Study of Poziotinib in Participants With HER2-Positive Metastatic Breast Cancer

Study Overview
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Brief Summary
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The purpose of this study is to establish the dose regimen and evaluate the preliminary efficacy and the safety/tolerability of poziotinib in participants with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer who have received at least two prior HER2-directed treatment regimens.

Detailed Description
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This is a phase 2, open-label, multicenter study to establish the dose regimen and evaluate the preliminary efficacy and the safety/tolerability of poziotinib in participants with HER2-positive metastatic breast cancer who have received at least two prior HER2-directed treatment regimens. Each treatment cycle will be 21 days in duration. During each 21-day cycle, participants who are eligible for participation will receive poziotinib orally once daily. All treated participants will be followed up until disease progression, death, intolerable adverse events or up to a maximum of 24 months whichever comes earlier.

Official Title
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A Phase 2 Study of Poziotinib in Patients With HER2-Positive Metastatic Breast Cancer (MBC) Who Have Received Prior HER2 Regimens for MBC

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: Poziotinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histopathologically confirmed primary breast cancer with metastatic lesions. Confirmed HER2 overexpression or gene-amplified tumor At least two prior HER2-directed therapy regimens for breast cancer, including trastuzumab and trastuzumab emtansine Measurable disease per Response Evaluation Criteria for Solid Tumors version 1.1 (RECIST v1.1) Participant is at least 18, and ≤90 years of age. Adequate hematologic, hepatic, and renal function Eastern Cooperative Oncology Group (ECOG) performance status <= 2 Exclusion Criteria: Previous treatment with poziotinib prior to study participation Brain metastases that are symptomatic or require therapy to control symptoms, as well as any history of radiation, surgery, or other therapy, including steroids, to control symptoms from brain metastases within 15 days of enrollment. Anticancer chemotherapy, biologics, immunotherapy, cure-intent radiotherapy, or investigational treatment within 15 days, except for hormone therapy, palliative therapy, or supportive therapy. History of congestive heart failure Class III/IV according to the New York Heart Association (NYHA) Functional Classification or serious cardiac arrhythmias requiring treatment. Cardiac ejection fraction <50% History of other malignancies within the last 5 years Participant is pregnant or breast-feeding. Unable to take drugs orally

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1: Poziotinib 24 mg<br>Participants received poziotinib 24 milligrams (mg), administered as three 8 mg tablets, orally, once daily (QD) on an intermittent dosing schedule of 14 days on treatment followed by 7 days off treatment, in a 21-day cycle until disease progression, death, intolerable adverse events (AEs) or for up to a maximum of 24 months, whichever occurs first. | Drug: Poziotinib<br>* 8 mg oral tablets, administered QD.<br>* Other names: HM781-36B;|
| Experimental: Cohort 2: Poziotinib 16 mg<br>Participants received poziotinib 16 mg, administered as two 8 mg tablets, orally, QD, on a continuous dosing schedule in a 21-day cycle until disease progression, death, intolerable AEs or for up to a maximum of 24 months, whichever occurs first. | Drug: Poziotinib<br>* 8 mg oral tablets, administered QD.<br>* Other names: HM781-36B;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) | ORR was defined as the percentage of participants whose best overall response (BOR) was complete response (CR) or partial response (PR) among participants in the Evaluable Population assessed per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). ORR was based on investigator assessed BOR. Per RECIST v1.1 for target lesions, CR was disappearance of all target tumor lesions (TLs) and all target lymph nodes (LNs) with short axis <10mm. PR was ≥30% decrease in sum of diameters (SOD) from Baseline, and not progressive disease (PD) (≥20% increase in SOD from previous smallest SOD on study, and an absolute increase of ≥5mm). | Up to 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) | PFS was the duration of time (in months) from first administration of study treatment to date of first documented disease progression or death from any cause. PFS of living participants without documented PD was censored at the time of last tumor assessment or the date of first treatment if there was no post-baseline tumor assessment. Per RECIST v1.1 for target lesions, PD was defined as ≥20% increase in SOD from previous smallest SOD on study, and an absolute increase of ≥5mm. | Up to 24 Months | 
| Disease Control Rate (DCR) | DCR was the percentage of participants whose best response was CR, PR or stable disease (SD) among participants in the Evaluable Population assessed per RECIST v1.1. DCR was based on investigator-assessed BOR. Per RECIST v1.1 for target lesions, CR was defined as disappearance of all target TLs and all target LNs with short axis <10mm. PR was ≥30% decrease in sum of diameters (SOD) from Baseline, and not progressive disease (≥20% increase in SOD from previous smallest SOD on study, and an absolute increase of ≥5mm). SD was SOD change neither sufficient for PR nor sufficient for PD. | Up to 24 months | 
| Time to Progression (TTP) | TTP was defined as the time (in months) from first administration of study drug to tumor progression, which excluded death without tumor progression, by the end of study. TTP of participants who died without documented PD was censored at date of death. TTP of living participants without documented PD was censored at the same time as PFS, which was the last tumor assessment or the date of first treatment if there was no post-baseline tumor assessment. Per RECIST v1.1 for target lesions, PD was defined as ≥20% increase in SOD from previous smallest SOD on study, and an absolute increase of ≥5mm. | Up to 24 months | 
| Duration of Response (DoR) | DoR was evaluated only for participants whose BOR was CR or PR and was defined as the time (in months) from the date that response evaluation criteria were first met for CR or PR (whichever status was recorded first) until the first subsequent date that PD or death was documented. DoR of participants without documented PD or death was censored at the time of last tumor assessment. Per RECIST v1.1 for target lesions, CR was defined as disappearance of all target tumor lesions (TLs) and all target lymph nodes (LNs) with short axis <10mm. PR was defined as ≥30% decrease in sum of diameters (SOD) from Baseline, and not PD. PD was defined as ≥20% increase in SOD from previous smallest SOD on study, and an absolute increase of ≥5mm). | Up to 24 months | 
| Number of Participants With One or More Treatment-Emergent Adverse Events (TEAEs) | An AE was defined as any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. TEAEs were AEs that occurred or worsened from the first dose of study treatment until 35 (± 5) days after the last dose of study treatment. | From the first dose of study drug administration until 35 (± 5) days after the last dose of study drug administration (Up to approximately 25 months) | 
| Pharmacokinetic Analysis (Drug Concentration Measurements) |  | For Cohort 1: Pre-dose and 1 and 2 hours post-dose on Day 1 of Cycles 1, 2, and 3, and pre-dose on Day 14 of Cycle 1 For Cohort 2: Day 1 of Cycle 1 pre-dose and 30 minutes, 1,1.5,2,3, 4, 6, and 24 hours post-dose of Day 1 of Cycle 1 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Poziotinib, Metastatic Breast Cancer, HER2-positive, Pan-HER inhibitor