Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Carcinoma, Non-Small-Cell Lung

Carcinoma

Lung Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

All Drugs and Chemicals

Antineoplastic Agents

Antibodies

Antibodies, Monoclonal

Vaccines

Immunoglobulins

Ramucirumab

Lexatumumab

Patients receive poziotinib hydrochloride PO BID on day 1 and ramucirumab IV over 30-60 minutes on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

1429757-68-5, HM781-36B, NOV-1201 Hydrochloride, NOV120101 Hydrochloride, Poziotinib HCl, POZIOTINIB HYDROCHLORIDE

Given PO

Poziotinib Hydrochloride

Biological/Vaccine Ramucirumab 947687-13-0, anti-VEGFR-2 fully human monoclonal antibody IMC-1121B, Anti-VEGFR-2 Fully Human Monoclonal Antibody IMC-1121B, Cyramza, IMC-1121B, IMC-1121B, LY3009806, Monoclonal Antibody HGS-ETR2, ramucirumab, RAMUCIRUMAB

Given IV

1429757-68-5, HM781-36B, NOV-1201 Hydrochloride, NOV120101 Hydrochloride, Poziotinib HCl, POZIOTINIB HYDROCHLORIDE

Yasir Elamin, MD

This phase II trial tests whether poziotinib and ramucirumab work to shrink tumors in patients with EGFR Exon 20 gene mutant stage IV non-small cell lung cancer. Poziotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Ramucirumab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. Giving poziotinib and ramucirumab may help to control the disease.

PRIMARY OBJECTIVE:

I. To evaluate the efficacy of the combination of poziotinib and ramucirumab as measured by progression free survival.

SECONDARY OBJECTIVES:

I. To estimate the objective response rate per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 for the combination of poziotinib and ramucirumab.

II. To estimate the disease control rate (complete response + partial response + stable disease), overall survival, and duration of response of the study combination.

III. To assess the safety and the toxicity of the study combination.

EXPLORATORY OBJECTIVE:

I. To assess molecular markers associated with resistance and response to poziotinib and ramucirumab.

OUTLINE:

Patients receive poziotinib hydrochloride orally (PO) twice daily (BID) on day 1 and ramucirumab intravenously (IV) over 30-60 minutes on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed at 30 days, then every 6 months thereafter.

Poziotinib and Ramucirumab for the Treatment of EGFR Exon 20 Mutant Stage IV Non-small Cell Lung Cancer

A Phase II Study of Poziotinib and Ramucirumab in EGFR Exon 20 Mutant Advanced Non-small Cell Lung Cancer (NSCLC)

Estimated using the Kaplan and Meier method.

M.D. Anderson Cancer Center

Skin and Connective Tissue Diseases

Breast Neoplasms

Breast Diseases

Skin Diseases

Gastrointestinal Agents

Loperamide

Mitogens

Antidiarrheals

Patients with HER2-positive or HER2-negative BC with a HER2 activating mutation will receive poziotinib 8 milligrams (mg), orally, twice daily (BID) starting on Day 1 of each 28 day cycle for up to 24 months unless there is disease progression, death, intolerable AEs, or another protocol-specified reason for participant withdrawal. Loperamide may be prescribed for the treatment of diarrhea as needed.

Patients with CRC with a HER2 activating mutation will receive poziotinib 8 mg, orally, BID starting on Day 1 of each 28 day cycle for up to 24 months unless there is disease progression, death, intolerable AEs, or another protocol-specified reason for participant withdrawal. Loperamide may be prescribed for the treatment of diarrhea as needed.

The poziotinib drug substance is a hydrochloride salt of poziotinib and is formulated as a tablet for oral administration.

Loperamide as prescribed by the physician.

Jaba Kokhreidze, MD

This is a Phase 2, open-label, multicenter study whose principal objectives are to evaluate the efficacy and safety/tolerability of poziotinib in five cohorts of 30 previously-treated patients each.

The Screening period (Day -30 to Day 1) begins 30 days prior to poziotinib treatment on Day 1 of Cycle 1. Patients must meet all Inclusion/Exclusion Criteria and provide informed written consent prior to study procedures.

The duration of each treatment cycle is 28 days. There will be five patient cohorts. Eligible patients will be enrolled into cohorts concurrently based on EGFR or HER2 exon 20 mutation status.

* Cohort 1: HER2-positive or HER2-negative breast cancer (BC) with a HER2 activating mutation.
* Cohort 2: Colorectal cancer (CRC) with a HER2 activating mutation.
* Cohort 3: Any solid cancer, except non-small cell lung cancer (NSCLC), BC, or CRC with a HER2 activating mutation.
* Cohort 4: Glioblastome multiforma (GBM) with an EGFR activating mutation.
* Cohort 5: Any solid cancer, except NSCLC or GBM with an EGFR activating mutation.

All patients will be treated daily for up to 24 months unless there is disease progression, death, intolerable adverse events (AEs), or another protocol-specified reason for patient withdrawal. After treatment discontinuation, patients will be contacted every 3 months for up to 2 years after the first dose of poziotinib to assess survival.

