A Randomized, Open-Label, Multiple-center, Phase II Study to Evaluate the Efficacy and Safety of Margetuximab Plus Chemotherapy vs Trastuzumab Plus Chemotherapy in the Treatment of Chinese Patients With HER2+ Metastatic Breast Cancer Who Have Received Prior Anti-HER2 Therapies
Overview
- Phase
- Phase 2
- Intervention
- Margetuximab
- Conditions
- Breast Cancer Metastatic
- Sponsor
- Zai Lab (Shanghai) Co., Ltd.
- Enrollment
- 123
- Locations
- 1
- Primary Endpoint
- PFS assessed by BICR (RECIST 1.1)
- Status
- Active, not recruiting
- Last Updated
- 2 years ago
Overview
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
Detailed Description
Approximately 120 Chinese subjects will be enrolled and randomized to treatment group and control group in 1:1 fashion, approximately 60 subjects in each group. Eligible subjects are HER2 positive, metastatic breast cancer who has 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, and pertuzumab; in case of having received (neo)adjuvant anti-HER2 therapy) in Chinese patients (Mainland, Hong Kong and Taiwan). Subjects should Have received treatment with at least one, and no more than three, lines of therapy overall in the metastatic setting (including anti-HER2 directed therapy and chemotherapy, and patients must have progressed on or following, the most recent line of therapy, based on RECIST 1.1. Eligible subjects will be randomized 1:1 to receive margetuximab plus chemotherapy compared with trastuzumab plus chemotherapy. The dosage and administering of margetuximab is 15 mg/kg IV Q3W. Trastuzumab was administered 8 mg/kg loading dose, 6 mg/kg subsequent doses, IV Q3W. Prior to randomization to either margetuximab or trastuzumab, investigators selected one of four backbone chemotherapy regimens given at standard doses: capecitabine, vinorelbine or gemcitabine. Capecitabine and vinorelbine should be selected in priority. Gemcitabine could be selected only if capecitabine and vinorelbine were used in previous treatment. 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). Subject is not allowed to crossover after disease progression. Randomization was stratified by number of metastatic sites (≤2, \>2) and chemotherapy chosen. The definition of HER2 positive is to have at least once 3+ by IHC, FISH positive or CISH positive in the pathological test/retesting. Subject should provide original biopsy/surgical excision tissue sample/latest follow-up sample after randomization, for the centralized test and review when necessary.
Investigators
Eligibility Criteria
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. 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.
- •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
Exclusion Criteria
- •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.
Arms & Interventions
Margetuximab & Chosen Chemotherapy
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.
Intervention: Margetuximab
Margetuximab & Chosen Chemotherapy
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.
Intervention: Chosen Chemotherapy (Capecitabine)
Margetuximab & Chosen Chemotherapy
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.
Intervention: Chosen Chemotherapy (Vinorelbine )
Margetuximab & Chosen Chemotherapy
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.
Intervention: Chosen Chemotherapy (Gemcitabine )
Trastuzumab & Chosen Chemotherapy
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.
Intervention: Trastuzumab
Trastuzumab & Chosen Chemotherapy
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.
Intervention: Chosen Chemotherapy (Capecitabine)
Trastuzumab & Chosen Chemotherapy
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.
Intervention: Chosen Chemotherapy (Vinorelbine )
Trastuzumab & Chosen Chemotherapy
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.
Intervention: Chosen Chemotherapy (Gemcitabine )
Outcomes
Primary Outcomes
PFS assessed by BICR (RECIST 1.1)
Time Frame: Approximately 18 months after the first subject is randomized; anticipated evaluation Jul 2020.
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
Secondary Outcomes
- Objective Response Rate (ORR) assessed by BICR(Approximately 18 months)
- FcγR(at baseline (before first dose of treatment))
- PFS assessed by Investigator(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)
- Overal Survival (OS)(Approximately 15 months after the last subject is randomized)
- Clinical Beneficial Rate (CBR)(Approximately 18 months)