A Study to Evaluate the Efficacy and Safety of Margetuximab Plus Chemotherapy in the Treatment of Chinese Patients With HER2+ MBC

NCT04262804 | Unknown Phase 2

• 1 other identifier: ZL-1302-002
• Study Type: interventional
• Target: 123
• Locations: 1 country
• Sites: 1

Brief Summary

This is a randomized, open-label, multi-center, Phase II clinical study to evaluate the efficacy and safety of margetuximab plus chemotherapy compared with trastuzumab plus chemotherapy in Chinese patients (Mainland, Hong Kong and Taiwan) with advanced HER2+ breast cancer who have received at least 2 prior lines of anti-HER2 directed therapy in the metastatic setting (mandatory including trastuzumab). The primary endpoint of this study is PFS evaluated by BICR. The secondary endpoints are OS, PFS evaluated by investigator, ORR, DoR, CBR, safety and tolerability, the impact of ADA, and the popPK profile

Conditions

Breast Cancer Metastatic

Keywords

Breast Cancer Metastatic; MBC; Margetuximab

Outcome Measures

Primary Outcomes (1)

• PFS assessed by BICR (RECIST 1.1)

  the time from randomization date to the date of first documented disease progression or death from any cause, whichever occurs first. The confirmation of disease progression is per RECIST 1.1, and evaluation made by BICR

  Approximately 18 months after the first subject is randomized; anticipated evaluation Jul 2020.

Secondary Outcomes (6)

• Overal Survival (OS)

  Approximately 15 months after the last subject is randomized

• PFS assessed by Investigator

  Approximately 18 months

• Objective Response Rate (ORR) assessed by BICR

  Approximately 18 months

• Duration of Response (DoR) assessed by BICR

  the time from initial response to date of first documented disease progression or death from any cause, whichever occurs first

• Clinical Beneficial Rate (CBR)

  Approximately 18 months

Study Arms (2)

Margetuximab & Chosen Chemotherapy

EXPERIMENTAL

The dosage and administering of margetuximab is 15 mg/kg IV every 21 days. Investigators need to chose one of the 3 chemotherpies based on patient conditions.

Drug: Margetuximab; Drug: Chosen Chemotherapy (Capecitabine); Drug: Chosen Chemotherapy (Vinorelbine ); Drug: Chosen Chemotherapy (Gemcitabine )

Trastuzumab & Chosen Chemotherapy

ACTIVE COMPARATOR

The dosage and administering of Trastuzumab is 8 mg/kg loading dose then 6 mg/kg IV every 21 days. Investigators need to chose one of the 3 chemotherpies based on patient conditions.

Drug: Trastuzumab; Drug: Chosen Chemotherapy (Capecitabine); Drug: Chosen Chemotherapy (Vinorelbine ); Drug: Chosen Chemotherapy (Gemcitabine )

Interventions

Margetuximab DRUG

Margetuximab IV

Margetuximab & Chosen Chemotherapy

Trastuzumab DRUG

Trastuzumab IV

Trastuzumab & Chosen Chemotherapy

Chosen Chemotherapy (Capecitabine) DRUG

Capecitabine tablet

Margetuximab & Chosen Chemotherapy; Trastuzumab & Chosen Chemotherapy

Chosen Chemotherapy (Vinorelbine ) DRUG

Vinorelbine IV

Margetuximab & Chosen Chemotherapy; Trastuzumab & Chosen Chemotherapy

Chosen Chemotherapy (Gemcitabine ) DRUG

Gemcitabine IV

Margetuximab & Chosen Chemotherapy; Trastuzumab & Chosen Chemotherapy

Eligibility Criteria

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

You may qualify if:

• 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. Note: the definition of HER2 positive is to have at least once 3+ by IHC, FISH positive and CISH positive in the pathological test/retesting conducted at least once by investigational site or qualified central lab which met national standard.
• Have received at least 2 prior lines of anti-HER2 directed therapy in the metastatic setting (mandatory to have trastuzumab, and other anti-HER2 agents e.g. lapatinib, pyrotinib, pertuzumab, or T-DM1), regardless of having received (neo)adjuvant anti-HER2 therapy or not
• Have received treatment with no more than three 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.
• Prior radiotherapy, chemotherapy, hormonal therapies are allowed
• Endocrine therapies will not be considered as previous lines of therapy in the metastatic setting.
• Prior neo-adjuvant or adjuvant therapy that resulted in relapse within 6 months of the completion of therapy will be considered a line of treatment for metastatic disease.
• Dose interruptions, delays, pauses during previous therapy, or changes in therapy to manage toxicity will not constitute a new line of therapy provided disease progression did not occur
• Subject has at least one measurable lesion 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 randomization and has adequate organ functions as defined below:
• Absolute Neutrophil count (≥ 1.5 \*109/L)