Each treatment cycle is 28 calendar days in duration. This is a basket study with five distinct cohorts. Eligible patients will be enrolled into the five cohorts concurrently based on tumor type and mutational status.

A Study of Poziotinib in Patients With Epidermal Growth Factor Receptor (EGFR) or Human Epidermal Growth Factor Receptor 2 (HER2) Activating Mutations in Advanced Malignancies

A Phase 2 Study of Poziotinib in Patients With EGFR or HER2 Activating Mutations in Advanced Malignancies

ORR was defined as the percentage of participants with confirmed complete response (CR) and partial response (PR) as assessed by the investigator using local radiology evaluation according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1). CR is defined as the disappearance of all target and non-target lesions. Any pathological lymph nodes must have a reduction in the short axis to \<10 millimeters (mm). PR is defined as at least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR.

Duration of response was defined as the time from the date that measurement criteria are first met for CR or PR until the first subsequent date that progressive disease or death is documented. CR is defined as the disappearance of all target and non-target lesions. Any pathological lymph nodes must have a reduction in the short axis to \<10 mm. PR is defined as at least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. Disease progression (PD) is defined as ≥20% increase in the sum of diameters of target lesions, unequivocal progression in non-target lesions, and/or appearance of new lesions.

DCR is defined as percentage of participants with best response of CR, PR, and stable disease (SD) from the first dose of poziotinib to the end of study. CR is defined as disappearance of all target and non-target lesions. Any pathological lymph nodes must have reduction in short axis to \<10 mm. PR is defined as at least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of the longest diameter (LD) since the treatment started.

An AE is defined as any untoward medical occurrence in a patient or clinical investigation patient, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Therefore, an AE can be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product.

Spectrum Pharmaceuticals, Inc

The Safety Analysis Population included all enrolled patients who received at least 1 dose of poziotinib. As the study was terminated early by the sponsor, there were no participants enrolled in cohorts 1-4.

Participants with HER2 positive or HER2-negative breast cancer (BC) with a HER2 activating mutation were to receive poziotinib 8 mg, orally, BID starting on Day 1 of each 28-day cycle for up to 24 months unless there is disease progression, death, intolerable adverse events AEs, or another protocol-specified reason for participant withdrawal. Participants were also to receive loperamide 4 mg two to three times a day according to treating physician's instructions.

Cohort 1

Participants with CRC with a HER2 activating mutation were to receive poziotinib 8 mg, orally, BID starting on Day 1 of each 28-day cycle for up to 24 months unless there is disease progression, death, intolerable AEs, or another protocol-specified reason for participant withdrawal. Participants were also to receive loperamide 4 mg two to three times a day or according to the treating physician's instructions.

Cohort 2

Participants with solid tumors (except NSCLC, BC, or CRC) with a HER2 activating mutation were to receive poziotinib 8 mg, orally, BID starting on Day 1 of each 28-day cycle for up to 24 months unless there is disease progression, death, intolerable AEs, or another protocol-specified reason for participant withdrawal. Participants were also to receive loperamide 4 mg two to three times a day or according to the treating physician's instructions.

Cohort 3

Participants with GBM with EGFR activating mutation were to receive poziotinib 8 mg, orally, BID starting on Day 1 of each 28-day cycle for up to 24 months unless there is disease progression, death, intolerable AEs, or another protocol-specified reason for participant withdrawal. Participants were also to receive loperamide 4 mg two to three times a day or according to the treating physician's instructions.

Cohort 4

Participants with solid tumors (except NSCLC or GBM) with EGFR activating mutations were to receive poziotinib 8 mg, orally, BID starting on Day 1 of each 28-day cycle for up to 24 months unless there is disease progression, death, intolerable AEs, or another protocol-specified reason for participant withdrawal. Participants were also to receive loperamide 4 mg two to three times a day or according to the treating physician's instructions.

Cohort 5

Participants with HER2-positive or HER2-negative BC with a HER2 activating mutation were to receive poziotinib 8 mg, orally, BID starting on Day 1 of each 28-day cycle for up to 24 months unless there is disease progression, death, intolerable AEs, or another protocol-specified reason for participant withdrawal. Participants were also to receive loperamide 4 mg two to three times a day according to the treating physician's instructions.

Total

The study was terminated by the Sponsor. Based on the low enrollment number (n=1), no data is reported here to protect and maintain participant privacy/confidentiality.

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Howard Franklin, MD

Participants with HER2 positive or HER2-negative BC with a HER2 activating mutation were to receive poziotinib 8 mg, orally, BID starting on Day 1 of each 28-day cycle for up to 24 months unless there is disease progression, death, intolerable AEs, or another protocol-specified reason for participant withdrawal. Participants were also to receive loperamide 4 mg two to three times a day according to treating physician's instructions.

