Breast Cancer, Breast Neoplasms, HER2-positive Breast Cancer, Stage II Breast Cancer, Stage IIIA Breast Cancer
Conditions
Keywords
trastuzumab, Herceptin
Brief summary
This is a Phase III, double-blind, randomized, multicenter study to compare the efficacy and to evaluate the safety and immunogenicity of TX05 (trastuzumab) with Herceptin® in subjects with HER2 positive early breast cancer.
Interventions
BIOLOGICALTX05 (trastuzumab)
8 mg/kg, 90 min IV infusion (Cycle 5), followed by 6 mg/kg, 60 min IV infusion (Cycles 6 - 8)
BIOLOGICALHerceptin®
8 mg/kg, 90 min IV infusion (Cycle 5), followed by 6 mg/kg, 60 min IV infusion (Cycles 6 - 8)
DRUGPaclitaxel
175 mg/m\^2, 60 min IV infusion, every 3 weeks (Cycles 5-8)
DRUGEpirubicin
75 mg/m\^2, IV bolus infusion, every 3 weeks (Cycles 1-4)
DRUGCyclophosphamide
600 mg/m\^2, 30 min IV infusion, every 3 weeks (Cycles 1-4)
Sponsors
Tanvex BioPharma USA, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Histologically confirmed HER 2 overexpressing invasive primary operable Stage II/IIIa breast cancer (AJCC version 7 staging criteria). * Available tumor tissue for central review of HER2 status. * Planned surgical resection of breast tumor. * Planned neoadjuvant chemotherapy. * Documentation of HER2 gene amplification or overexpression. * Ipsilateral, measurable tumor longest diameter \> 2 cm. * Known estrogen receptor (ER) and progesterone receptor (PR) hormone status (may be performed during screening). * ECOG performance status of 0 or 1. * Adequate bone marrow, hepatic and renal functions. * Left ventricular ejection fraction (LVEF) ≥ 50% or within institutional normal limits, measured by echocardiography or MUGA scan. * Effective contraception as defined by protocol. Key
Exclusion criteria
* Investigational therapy within 2 months of first dose of study drug. * Bilateral breast cancer. * Inflammatory breast cancer * Metastases. * Prior chemotherapy, biologic therapy, radiation or surgery for any active malignancy, including breast cancer. * Cardiac insufficiency, myocardial infarction, coronary/peripheral artery bypass graft, congestive heart failure, cerebrovascular accident, unstable angina pectoris, uncontrolled arrhythmia or pulmonary embolus within the previous 12 months prior to 1st administration of study drug. * Clinically significant active infection, poorly controlled diabetes mellitus and/or uncontrolled hypertension. * Major surgery, significant traumatic injury, radiation therapy and/or grade 3 hemorrhage within 4 weeks of 1st administration of study drug. * Pre-existing clinically significant Grade 2 peripheral neuropathy. * Malignancy within the last 5 years (except squamous/basal cell carcinoma of the skin, cervical carcinoma in situ and superficial bladder cancer). * Severe dyspnea at rest requiring oxygen therapy. * Known positive HIV, acute or chronic active infection with Hepatitis B or Hepatitis C. * Current pregnancy or breastfeeding. * Pre-existing thyroid abnormality with thyroid function that cannot be maintained in normal range despite optimal therapy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Subjects in Each Treatment Arm Who Achieve Pathologic Complete Response (pCR) | 3-7 weeks following last dose of study treatment | Pathologic complete response was determined by central review and defined as the absence of residual invasive cancer on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled lymph nodes following neoadjuvant systemic therapy (ypT0/Tis ypN0). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | End of Treatment (Week 24) or Early Termination Visit | Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Objective Response (ORR) = CR + PR. |
Countries
Belarus, Chile, Georgia, Hungary, India, Mexico, Peru, Philippines, Russia, Ukraine
Participant flow
Recruitment details
A total of 809 subjects were randomized to the study. Of these, 806 subjects initiated protocol treatment.
Pre-assignment details
Of the 806 subjects who initiated protocol treatment, 794 subjects initiated Cycle 5 (when trastuzumab was added); of these 394 subjects received TX05 and 400 subjects received Herceptin.
