HER2-positive Breast Cancer, Early-stage Breast Cancer, Breast Cancer, Breast Neoplasms, Stage II Breast Cancer, Stage IIIA Breast Cancer
Conditions
Brief summary
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.
Interventions
BIOLOGICALTX05 (trastuzumab)
Subjects will receive up to 13 cycles of adjuvant treatment.
BIOLOGICALHerceptin (trastuzumab)
Subjects will receive up to 13 cycles of adjuvant treatment.
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
* 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Immunogenicity Assessments (ADA and Nab) | Assessed from first infusion through end of treatment (Week 45) or Early Termination visit. Each cycle is 3 weeks. | 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. |
| Disease-Free Survival | Through study completion/end of treatment (Week 45). | 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. |
| Overall Survival | Through study completion/end of treatment (Week 45). | OS, defined as the time from randomization in the neoadjuvant study (Protocol TX05-03) until death from any cause. |
Countries
Belarus, Chile, Georgia, Hungary, India, Mexico, Peru, Philippines, Russia, Ukraine
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Test Product (TX05 Only) 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. | 175 |
| Reference Therapy (Herceptin Only) 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 continued to receive Herceptin in this extension study. | 82 |
| Test Product (Herceptin/TX05 Transition) 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. | 81 |
| Total | 338 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 2 | 0 |
| Overall Study | Lack of Efficacy | 2 | 2 | 3 |
| Overall Study | Lost to Follow-up | 0 | 0 | 1 |
| Overall Study | Pregnancy | 1 | 0 | 0 |
| Overall Study | Subject refused to continue, AE and 2 patients only received 10 of 13 cycles | 3 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 0 | 0 |
Baseline characteristics
| Characteristic | Test Product (TX05 Only) | Total | Test Product (Herceptin/TX05 Transition) | Reference Therapy (Herceptin Only) |
|---|---|---|---|---|
| Age, Continuous | 55.3 years STANDARD_DEVIATION 11.43 | 54.6 years STANDARD_DEVIATION 10.95 | 54.0 years STANDARD_DEVIATION 10.71 | 53.7 years STANDARD_DEVIATION 10.12 |
| ECOG Grade 0 | 142 Participants | 262 Participants | 64 Participants | 56 Participants |
| ECOG Grade 1 | 29 Participants | 69 Participants | 16 Participants | 24 Participants |
| ECOG Grade 2 | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| ECOG Grade 3 | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| ECOG Grade 4 | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| ECOG Grade 5 | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| ECOG Missing | 4 Participants | 7 Participants | 1 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 29 Participants | 51 Participants | 10 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 146 Participants | 287 Participants | 71 Participants | 70 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Hormone Receptor Status Negative | 75 Participants | 140 Participants | 33 Participants | 32 Participants |
| Hormone Receptor Status Positive | 100 Participants | 198 Participants | 48 Participants | 50 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 5 Participants | 8 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 23 Participants | 53 Participants | 17 Participants | 13 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 11 Participants | 20 Participants | 5 Participants | 4 Participants |
| Race (NIH/OMB) White | 136 Participants | 257 Participants | 57 Participants | 64 Participants |
| Sex: Female, Male Female | 175 Participants | 338 Participants | 81 Participants | 82 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Tumor Stage Stage IIa | 65 Participants | 125 Participants | 32 Participants | 28 Participants |
| Tumor Stage Stage IIb | 78 Participants | 154 Participants | 35 Participants | 41 Participants |
| Tumor Stage Stage IIIa | 32 Participants | 59 Participants | 14 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 175 | 0 / 82 | 1 / 81 |
| other Total, other adverse events | 49 / 175 | 15 / 82 | 15 / 81 |
| serious Total, serious adverse events | 4 / 175 | 3 / 82 | 2 / 81 |
Outcome results
Primary
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.
Time frame: Through study completion/end of treatment (Week 45).
