inc

Tracking Information

• First Submitted Date: October 10, 2017
• First Posted Date: October 24, 2017
• Last Update Posted Date: April 3, 2024
• Actual Study Start Date: October 13, 2017
• Actual Primary Completion Date: April 3, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (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: Same as current

Current Secondary Outcome Measures (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: 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: Phase 2 Study of Poziotinib in Participants 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)
• 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).

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 Type: Interventional
• Study Phase: Phase 2

Study Design

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

• Condition: NSCLC

Intervention

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

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

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.

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: January 24, 2024): 648
• Original Estimated Enrollment (submitted: October 20, 2017): 174
• Actual Study Completion Date: April 3, 2023
• Actual Primary Completion Date: April 3, 2023 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Belgium, Canada, France, Israel, Italy, Netherlands, Spain, United States

Administrative Information

• NCT Number: NCT03318939
• Other Study ID Numbers: 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

• Plan to Share IPD: No

• Current Responsible Party: Spectrum Pharmaceuticals, Inc
• Original Responsible Party: Same as current
• Current Study Sponsor: Spectrum Pharmaceuticals, Inc
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Spectrum Pharmaceuticals, Inc
• Verification Date: April 2024