Participants with solid tumors (except NSCLC, BC, or CRC) with a HER2 activating mutation were to receive poziotinib 8 mg, orally, BID starting on Day 1 of each 28-day cycle for up to 24 months unless there is disease progression, death, intolerable AEs, or another protocol-specified reason for participant withdrawal. Participants were also to receive loperamide 4 mg two to three times a day or according to the treating physician's instructions

Participants with GBM with EGFR activating mutation were to receive poziotinib 8 mg, orally, BID starting on Day 1 of each 28-day cycle for up to 24 months unless there is disease progression, death, intolerable AEs, or another protocol-specified reason for participant withdrawal. Participants were also to receive loperamide 4 mg two to three times a day or according to the treating physician's instructions

The Evaluable Population included all enrolled participants who completed at least 6 weeks of poziotinib treatment, had baseline and at least 1 post-baseline tumor response evaluation using RECIST, v1.1, or progressed prior to any post-baseline image evaluation. As the study was terminated early by the sponsor, there were no participants enrolled in cohorts 1-4.

Objective Response Rate (ORR)

Participants with HER2-positive or HER2-negative BC with a HER2 activating mutation were to receive poziotinib 8 mg, orally, BID starting on Day 1 of each 28-day cycle for up to 24 months unless there is disease progression, death, intolerable AEs, or another protocol-specified reason for participant withdrawal. Participants were also to receive loperamide 4 mg two to three times a day according to treating physician's instructions.

The Evaluable Population included all enrolled participants who completed at least 6 weeks of poziotinib treatment, had baseline and at least 1 post-baseline tumor response evaluation using RECIST, v1.1 or progressed prior to any post-baseline image evaluation. As the study was terminated early by the sponsor, there were no participants enrolled in cohorts 1-4.

Duration of Response (DoR)

Disease Control Rate (DCR)

Participants with solid tumors (except non-small cell lung cancer (NSCLC), BC, or CRC) with a HER2 activating mutation were to receive poziotinib 8 mg, orally, BID starting on Day 1 of each 28-day cycle for up to 24 months unless there is disease progression, death, intolerable AEs, or another protocol-specified reason for participant withdrawal. Participants were also to receive loperamide 4 mg two to three times a day or according to the treating physician's instructions.

Percentage of Participants With AE

Participants with human epidermal growth factor receptor 2 (HER2) positive or HER2-negative breast cancer (BC) with a HER2 activating mutation were to receive poziotinib 8 milligrams (mg), orally, twice daily (BID) starting on Day 1 of each 28-day cycle for up to 24 months unless there is disease progression, death, intolerable adverse events (AEs), or another protocol-specified reason for participant withdrawal. Participants were also to receive loperamide 4 mg two to three times a day according to treating physician's instructions.

Participants with colorectal cancer (CRC) with a HER2 activating mutation were to receive poziotinib 8 mg, orally, BID starting on Day 1 of each 28-day cycle for up to 24 months unless there is disease progression, death, intolerable AEs, or another protocol-specified reason for participant withdrawal. Participants were also to receive loperamide 4 mg two to three times a day or according to the treating physician's instructions.

Participants with glioblastoma (GBM) with epidermal growth factor receptor (EGFR) activating mutation were to receive poziotinib 8 mg, orally, BID starting on Day 1 of each 28-day cycle for up to 24 months unless there is disease progression, death, intolerable AEs, or another protocol-specified reason for participant withdrawal. Participants were also to receive loperamide 4 mg two to three times a day or according to the treating physician's instructions.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Poziotinib and Ramucirumab for the Treatment of EGFR Exon 20 Mutant Stage IV Non-small Cell Lung Cancer	NCT05045404	Metastatic Lung... Stage IV Lung C... Stage IVA Lung ... Stage IVB Lung ...	Poziotinib Hydr... 1429757-68-5, H...	18 Years -	M.D. Anderson Cancer Center
A Study of Poziotinib in Patients With Epidermal Growth Factor Receptor (EGFR) or Human Epidermal Growth Factor Receptor 2 (HER2) Activating Mutations in Advanced Malignancies	NCT04172597	Breast Cancer Colorectal Canc... Solid Tumor Glioblastome Mu...	Poziotinib Hydr... Loperamide	18 Years -	Spectrum Pharmaceuticals, Inc
Poziotinib and Ramucirumab for the Treatment of EGFR Exon 20 Mutant Stage IV Non-small Cell Lung Cancer	NCT05045404	Metastatic Lung... Stage IV Lung C... Stage IVA Lung ... Stage IVB Lung ...	Poziotinib Hydr... 1429757-68-5, H...	18 Years -	M.D. Anderson Cancer Center
Poziotinib and Ramucirumab for the Treatment of EGFR Exon 20 Mutant Stage IV Non-small Cell Lung Cancer	NCT05045404	Metastatic Lung... Stage IV Lung C... Stage IVA Lung ... Stage IVB Lung ...	Poziotinib Hydr... 1429757-68-5, H...	18 Years -	M.D. Anderson Cancer Center
Poziotinib and Ramucirumab for the Treatment of EGFR Exon 20 Mutant Stage IV Non-small Cell Lung Cancer	NCT05045404	Metastatic Lung... Stage IV Lung C... Stage IVA Lung ... Stage IVB Lung ...	Poziotinib Hydr... 1429757-68-5, H...	18 Years -	M.D. Anderson Cancer Center

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