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Test Product (TX05 Only) | Disease-Free Survival | Recurrence of Breast Cancer or a Diagnosis of a Second Primary Cancer | 6 Participants |
| Test Product (TX05 Only) | Disease-Free Survival | No Post Baseline or No Evaluable Post Baseline | 1 Participants |
| Test Product (TX05 Only) | Disease-Free Survival | Discontinued form Study | 8 Participants |
| Test Product (TX05 Only) | Disease-Free Survival | Death | 0 Participants |
| Test Product (TX05 Only) | Disease-Free Survival | No Baseline or No Evaluable Baseline Assessment | 0 Participants |
| Test Product (TX05 Only) | Disease-Free Survival | No recurrence of Breast Cancer and No Diagnosis of a Second Primary Cancer | 160 Participants |
| Reference Therapy (Herceptin Only) | Disease-Free Survival | Discontinued form Study | 4 Participants |
| Reference Therapy (Herceptin Only) | Disease-Free Survival | Recurrence of Breast Cancer or a Diagnosis of a Second Primary Cancer | 5 Participants |
| Reference Therapy (Herceptin Only) | Disease-Free Survival | No recurrence of Breast Cancer and No Diagnosis of a Second Primary Cancer | 73 Participants |
| Reference Therapy (Herceptin Only) | Disease-Free Survival | Death | 0 Participants |
| Reference Therapy (Herceptin Only) | Disease-Free Survival | No Post Baseline or No Evaluable Post Baseline | 0 Participants |
| Reference Therapy (Herceptin Only) | Disease-Free Survival | No Baseline or No Evaluable Baseline Assessment | 0 Participants |
| Test Product (Herceptin/TX05 Transition) | Disease-Free Survival | No Baseline or No Evaluable Baseline Assessment | 0 Participants |
| Test Product (Herceptin/TX05 Transition) | Disease-Free Survival | No Post Baseline or No Evaluable Post Baseline | 0 Participants |
| Test Product (Herceptin/TX05 Transition) | Disease-Free Survival | Recurrence of Breast Cancer or a Diagnosis of a Second Primary Cancer | 3 Participants |
| Test Product (Herceptin/TX05 Transition) | Disease-Free Survival | Death | 0 Participants |
| Test Product (Herceptin/TX05 Transition) | Disease-Free Survival | Discontinued form Study | 2 Participants |
| Test Product (Herceptin/TX05 Transition) | Disease-Free Survival | No recurrence of Breast Cancer and No Diagnosis of a Second Primary Cancer | 76 Participants |
Primary
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.
Time frame: Assessed from first infusion through end of treatment (Week 45) or Early Termination visit. Each cycle is 3 weeks.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Test Product (TX05 Only) | Immunogenicity Assessments (ADA and Nab) | Baseline | Nab Positive | 0 Participants |
| Test Product (TX05 Only) | Immunogenicity Assessments (ADA and Nab) | End of Study/Early Terminiation | Nab Positive | 0 Participants |
| Test Product (TX05 Only) | Immunogenicity Assessments (ADA and Nab) | Cycle 6 Week 15 | Nab Positive | 0 Participants |
| Test Product (TX05 Only) | Immunogenicity Assessments (ADA and Nab) | End of Study/Early Terminiation | ADA Negative | 146 Participants |
| Test Product (TX05 Only) | Immunogenicity Assessments (ADA and Nab) | Baseline | ADA Negative | 159 Participants |
| Test Product (TX05 Only) | Immunogenicity Assessments (ADA and Nab) | End of Study/Early Terminiation | Not evaluated | 25 Participants |
| Test Product (TX05 Only) | Immunogenicity Assessments (ADA and Nab) | Baseline | ADA Positive | 3 Participants |
| Test Product (TX05 Only) | Immunogenicity Assessments (ADA and Nab) | Baseline | Not evaluated | 13 Participants |
| Test Product (TX05 Only) | Immunogenicity Assessments (ADA and Nab) | Cycle 6 Week 15 | ADA Positive | 1 Participants |
| Test Product (TX05 Only) | Immunogenicity Assessments (ADA and Nab) | Cycle 6 Week 15 | ADA Negative | 164 Participants |
| Test Product (TX05 Only) | Immunogenicity Assessments (ADA and Nab) | Cycle 6 Week 15 | Not evaluated | 10 Participants |
| Test Product (TX05 Only) | Immunogenicity Assessments (ADA and Nab) | End of Study/Early Terminiation | ADA Positive | 4 Participants |
| Reference Therapy (Herceptin Only) | Immunogenicity Assessments (ADA and Nab) | Cycle 6 Week 15 | Not evaluated | 7 Participants |
