This is a Phase 3 Study to Evaluate the Efficacy, Safety, Immunogenicity and Pharmacokinetics of Proposed Trastuzumab Emtansine Biosimilar Compared with Kadcyla in HER2-positive Breast Cancer Patients
- Conditions
- Health Condition 1: C00-D49- Neoplasms
- Registration Number
- CTRI/2024/08/072580
- Lead Sponsor
- Intas Pharmaceuticals Limited
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Yet Recruiting
- Sex
- Not specified
- Target Recruitment
- 0
1) Participant must sign an ICF indicating that the participant understands the purpose of, and procedures required for the study as described in Appendix10.1.3 and in this protocol and is willing to participate in the study. 2) Female (according to their chromosomal composition at birth). 3) Age of greater than or equal to 18 years (completed years) at the time of signing the informed consent.
4) Participants who have documented histologically or cytologically confirmed invasive breast cancer with either of the following:•Incurable, unresectable, locally advanced (as per AJCC 8th edition) breast cancer previously treated with multimodality therapy and are currently not amenable to resection with curative intent.• Metastatic breast cancer (as per AJCC 8th edition) 5) Participant has documented history of HER2 positive (as per most recent version of American Society of Clinical Oncology [ASCO] and the College of American Pathologists [CAP] Guidelines [2]) breast cancer on the most recently available tumor tissue sample available (primary tumor and/or metastatic site). If not available, HER2 status must be documented from a local laboratory that is experienced/certified in HER2-expression testing using an accurate and validated assay. For participants with bilateral breast cancer, HER2 positivity must be demonstrated either in both locations or in a metastatic biopsy.
6) Prior treatment for breast cancer in either neoadjuvant, adjuvant, unresectable, locally advanced, or metastatic setting must include both:•A taxane, alone or in combination with another agent, AND •Trastuzumab, alone or in combination with another agent •Prior radiotherapy, hormonal therapies, and other anti-HER2 therapies are allowed 7) Documented progression of incurable unresectable, locally advanced, or metastatic breast cancer after the most recent line of therapy, defined by the investigator:•Progression must occur during or after most recent treatment for locally advanced/MBC OR •Progression must occur within 6 months after completing neoadjuvant or adjuvant systemic chemotherapy 8
Recovery to baseline or less than or equal to Grade 1 per Common Terminology Criteria for Adverse Events (CTCAE) v5 from toxicities related to any prior treatments, unless AE(s) are clinically nonsignificant and/or stable on supportive therapy as determined by the Investigator before randomization. 9) Has at least one measurable lesion as defined by RECIST v1.1 (Refer Appendix 5) at baseline:•Any potentially measurable lesion that has been previously treated with radiotherapy should be considered as a non-measurable lesion. However, it can be considered as a measurable lesion if a lesion previously treated with radiotherapy has clearly progressed unequivocally ? based on imaging since last dose of the radiotherapy AND the previously irradiated lesion is not the only site of disease.•Lesions that are intended to be used or were to collect tissue samples for biopsy should not be counted as target lesions.•If only one measurable lesion exists, it is acceptable to be used (as a target lesion) as long as it has not been previously irradiated and baseline tumor assessment scans are done at least 14 days after the biopsy is performed.•Brain lesions will be considered as non-target lesions only 10) Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at screening and before randomization.
11) Contraceptive use by participants should be consistent w
1) Documented medical history of uncontrolled, clinically significant intercurrent cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, rheumatologic, psychiatric, or metabolic disturbances or any other medical condition(s) for which, in the opinion of the investigator, participation would not be in the best interest of the participant (eg, compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments.2) Known allergies, hypersensitivity, or intolerance to any of the study interventions, or components (including murine proteins) / excipients thereof (refer to the Kadcyla® product information [3]), or drug or other allergy that, in the opinion of the investigator, contraindicates participation in the study.3) History of intolerance (such as Grade 3 to 4 infusion reaction) or permanent discontinuation due to infusion-related reactions (IRR) to trastuzumab. 4) Significant allergies to humanized monoclonal antibodies. 5) Prior treatment with trastuzumab emtansine or trastuzumab deruxtecan or any other anti-HER2 ADCs in any setting 6) Peripheral neuropathy of Grade greater than or equal to 2 per NCI CTCAE version 5.0 at screening visit as assessed by investigator.7) Had major surgical procedure within 4 weeks before screening, or will not have fully recovered from surgical procedure, or has surgical procedure planned during the time the participant is expected to participate in the study.NOTE: Participants with planned surgical procedures to be conducted under local anesthesia may participate.8) Presence of hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) at screening or within 3 months prior to first dose of investigational intervention.9) Positive hepatitis C antibody test result at screening or within 3 months prior to starting investigational intervention. NOTE: Participants with positive hepatitis C antibody due to prior resolved disease can be enrolled only if a confirmatory negative hepatitis C RNA test is obtained 10Has known human immunodeficiency virus (HIV) seropositive status, or positive HIV antibody test at screening.
11) Participants with a prior or concurrent malignancy (except disease under study) whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the study intervention.
12) Systemic treatment with anticancer therapy including biologic, immunotherapy, retinoid therapy within 3 weeks before randomization; hormonal anti-cancer therapy within 1 weeks before randomization. Recovery of treatment-related toxicity must be consistent with other eligibility criteria.
13) Radiation therapy within 2 weeks before randomization; recovery of treatment-related toxicity consistent with other eligibility criteria. Palliative radiation therapy is allowed as mentioned in section 6.9.
14) Current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice, or cirrhosis. NOTE: Stable chronic liver disease (including Gilbert’s syndrome, asymptomatic gallstones is acceptable if the participant otherwise meets entry criteria.
15) Participant with clinically significant current or recent (within the past 6 months before randomization [unless otherwise specified below]) cardiac conditions: a. Uncontrolled hypertension (defined as s
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Overall response rate (ORR) based on blinded independent central review. ORR is defined as the proportion of participants with the best overall response of complete response (CR) or partial response (PR) according to RECIST version 1.1 criteria. A response confirmation is not requiredTimepoint: Upto approximately 24 weeks
- Secondary Outcome Measures
Name Time Method Cmax, AUC0-t, AUC0-inf, Tmax, AUC_%Extrap_obs, Lambda-z and t1/2.Timepoint: Pre-dose (0.000), 1.500 h, 3.000 h, 6.000 h, 24.000 h, 48.000 h, 96.000 h, 168.000 h, 240.000 h, 336.000 h and 504.000 h