A Study to Evaluate the Pharmacokinetics of Margetuximab in Chinese Patients With HER2+ MBC

An Open-Label, Single-arm, Phase I Study to Evaluate the Pharmacokinetics, Tolerability and Safety of Margetuximab Plus Chemotherapy in the Treatment of Chinese Patients With HER2+ Metastatic Breast Cancer Who Have Received Prior Anti-HER2 Therapies

This is an open-label, Single-arm, Phase I clinical study to evaluate the pharmacokinetics, tolerability and safety of margetuximab plus chemotherapy in Chinese patients with advanced HER2+ breast cancer who have received standard anti-HER2 directed therapy in the metastatic setting (mandatory including trastuzumab).

The primary endpoint of this study is PK parameters of margetuximab.

Study Overview

• Status: Completed
• Conditions: HER2 Positive Metastatic Breast Cancer
• Intervention / Treatment: Drug: Margetuximab Margetuximab-IV

Detailed Description

Approximately 16~20 Chinese subjects will be enrolled. Eligible subjects are HER2 positive, metastatic breast cancer who has received standard anti-HER2 directed therapy in the metastatic setting in Chinese patients. Subjects should have received treatment with at least one, and no more than four lines of therapy overall in the metastatic setting.

Eligible subjects will receive margetuximab plus chemotherapy. The dosage and administering of margetuximab is 15 mg/kg IV Q3W. Investigators selected one of three backbone chemotherapy regimens given at standard doses: capecitabine, vinorelbine or gemcitabine. Subject will receive the treatment until disease progression, unacceptable toxicity, withdrawal of consent, initiation of subsequent anti-tumor treatment therapy, or death (whichever occurs first).

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100071
      • The fifth medical center of the General Hospital of people's Liberation Army of China
  • Hebei
    • Shijiazhuang, Hebei, China, 050000
      • The Fourth Hospital of Hebei Medical University
  • Henan
    • Zhengzhou, Henan, China, 450000
      • Henan Cancer Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Written informed consent obtained prior to performing any protocol-related procedures
• Male or female, age ≥ 18 years old at the time of screening.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Subject has histologically confirmed HER2 positive metastatic breast cancer.
• Have received standard anti-HER2 directed therapy in the metastatic setting (mandatory to have trastuzumab), regardless of having received (neo)adjuvant anti-HER2 therapy or not.
• Have received treatment with no more than four lines of therapy overall in the metastatic setting (including anti-HER2 targeted therapy or chemotherapy) and must have disease progressed on or after, the most recent line of therapy. per RECIST 1.1.
• Previous adverse events associated with anti-tumor therapy have been recovered to NCI-CTCAE v4.03 Grade ≤1 (except NCI-CTCAE v4.03 Grade ≤2 alopecia, stable sensory neuropathy, or stabilized electrolyte disturbance after fluid transfusion).
• Subject has life expectancy ≥12 weeks.
• Subject has no supportive therapy of blood transfusion or growth factor within 4 weeks before dosed and has adequate organ functions
• Subject has a negative test result of pregnancy test at screening.

Exclusion Criteria:

• Subject has symptomatic, uncontrolled brain or pia mater metastasis.
• Subject has third interstitial effusion that cannot be controlled by drainage or other means.
• Subject has local or systemic anti-tumor treatment within 2 weeks prior to enrollment
• Subject has any investigational treatment within 4 weeks prior to enrollment (including margetuximab)
• Subject has history of major surgery with unrecovered surgical effect within 4 weeks prior to enrollment
• Subject has other malignant tumor (complete cured in situ cervical cancer, cutaneous basal cell carcinoma or cutaneous squamous cell carcinoma are not included) within 5 years prior to enrollment
• Subject has severe and uncontrolled disease

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: Margetuximab & Chosen Chemotherapy; The dosage and administering of margetuximab is 15 mg/kg IV every 21 days. Investigators need to choose one of the 3 chemotherapies based on patient conditions.	Drug: Margetuximab Margetuximab-IV; Drug: Chosen Chemotherapy (Capecitabine) -Oral Capecitabine tablet Drug: Chosen Chemotherapy (Vinorelbine) Vinorelbine -IV Drug: Chosen Chemotherapy (Gemcitabine) Gemcitabine -IV

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Evaluation of pharmacokinetic parameter of margetuximab Cmax	Approximately 18 months after the first subject is randomized; anticipated evaluation Jul 2020
Evaluation of pharmacokinetic parameter of margetuximab Tmax	Approximately 18 months after the first subject is randomized; anticipated evaluation Jul 2020
Evaluation of pharmacokinetic parameter of margetuximab T1/2	Approximately 18 months after the first subject is randomized; anticipated evaluation Jul 2020
Evaluation of pharmacokinetic parameter of margetuximab AUC	Approximately 18 months after the first subject is randomized; anticipated evaluation Jul 2020

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Treatment-Emergent Adverse Events	Incidence of Treatment-Emergent Adverse Events as assessed by CTC AE 4.03	Approximately 18 months after the first subject is randomized; anticipated evaluation Jul 2020

Collaborators and Investigators

• Sponsor: Zai Lab (Shanghai) Co., Ltd.
• Investigators: Principal Investigator: Zeifei Jiang, The fifth medical center of the General Hospital of people's Liberation Army of China; Principal Investigator: Cuizhi Geng, The Fourth Hospital of Hebei Medical University

Study record dates

Study Major Dates

• Study Start (Actual): August 25, 2020
• Primary Completion (Actual): April 27, 2021
• Study Completion (Actual): April 27, 2021

Study Registration Dates

• First Submitted: May 8, 2020
• First Submitted That Met QC Criteria: May 20, 2020
• First Posted (Actual): May 21, 2020

Study Record Updates

• Last Update Posted (Actual): June 14, 2021
• Last Update Submitted That Met QC Criteria: June 11, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: HER2; Metastatic Breast Cancer; MBC; Margetuximab
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Antineoplastic Agents; Margetuximab
• Other Study ID Numbers: ZL-MG-BC-001

Drug and device information, study documents

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