Phase 2 Study of Poziotinib in Participants With NSCLC Having EGFR or HER2 Exon 20 Insertion Mutation
- Registration Number
- NCT03318939
- Lead Sponsor
- Spectrum Pharmaceuticals, Inc
- 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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 648
-
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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Poziotinib 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
- Primary Outcome Measures
Name Time Method Objective Response Rate (ORR) 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
Name Time Method Disease Control Rate (DCR) 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) 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.
Trial Locations
- Locations (63)
UCLA Hematology/Oncology
🇺🇸Santa Monica, California, United States
Kaiser Permanente Medical Center
🇺🇸Vallejo, California, United States
Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
🇺🇸Baltimore, Maryland, United States
Hattiesburg Clinic Hematology/Oncology
🇺🇸Hattiesburg, Mississippi, United States
The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
🇺🇸Torrance, California, United States
Los Angeles Hematology Oncology Medical Group
🇺🇸Los Angeles, California, United States
CTCA - Eastern Regional Medical Center
🇺🇸Philadelphia, Pennsylvania, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
The Ohio State University
🇺🇸Columbus, Ohio, United States
MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Seattle Cancer Care Alliance
🇺🇸Seattle, Washington, United States
Minnesota Oncology Hematology, P.A.
🇺🇸Minneapolis, Minnesota, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
NYU Langone Medical Center
🇺🇸New York, New York, United States
Georgetown University Medical Center
🇺🇸Washington, District of Columbia, United States
Baptist Cancer Center
🇺🇸Memphis, Tennessee, United States
Rambam Healthcare Campus
🇮🇱Haifa, Israel
Hadassah Medical Center
🇮🇱Jerusalem, Israel
Cross Cancer Institute
🇨🇦Edmonton, Alberta, Canada
General Hospital Delta
🇧🇪Roeselare, Belgium
BC Cancer - Vancouver
🇨🇦Vancouver, British Columbia, Canada
Saint Luc University Hospital
🇧🇪Brussels, Belgium
Ambroise Pare University Hospital Center
🇧🇪Mons, Belgium
Weill Cornell Medical College
🇺🇸New York, New York, United States
Mayo Clinic Hospital
🇺🇸Phoenix, Arizona, United States
UCSF Helen Diller Comprehensive Cancer Center at Mt Zion
🇺🇸San Francisco, California, United States
Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
UC Davis Comprehensive Cancer Center
🇺🇸Sacramento, California, United States
Yale University, Yale Cancer Center Smilow Cancer Hospital at Yale
🇺🇸New Haven, Connecticut, United States
Florida Hospital
🇺🇸Orlando, Florida, United States
H. Lee Moffitt Cancer Center & Research Institute
🇺🇸Tampa, Florida, United States
USC/Norris Comprehensive Cancer Center
🇺🇸Los Angeles, California, United States
Oncology Physician's Network Inc./OPN Healthcare
🇺🇸Arcadia, California, United States
City of Hope
🇺🇸Duarte, California, United States
UCSD -Moores Cancer Center
🇺🇸La Jolla, California, United States
Rocky Mountain Cancer Center
🇺🇸Boulder, Colorado, United States
The Bond & Steele Clinic, P.A. dba Bond Clinic, P.A.
🇺🇸Winter Haven, Florida, United States
CTCA - Southeastern Regional Medical Center
🇺🇸Newnan, Georgia, United States
University Cancer & Blood Center, LLC
🇺🇸Athens, Georgia, United States
CTCA - Midwestern Regional Medical Center
🇺🇸Zion, Illinois, United States
North Shore Hematology Oncology Associates DBA New York Cancer and Blood Specialists
🇺🇸Bronx, New York, United States
Montefiore Einstein Medical Center for Cancer Care
🇺🇸Bronx, New York, United States
Roswell Park Cancer Institute
🇺🇸Buffalo, New York, United States
North Shore Hematology Oncology Associates P.C. DBA NY Cancer and Blood Specialists
🇺🇸Port Jefferson Station, New York, United States
Cleveland Clinic
🇺🇸Cleveland, Ohio, United States
Oklahoma Cancer Specialists and Research Institute, LLC
🇺🇸Tulsa, Oklahoma, United States
Texas Oncology- Austin
🇺🇸Austin, Texas, United States
Virginia Cancer Specialists, PC
🇺🇸Fairfax, Virginia, United States
University Hospitals Leuven
🇧🇪Leuven, Belgium
Gustave Roussy Oncology Institute, Department of Medical Oncology
🇫🇷Villejuif, France
London Regional Cancer Program
🇨🇦London, Ontario, Canada
Princess Margaret Cancer Centre
🇨🇦Toronto, Ontario, Canada
Hopital Larrey, CHU Toulouse, Unité d'Oncologie des Voies Respiratoires
🇫🇷Toulouse, France
National Cancer Institute, IRCCS, Department of Medical Oncology
🇮🇹Milan, Italy
Soroka Medical Center
🇮🇱Be'er Sheva, Israel
Rabin Medical Center
🇮🇱Petah Tikva, Israel
Santa Maria delle Croci Hospital
🇮🇹Ravenna, Italy
National Cancer Institute Regina Elena, IRCCS, Operative Unit of Medical Oncology A 1
🇮🇹Rome, Italy
Erasmus Medical Center
🇳🇱Rotterdam, Netherlands
University Hospital Germans Trias i Pujol, Department of Medical Oncology
🇪🇸Barcelona, Spain
University Hospital 12 de Octubre
🇪🇸Madrid, Spain
Pacific Shores Medical Group
🇺🇸Long Beach, California, United States