You may not qualify if:

• Subject has symptomatic, uncontrolled brain or pia mater metastasis. If subject has known and treated brain metastasis, baseline CT or MRI data within 4 weeks prior to randomization are mandatory to be obtained. Subject should have received brain metastasis treatment for at least four weeks before randomization. If subject needs to use steroids for treatment after randomization, the dosage of steroids (\<10 mg/day prednisone or equivalent) should be stable before randomization for at least four weeks without relevant neurological symptoms
• Subject has third interstitial effusion (e.g. massive pleural and ascites) that cannot be controlled by drainage or other means.
• Subject has local or systemic anti-tumor treatment within 2 weeks prior to randomization, including radiotherapy, chemotherapy, surgical resection (major surgery for breast cancer), or target therapy, and endocrine therapy for anti-tumor within 7 days prior to randomization.
• Subject has any investigational treatment within 4 weeks prior to randomization (including margetuximab)
• Subject has history of major surgery with unrecovered surgical effect within 4 weeks prior to randomization.
• 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 randomization.
• Subject has severe and uncontrolled disease, including but not limited to
• Uncontrollable nausea and vomiting, and any other severe gastrointestinal disorders
• Active viral infections, e.g. human immunodeficiency virus (HIV), hepatitis B (HBV; HbsAg positive, HBV-DNA (≥103 copies/ml or (≥500 IU/ml), hepatitis C (HCV) etc.
• Severe uncontrollable diabetes, hypertension, thyroid diseases etc.
• Severe uncontrollable pulmonary diseases, e.g. severe contagious pneumonia, interstitial lung disease etc.
• Myocardial infarction, unstable angina pectoris, stroke, transient ischemic attack within 6 months prior to randomization; clinically significant arrhythmia, congestive heart failure (NYHA II-IV), pericarditis or severe pericardial effusion, myocarditis, etc.
• Subject has known allergy to recombinant proteins, polysorbide 80, benzyl alcohol or any excipients contained in manufacturing of margetuximab, trastuzumab or other study treatments. For subject with previous transfusion reactions to trastuzumab or other monoclonal antibodies, if there is no contraindication for trastuzumab treatment, the subject is eligible for enrollment.
• Subject has contraindication of using trastuzumab, or confounding disease that may prevent subject from using chemotherapy prescribe by the investigator.
• Subject has vaccination with any live virus vaccine within four weeks prior to randomization; inactivated influenza vaccine is allowed.

Sponsors & Collaborators

• Zai Lab (Shanghai) Co., Ltd.: lead

Study Sites (1)

National Taiwan University Hospital

Taipei, Taiwan

Location

Related Publications (1)

• Zhang Q, Ouyang Q, Li W, Chiu J, Yan M, Lu YS, Sun S, Li H, Du Y, Wang X, Sun T, Yin Y, Wang H, Ye F, Shen K, Wang J, Pan Y, Wang S, Yang J, Wu X, Dai MS, Cheng J, Teng Y, Su F, Wu X, He J, Fu P, Yang L, Xin Y, Wang X, Jiang Z. Efficacy and safety of margetuximab plus chemotherapy vs. trastuzumab plus chemotherapy in Chinese patients with pretreated HER2-positive advanced metastatic breast cancer: results from a randomized, open-label, multicenter, phase II bridging study. Transl Breast Cancer Res. 2022 Oct 31;3:31. doi: 10.21037/tbcr-22-35. eCollection 2022.

  PMID: 38751523 DERIVED

MeSH Terms

Interventions

margetuximab; Trastuzumab; Capecitabine; Vinorelbine; Gemcitabine

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines

Study Design

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

Study Record Dates

• First Submitted: January 30, 2020
• First Posted: February 10, 2020
• Study Start: January 13, 2020
• Primary Completion: September 3, 2021
• Study Completion: December 1, 2023
• Last Updated: August 22, 2023

Record last verified: 2023-08

Locations

TW (1)