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

NSCLC Clinical Trial

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 Details — Status: Terminated

Administrative data

• NCT number: NCT03318939
• Other study ID #: SPI-POZ-202
• Status: Terminated
• Phase: Phase 2
• Start date: October 13, 2017
• Est. completion date: April 3, 2023

Study information

• Verified date: April 2024
• Source: Spectrum Pharmaceuticals, Inc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 648
• Est. completion date: April 3, 2023
• Est. primary completion date: April 3, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• 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

Locations

Country	Name	City	State
Belgium	Saint Luc University Hospital	Brussels
Belgium	University Hospitals Leuven	Leuven
Belgium	Ambroise Pare University Hospital Center	Mons
Belgium	General Hospital Delta	Roeselare
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	London Regional Cancer Program	London	Ontario
Canada	Princess Margaret Cancer Centre	Toronto	Ontario
Canada	BC Cancer - Vancouver	Vancouver	British Columbia
France	Hopital Larrey, CHU Toulouse, Unité d'Oncologie des Voies Respiratoires	Toulouse
France	Gustave Roussy Oncology Institute, Department of Medical Oncology	Villejuif
Israel	Soroka Medical Center	Be'er Sheva
Israel	Rambam Healthcare Campus	Haifa
Israel	Hadassah Medical Center	Jerusalem
Israel	Rabin Medical Center	Petah Tikva
Italy	National Cancer Institute, IRCCS, Department of Medical Oncology	Milan
Italy	Santa Maria delle Croci Hospital	Ravenna
Italy	National Cancer Institute Regina Elena, IRCCS, Operative Unit of Medical Oncology A 1	Rome
Netherlands	Erasmus Medical Center	Rotterdam
Spain	University Hospital Germans Trias i Pujol, Department of Medical Oncology	Barcelona
Spain	University Hospital 12 de Octubre	Madrid
United States	Oncology Physician's Network Inc./OPN Healthcare	Arcadia	California
United States	University Cancer & Blood Center, LLC	Athens	Georgia
United States	Texas Oncology- Austin	Austin	Texas
United States	Johns Hopkins Sidney Kimmel Comprehensive Cancer Center	Baltimore	Maryland
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Rocky Mountain Cancer Center	Boulder	Colorado
United States	Montefiore Einstein Medical Center for Cancer Care	Bronx	New York
United States	North Shore Hematology Oncology Associates DBA New York Cancer and Blood Specialists	Bronx	New York
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Cleveland Clinic	Cleveland	Ohio
United States	The Ohio State University	Columbus	Ohio
United States	Karmanos Cancer Institute	Detroit	Michigan
United States	City of Hope	Duarte	California
United States	Duke University Medical Center	Durham	North Carolina
United States	Virginia Cancer Specialists, PC	Fairfax	Virginia
United States	Hattiesburg Clinic Hematology/Oncology	Hattiesburg	Mississippi
United States	MD Anderson Cancer Center	Houston	Texas
United States	UCSD -Moores Cancer Center	La Jolla	California
United States	Pacific Shores Medical Group	Long Beach	California
United States	Los Angeles Hematology Oncology Medical Group	Los Angeles	California
United States	USC/Norris Comprehensive Cancer Center	Los Angeles	California
United States	Baptist Cancer Center	Memphis	Tennessee
United States	Minnesota Oncology Hematology, P.A.	Minneapolis	Minnesota
United States	Yale University, Yale Cancer Center Smilow Cancer Hospital at Yale	New Haven	Connecticut
United States	NYU Langone Medical Center	New York	New York
United States	Weill Cornell Medical College	New York	New York
United States	CTCA - Southeastern Regional Medical Center	Newnan	Georgia
United States	Florida Hospital	Orlando	Florida
United States	CTCA - Eastern Regional Medical Center	Philadelphia	Pennsylvania
United States	Mayo Clinic Hospital	Phoenix	Arizona
United States	North Shore Hematology Oncology Associates P.C. DBA NY Cancer and Blood Specialists	Port Jefferson Station	New York
United States	Mayo Clinic	Rochester	Minnesota
United States	UC Davis Comprehensive Cancer Center	Sacramento	California
United States	UCSF Helen Diller Comprehensive Cancer Center at Mt Zion	San Francisco	California
United States	UCLA Hematology/Oncology	Santa Monica	California
United States	Seattle Cancer Care Alliance	Seattle	Washington
United States	H. Lee Moffitt Cancer Center & Research Institute	Tampa	Florida
United States	The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center	Torrance	California
United States	Oklahoma Cancer Specialists and Research Institute, LLC	Tulsa	Oklahoma
United States	Kaiser Permanente Medical Center	Vallejo	California
United States	Georgetown University Medical Center	Washington	District of Columbia
United States	The Bond & Steele Clinic, P.A. dba Bond Clinic, P.A.	Winter Haven	Florida
United States	CTCA - Midwestern Regional Medical Center	Zion	Illinois

Sponsors (1)

Lead Sponsor	Collaborator
Spectrum Pharmaceuticals, Inc

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  France,  Israel,  Italy,  Netherlands,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Progression-free Survival (PFS) - Exploratory	Number of days from the treatment start date to the date of documented disease progression or death due to any cause.	24 months
Primary	Objective Response Rate (ORR)	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.	24 months
Secondary	Disease Control Rate (DCR)	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.	24 months
Secondary	Duration of Response (DoR)	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.	24 months