Extension Study to Provide Adjuvant Treatment Following Neoadjuvant Treatment and Surgical Resection in Protocol TX05-03

Study Overview
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Brief Summary
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This is an extension study to provide adjuvant treatment with single agent Herceptin or TX05 and assess continued safety and immunogenicity in subjects with HER2-positive early breast cancer following neoadjuvant treatment and surgical resection in Protocol TX05-03.

Official Title
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A Double-blinded Extension Study to Provide Adjuvant Treatment With Single Agent Herceptin® or TX05 and Assess Continued Safety and Immunogenicity in Subjects With HER2-positive Early Breast Cancer Following Neoadjuvant Treatment and Surgical Resection in Protocol TX05-03

Conditions
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HER2-positive Breast Cancer, Early-stage Breast Cancer, Breast Cancer, Breast Neoplasms, Stage II Breast Cancer, Stage IIIA Breast Cancer

Intervention / Treatment
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* Biological: TX05 (trastuzumab)
* Biological: Herceptin (trastuzumab)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed written informed consent. Females ≥ 18 years of age. Completed neoadjuvant treatment (regardless of treatment arm) in the TX05/ Herceptin neoadjuvant study and the investigator believes the subject requires continued access to single agent trastuzumab in order to continue deriving clinical benefit. Successfully undergone surgical resection of their primary tumor with no evidence of residual disease (as determined by local assessment) and no other adjuvant therapy, other than trastuzumab, is planned. However, subjects will be allowed to receive hormonal therapy if they have hormone receptor positive tumors. Subjects will also be allowed to receive adjuvant radiation therapy, if required by their treating physician. Able to comply with the study protocol. Female subjects of childbearing potential must have a negative serum pregnancy test within 14 days of first administration of study drug and agree to use effective contraception (hormonal contraceptive, intrauterine device, diaphragm with spermicide, or condom with spermicide) throughout the study period and for 7 months after last administration of study drug. Exclusion Criteria: Breast cancer metastases or residual disease post operatively (as determined by local assessment). History or presence of a medical condition or disease that in the investigator's opinion would place the subject at an unacceptable risk for study participation. Lactating or pregnant female. Women of childbearing potential who do not consent to use highly effective methods of birth control (e.g. true abstinence [periodic abstinence {e.g. calendar ovulation, symptothermal, post-ovulation methods} and withdrawal are not acceptable methods of contraception], sterilization, or other non-hormonal forms of contraception) during treatment and for at least 7 months after the last administration of study drug. Subjects must agree to not breast-feed while receiving study drug. Any condition that in the opinion of the Investigator represents an obstacle for study conduct and/or represents a potential unacceptable risk for subjects.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Test Product (TX05)<br>IV trastuzumab (TX05) 8 mg/kg loading dose and then 6 mg/kg every 3 weeks for up to 13 cycles TX05 (trastuzumab): Subjects will receive up to 13 cycles of adjuvant treatment. These subjects received TX05 on the TX05-03 study and continued to receive TX05 in this extension study. | Biological: TX05 (trastuzumab)<br>* Subjects will receive up to 13 cycles of adjuvant treatment.<br>|
| Active Comparator: Reference Therapy (Herceptin)<br>IV trastuzumab (Herceptin) TX05 8 mg/kg loading dose and then 6 mg/kg every 3 weeks for up to 13 cycles Herceptin (trastuzumab): Subjects will receive up to 13 cycles of adjuvant treatment. These subjects received Herceptin on the TX05-03 study and were randomized to receive Herceptin in this extension study. | Biological: Herceptin (trastuzumab)<br>* Subjects will receive up to 13 cycles of adjuvant treatment.<br>|
| Experimental: Test Product (Herceptin/TX05 Transition)<br>IV trastuzumab (TX05) 8 mg/kg loading dose and then 6 mg/kg every 3 weeks for up to 13 cycles TX05 (trastuzumab): Subjects will receive up to 13 cycles of adjuvant treatment. These subjects received Herceptin on the TX05-03 study and were randomized to receive TX05 in this extension study. | Biological: TX05 (trastuzumab)<br>* Subjects will receive up to 13 cycles of adjuvant treatment.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immunogenicity Assessments (ADA and Nab) | Samples for the evaluation of anti-drug antibodies (ADA), including neutralizing antibodies (Nab) were obtained before the administration of Cycle 1 (Week 0), Cycle 6 (Week 15), and the EOT/ET Visit. Only subjects with a positive ADA result were further tested for ADA cross-reactivity and Nab. Only subjects with a positive Nab result were further tested for Nab cross-reactivity. | Assessed from first infusion through end of treatment (Week 45) or Early Termination visit. Each cycle is 3 weeks. | 
| Disease-Free Survival | DFS, defined as the time from randomization in the neoadjuvant study (Protocol TX05-03) to the documentation of a first failure, where a failure was the recurrence of breast cancer or a diagnosis of a second primary cancer. | Through study completion/end of treatment (Week 45). | 
| Overall Survival | OS, defined as the time from randomization in the neoadjuvant study (Protocol TX05-03) until death from any cause. | Through study completion/end of treatment (Week 45). |