Safety and efficacy Assessment of Trastuzumab emtansine of Cadila Healthcare Ltd in comparison with Reference drug(Trastuzumab emtansine) for the treatment of metastatic breast cancer

INTERVENTION: Intervention1: Trastuzumab emtansine (ZRC‐3256, Cadila Healthcare Ltd): Dosage: 3.6 mg/kg given as an intravenous infusion every 3 weeks (21 days cycle) Duration of Treatment: 8 Cycles Control Intervention1: Trastuzumab emtansine (Reference product, Kadcyla®: Roche Products): Dosage: 3.6 mg/kg given as an intravenous infusion every 3 weeks (21 days cycle) Duration of Treatment: 8 Cycles CONDITION: HER2‐ positive, metastatic breast cancer PRIMARY OUTCOME: To compare the overall response rate (ORR) following administration of ZRC‐3256 (Cadila Healthcare Limited) and Kadcyla® in patients with metastatic breast cancer based on Response Evaluation Criteria in Solid Tumors (RECIST, Version 1.1) achieved at end of 24 weeks.‐‐‐‐‐‐Timepoint: Timeframe: Week 0 (baseline), week 24 (visit 15) SECONDARY OUTCOME: 1. To compare the pharmacokinetic parameters (Cmax, AUC0‐t ) ; 2. To compare the incidence and titres of Anti‐Drug Antibodies at the end of 12 weeks (visit 11) and 24 weeks treatment (visit 15) ; 3. Comparative safety for treatment emergent adverse events by monitoring of significant clinical signs and symptoms and laboratory abnormalities‐‐‐‐‐‐Timepoint: 1)Cycle 1 ; 2)Week 0 (baseline), week 12 and week 24 (visit 15) ; 3)Throughout the study. INCLUSION CRITERIA: 1.Female subjects of age 18 to 65 years (both inclusive). 2.Subject with pathologically (histologically or cytologically) confirmed, uni‐dimensionally measurable invasive metastatic breast cancer. 3.Subjects with a strong HER‐2 over‐expression as described by a 3+ score by immunohistochemistry (IHC) or a positive fluorescence in‐situ hybridization (FISH). 4.For the treatment of subjects with HER2‐positive, metastatic breast cancer who previously received trastuzumab and a taxane, separately or in combination. Subject should have either: â?¢ Received prior therapy for metastatic disease, or â?¢ Developed disease recurrence during or within six months of completing adjuvant therapy. 5.Subject with Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1. 6.Left ventricular ejection fraction (LVEF) â?¥50% by 2 D ECHO. 7.Subjects with following laboratory results: <