Participants by arm
| Arm | Count |
|---|---|
| TX05 (Trastuzumab) • Intravenous (IV) epirubicin, 75 mg/m\^2 and cyclophosphamide 600 mg/m2 every 3 weeks for 4 cycles
Followed by:
• IV TX05 8 mg/kg loading dose then 6 mg/kg and paclitaxel 175 mg/m2 every 3 weeks for 4 cycles
TX05 (trastuzumab): 8 mg/kg, 90 min IV infusion (Cycle 5), followed by 6 mg/kg, 60 min IV infusion (Cycles 6 - 8)
Paclitaxel: 175 mg/m\^2, 60 min IV infusion, every 3 weeks (Cycles 5-8)
Epirubicin: 75 mg/m\^2, IV bolus infusion, every 3 weeks (Cycles 1-4)
Cyclophosphamide: 600 mg/m\^2, 30 min IV infusion, every 3 weeks (Cycles 1-4) | 394 |
| Herceptin® • Intravenous (IV) epirubicin, 75 mg/m\^2 and cyclophosphamide 600 mg/m2 every 3 weeks for 4 cycles
Followed by:
• IV Herceptin 8 mg/kg loading dose then 6 mg/kg and paclitaxel 175 mg/m2 every 3 weeks for 4 cycles
Herceptin®: 8 mg/kg, 90 min IV infusion (Cycle 5), followed by 6 mg/kg, 60 min IV infusion (Cycles 6 - 8)
Paclitaxel: 175 mg/m\^2, 60 min IV infusion, every 3 weeks (Cycles 5-8)
Epirubicin: 75 mg/m\^2, IV bolus infusion, every 3 weeks (Cycles 1-4)
Cyclophosphamide: 600 mg/m\^2, 30 min IV infusion, every 3 weeks (Cycles 1-4) | 400 |
| Total | 794 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Discontinued Treatment after Cycle 5 due to Adverse Event | 0 | 1 |
| Overall Study | Discontinued Treatment after Cycle 5 due to Consent Withdrawn | 0 | 2 |
| Overall Study | Discontinued Treatment after Cycle 5 due to COVID-19 | 0 | 1 |
| Overall Study | Discontinued Treatment after Cycle 5 due to Death | 0 | 1 |
| Overall Study | Discontinued Treatment after Cycle 5 due to Other (Subject Decision) | 1 | 2 |
| Overall Study | Subjects Randomized that did not Treat | 3 | 0 |
| Overall Study | Subjects who Randomized and Treated but Drop prior to Cycle 5 | 7 | 5 |
Baseline characteristics
| Characteristic | Herceptin® | Total | TX05 (Trastuzumab) |
|---|---|---|---|
| Age, Continuous | 53.4 years STANDARD_DEVIATION 10.83 | 53.8 years STANDARD_DEVIATION 11.32 | 54.2 years STANDARD_DEVIATION 11.8 |
| ECOG Grade 0 | 305 Participants | 621 Participants | 316 Participants |
| ECOG Grade 1 | 95 Participants | 173 Participants | 78 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 71 Participants | 140 Participants | 69 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 328 Participants | 653 Participants | 325 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants |
| Hormone Receptor Status Negative | 146 Participants | 287 Participants | 141 Participants |
| Hormone Receptor Status Positive | 254 Participants | 507 Participants | 253 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 14 Participants | 29 Participants | 15 Participants |
| Race (NIH/OMB) Asian | 72 Participants | 136 Participants | 64 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 27 Participants | 50 Participants | 23 Participants |
| Race (NIH/OMB) White | 286 Participants | 578 Participants | 292 Participants |
| Sex: Female, Male Female | 400 Participants | 794 Participants | 394 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
| Tumor Stage IIA | 141 Participants | 283 Participants | 142 Participants |
| Tumor Stage IIB | 173 Participants | 342 Participants | 169 Participants |
| Tumor Stage IIIA | 86 Participants | 169 Participants | 83 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 394 | 1 / 400 |
| other Total, other adverse events | 246 / 394 | 250 / 400 |
| serious Total, serious adverse events | 11 / 394 | 9 / 400 |
Outcome results
Primary
Proportion of Subjects in Each Treatment Arm Who Achieve Pathologic Complete Response (pCR)
Pathologic complete response was determined by central review and defined as the absence of residual invasive cancer on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled lymph nodes following neoadjuvant systemic therapy (ypT0/Tis ypN0).
Time frame: 3-7 weeks following last dose of study treatment
Population: Per Protocol Population \[includes all subjects who received at least one dose of study drug (TX05 or Herceptin) and had no major protocol deviations that impact the efficacy endpoints\].
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TX05 (Trastuzumab) | Proportion of Subjects in Each Treatment Arm Who Achieve Pathologic Complete Response (pCR) | Subjects who do not Meet pCR Criteria | 172 participants |
| TX05 (Trastuzumab) | Proportion of Subjects in Each Treatment Arm Who Achieve Pathologic Complete Response (pCR) | Subjects Meeting pCR Criteria | 164 participants |
| Herceptin® | Proportion of Subjects in Each Treatment Arm Who Achieve Pathologic Complete Response (pCR) | Subjects who do not Meet pCR Criteria | 185 participants |
| Herceptin® | Proportion of Subjects in Each Treatment Arm Who Achieve Pathologic Complete Response (pCR) | Subjects Meeting pCR Criteria | 153 participants |
95% CI: [0.9185, 1.2659]
Secondary
Objective Response Rate (ORR)
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Objective Response (ORR) = CR + PR.
Time frame: End of Treatment (Week 24) or Early Termination Visit
Population: This analysis was performed on the modified intent-to-treat population. The modified intent-to-treat (mITT) population includes all subjects who were randomized and received at least 1 dose of TX05 or Herceptin.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| TX05 (Trastuzumab) | Objective Response Rate (ORR) | 332 Participants |
| Herceptin® | Objective Response Rate (ORR) | 340 Participants |