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

NCT03318939 | Terminated Phase 2 FDA Drug

• 1 other identifier: SPI-POZ-202
• Study Type: interventional
• Target: 648
• Locations: 8 countries
• Sites: 63

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).

Conditions

NSCLC

Keywords

EGFR; HER2; Exon 20 insertion mutation

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Disease Control Rate (DCR)

  24 months

• Duration of Response (DoR)

  24 months

Other Outcomes (1)

• Progression-free Survival (PFS) - Exploratory

  24 months

Study Arms (1)

Poziotinib

EXPERIMENTAL

* 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

Interventions

Poziotinib DRUG

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

Poziotinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Spectrum Pharmaceuticals, Inc: lead

Study Sites (63)

Mayo Clinic Hospital

Phoenix, Arizona, 85054, United States

Location

Oncology Physician's Network Inc./OPN Healthcare

Arcadia, California, 91007, United States

Location

City of Hope

Duarte, California, 91010, United States

Location

UCSD -Moores Cancer Center

La Jolla, California, 92093, United States

Location

Pacific Shores Medical Group

Long Beach, California, 90813, United States

Location

Los Angeles Hematology Oncology Medical Group

Los Angeles, California, 90017, United States

Location

USC/Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

UC Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

Location

UCSF Helen Diller Comprehensive Cancer Center at Mt Zion

San Francisco, California, 94115, United States

Location

UCLA Hematology/Oncology

Santa Monica, California, 90404, United States

Location

The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center

Torrance, California, 90502, United States

Location

Kaiser Permanente Medical Center

Vallejo, California, 94589, United States

Location

Rocky Mountain Cancer Center

Boulder, Colorado, 80303, United States

Location

Yale University, Yale Cancer Center Smilow Cancer Hospital at Yale

New Haven, Connecticut, 06510, United States

Location

Georgetown University Medical Center

Washington D.C., District of Columbia, 20007, United States

Location

Florida Hospital

Orlando, Florida, 32804, United States

Location

H. Lee Moffitt Cancer Center & Research Institute

Tampa, Florida, 33612, United States

Location

The Bond & Steele Clinic, P.A. dba Bond Clinic, P.A.

Winter Haven, Florida, 33881, United States

Location

University Cancer & Blood Center, LLC

Athens, Georgia, 30607, United States

Location

CTCA - Southeastern Regional Medical Center

Newnan, Georgia, 30265, United States

Location

CTCA - Midwestern Regional Medical Center

Zion, Illinois, 60099, United States

Location

Johns Hopkins Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, 21287, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Minnesota Oncology Hematology, P.A.

Minneapolis, Minnesota, 55404, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Hattiesburg Clinic Hematology/Oncology

Hattiesburg, Mississippi, 39401, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

NYU Langone Medical Center

New York, New York, 10016, United States

Location

Weill Cornell Medical College

New York, New York, 10065, United States

Location

North Shore Hematology Oncology Associates P.C. DBA NY Cancer and Blood Specialists

Port Jefferson Station, New York, 11776, United States

Location

Montefiore Einstein Medical Center for Cancer Care

The Bronx, New York, 10461, United States

Location

North Shore Hematology Oncology Associates DBA New York Cancer and Blood Specialists

The Bronx, New York, 10469, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

The Ohio State University

Columbus, Ohio, 43210, United States

Location

Oklahoma Cancer Specialists and Research Institute, LLC

Tulsa, Oklahoma, 74146, United States

Location

CTCA - Eastern Regional Medical Center

Philadelphia, Pennsylvania, 19124, United States

Location

Baptist Cancer Center

Memphis, Tennessee, 38120, United States

Location

Texas Oncology- Austin

Austin, Texas, 78745, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Virginia Cancer Specialists, PC

Fairfax, Virginia, 22031, United States

Location

Seattle Cancer Care Alliance

Seattle, Washington, 98109, United States

Location

Saint Luc University Hospital

Brussels, Belgium

Location

University Hospitals Leuven

Leuven, Belgium

Location

Ambroise Pare University Hospital Center

Mons, Belgium

Location

General Hospital Delta

Roeselare, Belgium

Location

Cross Cancer Institute

Edmonton, Alberta, T6G 1Z2, Canada

Location

BC Cancer - Vancouver

Vancouver, British Columbia, V5Z 4E6, Canada

Location

London Regional Cancer Program

London, Ontario, N6A 5W9, Canada

Location

Princess Margaret Cancer Centre

Toronto, Ontario, M5G 2M9, Canada

Location

Hopital Larrey, CHU Toulouse, Unité d'Oncologie des Voies Respiratoires

Toulouse, France

Location

Gustave Roussy Oncology Institute, Department of Medical Oncology

Villejuif, France

Location

Soroka Medical Center

Beersheba, Israel

Location

Rambam Healthcare Campus

Haifa, Israel

Location

Hadassah Medical Center

Jerusalem, Israel

Location

Rabin Medical Center

Petah Tikva, Israel

Location

National Cancer Institute, IRCCS, Department of Medical Oncology

Milan, Italy

Location

Santa Maria delle Croci Hospital

Ravenna, Italy

Location

National Cancer Institute Regina Elena, IRCCS, Operative Unit of Medical Oncology A 1

Rome, Italy

Location

Erasmus Medical Center

Rotterdam, Netherlands

Location

University Hospital Germans Trias i Pujol, Department of Medical Oncology

Barcelona, Spain

Location

University Hospital 12 de Octubre

Madrid, Spain

Location

Related Publications (1)

• 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.

  PMID: 34843401 DERIVED

MeSH Terms

Interventions

HM781-36B

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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

Study Record Dates

• First Submitted: October 10, 2017
• First Posted: October 24, 2017
• Study Start: October 13, 2017
• Primary Completion: April 3, 2023
• Study Completion: April 3, 2023
• Last Updated: April 3, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (43); CA (4); BE (4); NL (1); IL (4); ES (2); FR (2); IT (3)