| Reference Therapy (Herceptin Only) | Immunogenicity Assessments (ADA and Nab) | End of Study/Early Terminiation | ADA Positive | 1 Participants |
| Reference Therapy (Herceptin Only) | Immunogenicity Assessments (ADA and Nab) | Baseline | Nab Positive | 0 Participants |
| Reference Therapy (Herceptin Only) | Immunogenicity Assessments (ADA and Nab) | Cycle 6 Week 15 | ADA Negative | 74 Participants |
| Reference Therapy (Herceptin Only) | Immunogenicity Assessments (ADA and Nab) | End of Study/Early Terminiation | Nab Positive | 0 Participants |
| Reference Therapy (Herceptin Only) | Immunogenicity Assessments (ADA and Nab) | Baseline | Not evaluated | 3 Participants |
| Reference Therapy (Herceptin Only) | Immunogenicity Assessments (ADA and Nab) | Baseline | ADA Positive | 2 Participants |
| Reference Therapy (Herceptin Only) | Immunogenicity Assessments (ADA and Nab) | End of Study/Early Terminiation | ADA Negative | 75 Participants |
| Reference Therapy (Herceptin Only) | Immunogenicity Assessments (ADA and Nab) | Cycle 6 Week 15 | Nab Positive | 0 Participants |
| Reference Therapy (Herceptin Only) | Immunogenicity Assessments (ADA and Nab) | Cycle 6 Week 15 | ADA Positive | 1 Participants |
| Reference Therapy (Herceptin Only) | Immunogenicity Assessments (ADA and Nab) | End of Study/Early Terminiation | Not evaluated | 6 Participants |
| Reference Therapy (Herceptin Only) | Immunogenicity Assessments (ADA and Nab) | Baseline | ADA Negative | 77 Participants |
| Test Product (Herceptin/TX05 Transition) | Immunogenicity Assessments (ADA and Nab) | End of Study/Early Terminiation | Not evaluated | 8 Participants |
| Test Product (Herceptin/TX05 Transition) | Immunogenicity Assessments (ADA and Nab) | Cycle 6 Week 15 | Nab Positive | 0 Participants |
| Test Product (Herceptin/TX05 Transition) | Immunogenicity Assessments (ADA and Nab) | Baseline | ADA Positive | 3 Participants |
| Test Product (Herceptin/TX05 Transition) | Immunogenicity Assessments (ADA and Nab) | Baseline | Nab Positive | 0 Participants |
| Test Product (Herceptin/TX05 Transition) | Immunogenicity Assessments (ADA and Nab) | Baseline | ADA Negative | 74 Participants |
| Test Product (Herceptin/TX05 Transition) | Immunogenicity Assessments (ADA and Nab) | Baseline | Not evaluated | 4 Participants |
| Test Product (Herceptin/TX05 Transition) | Immunogenicity Assessments (ADA and Nab) | Cycle 6 Week 15 | ADA Negative | 74 Participants |
| Test Product (Herceptin/TX05 Transition) | Immunogenicity Assessments (ADA and Nab) | Cycle 6 Week 15 | Not evaluated | 3 Participants |
| Test Product (Herceptin/TX05 Transition) | Immunogenicity Assessments (ADA and Nab) | End of Study/Early Terminiation | ADA Positive | 2 Participants |
| Test Product (Herceptin/TX05 Transition) | Immunogenicity Assessments (ADA and Nab) | End of Study/Early Terminiation | Nab Positive | 0 Participants |
| Test Product (Herceptin/TX05 Transition) | Immunogenicity Assessments (ADA and Nab) | End of Study/Early Terminiation | ADA Negative | 71 Participants |
| Test Product (Herceptin/TX05 Transition) | Immunogenicity Assessments (ADA and Nab) | Cycle 6 Week 15 | ADA Positive | 4 Participants |
Primary
Overall Survival
OS, defined as the time from randomization in the neoadjuvant study (Protocol TX05-03) until death from any cause.
Time frame: Through study completion/end of treatment (Week 45).
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Test Product (TX05 Only) | Overall Survival | Lost to Follow-Up | 0 Participants |
| Test Product (TX05 Only) | Overall Survival | Last known alive | 175 Participants |
| Test Product (TX05 Only) | Overall Survival | Death | 0 Participants |
| Reference Therapy (Herceptin Only) | Overall Survival | Lost to Follow-Up | 0 Participants |
| Reference Therapy (Herceptin Only) | Overall Survival | Last known alive | 82 Participants |
| Reference Therapy (Herceptin Only) | Overall Survival | Death | 0 Participants |
| Test Product (Herceptin/TX05 Transition) | Overall Survival | Last known alive | 80 Participants |
| Test Product (Herceptin/TX05 Transition) | Overall Survival | Death | 1 Participants |
| Test Product (Herceptin/TX05 Transition) | Overall Survival | Lost to Follow-Up | 0 Participants |