Poziotinib in Patients With HER2+ Recurrent Stage IV BC Who Have Received at Least 2 Prior HER2-directed Regimens

A Prospective, Open-label, Single-arm, Multi-Center, Phase II Trial of NOV120101 in Patients With HER2-overexpressed Recurrent Stage IV Breast Cancer Who Have Received at Least 2 Prior HER2-directed Regimens

The purpose of this study is to evaluate the efficacy and safety of novel pan-HER inhibitor, NOV120101 (Poziotinib), in HER2-overexpressed recurrent stage IV breast cancer patients who received at least 2 prior HER2-directed regimens.

Study Overview

• Status: Completed
• Conditions: Metastatic Breast Cancer
• Intervention / Treatment: Drug: NOV120101 (Poziotinib)

Detailed Description

To evaluate the efficacy of NOV120101 (Poziotinib) as a therapeutic agent for HER2-overexpressed recurrent stage IV breast cancer, patients who have received at least two prior HER2-directed regimens will be enrolled in this study. Subjects will receive NOV120101 (Poziotinib) 12 mg PO once daily for 2 weeks followed by 1-week drug-free intervals between cycles until disease progression or unacceptable toxicity development. Progression Free Survival (PFS) will be analyzed as the primary endpoint in this trial. Secondary endpoints including PFS rate at 12 weeks, ORR, DCR, OS and TTP will also be analyzed.

• Study Type: Interventional
• Enrollment (Actual): 106
• Phase: Phase 2

Contacts and Locations

Study Locations

• Korea, Republic of
  • Chungcheongbuk-do
    • Cheongju-si, Chungcheongbuk-do, Korea, Republic of, 361-711
      • Chungbuk National University Hospital
  • Gyeonggi-do
    • Goyang-si, Gyeonggi-do, Korea, Republic of, 410-769
      • National Cancer Center
    • Seongnam-si, Gyeonggi-do, Korea, Republic of, 463-707
      • Seoul National University Bundang Hospital
  • Seoul
    • Gangnam-gu, Seoul, Korea, Republic of, 135-710
      • Samsung Medical Center
    • Jongno-gu, Seoul, Korea, Republic of, 110-744
      • Seoul National University Hospital
    • Seodaemun-gu, Seoul, Korea, Republic of, 120-752
      • Severance Hospital
    • Songpa-gu, Seoul, Korea, Republic of, 138-736
      • Asan Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Who give agreement to the collection of tumor tissue specimen suitable for biomarker research
2. ECOG performance status ≤ 2

3. Who received following treatments as Taxane-based chemotherapy and at least two HER2-targeted* therapy including Trastuzumab.

   * lapatinib, T-DM1 (trastuzumab emtansine), pertuzumab

4. Adequate hematological, hepatic and renal functions

Exclusion Criteria:

1. Who received NOV120101 prior to participation in this study
2. Patients expected to exhibit hypersensitivity to IP or its components
3. Any other concurrent chemotherapies
4. Concurrent or prior radiotherapy within 4 weeks before study participation. However, patients with additional lesions other than the major lesion who completed and recovered from all treatment-related toxicities after radiotherapy in a limited area as a palliative therapy are allowed to participate in the study
5. History of symptomatic or unstable angina and congestive heart failure; arrhythmia requiring medications; or clinically significant myocardial infarction or other cardiac diseases within 6 months before study participation for which any related-significant risks are expected
6. Patients whose left ventricle ejection fraction (LVEF) is below the institutional lower limit of normal. However, if no lower limit of normal is defined in the site, the lower limit or normal is 50%.
7. Concurrent active hepatic or biliary disease (with exception of Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver diseases)
8. History or concurrent ongoing/active infection, or uncontrolled diseases including, but not limited to, psychiatric illness/social situations which may limit the compliance with study procedures
9. Prior chemo-, immuno-, or surgical therapy within 3 weeks, or hormone therapy within 1 week before IP administration
10. History of primary malignancies other than breast cancer.
11. Patients with central nervous system (CNS) metastases.
12. Patients receiving or expected to receive bisphosphonate for prophylactic use without any bone-related diseases during the trial, for the exception of the treatment for bone metastases or osteoporosis initiated prior the IP administration.
13. Clinically significant or recent acute gastrointestinal disorders with diarrhea as a major symptom
14. Who are unstable or with unresolved severe adverse event(s)
15. Pregnancy or breast-feeding
16. Women of childbearing potential or men who are unwilling to use adequate contraception or be abstinent during the trial and for at least 2 months after the end of treatment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NOV120101 (Poziotinib); Single arm study with NOV120101(poziotinib) 12 mg PO once daily for 2 weeks followed by a 1-week drug-free interval	Drug: NOV120101 (Poziotinib); NOV120101 (Poziotinib) 12 mg PO once daily for 2 weeks followed by a 1-week drug-free interval between cycles until disease progression or unacceptable toxicity development; Other Names: Poziotinib; HM781-36B

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Progression free survival (PFS)	By 12 months after enrollment of the last subject

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PFS rate at Week 12		12 weeks
Objective Response Rate (ORR)	the proportion of patients with complete response (CR) and/or partial response (PR)	By 12 months after enrollment of the last subject
Disease Control Rate (DCR)	the proportion of patients with CR, PR and/or stable disease (SD)] [Safety Issue?	By 12 months after enrollment of the last subject
Duration of Disease Control		By 12 months after enrollment of the last subject
Overall Survival (OS)		By 12 months after enrollment of the last subject
Time To Progression (TTP)		By 12 months after enrollment of the last subject
Time to objective response		By 12 months after enrollment of the last subject
Duration of objective response		By 12 months after enrollment of the last subject

Other Outcome Measures

Outcome Measure	Time Frame
Number of Participants with Adverse Events as a Measure of Safety and Tolerability	2 years
Population pharmacokinetics (PK) of NOV120101 (Poziotinib) - Ka, CL(clearance), Vd(volume of distribution)	4 weeks

Collaborators and Investigators

• Sponsor: Hanmi Pharmaceutical Company Limited

Publications and helpful links

General Publications

• Kim JY, Park K, Im SA, Jung KH, Sohn J, Lee KS, Kim JH, Yang Y, Park YH. Clinical implications of HER2 mRNA expression and intrinsic subtype in refractory HER2-positive metastatic breast cancer treated with pan-HER inhibitor, poziotinib. Breast Cancer Res Treat. 2020 Dec;184(3):743-753. doi: 10.1007/s10549-020-05891-0. Epub 2020 Aug 28.

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2015
• Primary Completion (Actual): June 1, 2017
• Study Completion (Actual): April 1, 2021

Study Registration Dates

• First Submitted: January 19, 2015
• First Submitted That Met QC Criteria: April 13, 2015
• First Posted (Estimate): April 16, 2015

Study Record Updates

• Last Update Posted (Actual): January 20, 2022
• Last Update Submitted That Met QC Criteria: January 5, 2022
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: NOV120101-203

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No