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This study will evaluate the pharmacokinetics, efficacy, and safety of the pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) as compared with those of the pertuzumab intravenous (IV) and trastuzumab IV formulations in Chinese participants with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Active Comparator | Participants will receive 8 cycles of neoadjuvant chemotherapy: 4 cycles of doxorubicin plus cyclophosphamide (AC) once every 3 weeks (Q3W) followed by docetaxel Q3W for 4 cycles. Pertuzumab and trastuzumab will be given intravenously (IV) for 4 cycles Q3W concurrently with the taxane component of chemotherapy. After completing their neoadjuvant therapy, participants will undergo surgery. Thereafter, participants will receive an additional 14 cycles of pertuzumab IV and trastuzumab IV for a total of 18 cycles. |
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| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Experimental | Participants will receive 8 cycles of neoadjuvant chemotherapy: 4 cycles of AC Q3W followed by docetaxel Q3W for 4 cycles. The pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) will be given subcutaneously (SC) for 4 cycles (Q3W) concurrently with the taxane component of chemotherapy. After completing their neoadjuvant therapy, participants will undergo surgery. Thereafter, participants will receive an additional 14 cycles of the PH FDC SC for a total of 18 cycles. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Pertuzumab IV | Drug | Pertuzumab will be administered as a fixed non-weight-based loading dose of 840-milligrams (mg) IV and then a 420-mg IV maintenance dose Q3W. |
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| Measure | Description | Time Frame |
|---|---|---|
| Serum Trough Concentration (Ctrough) of Pertuzumab During Cycle 7 (Pre-Dose Cycle 8) | The observed pertuzumab trough serum concentration (Ctrough) at Cycle 7 was assessed following 3 cycles of pertuzumab IV and trastuzumab IV or the fixed-dose combination (FDC) of pertuzumab and trastuzumab SC. The Per Protocol Pharmacokinetics (PK) analysis population includes all enrolled participants who adhered to the protocol. Exclusions from the Per Protocol PK analysis population were made for the following reasons: participants were missing the Ctrough pre-dose Cycle 8 PK sample, participants with a Ctrough sample collected with at least 2 days deviation from the planned date on Day 21 (i.e., before Day 19 or after Day 23), participants given a dose amount that deviated from the planned dose by >20% within 3 cycles (from Cycle 5), participants with a dose delay of more than 7 days, a Cycle 7 subcutaneous injection site other than thigh was used, if the Cycle 8 IV pre-dose and post-dose PK samples were switched, and an assay error impacting Ctrough measurement. | Pre-dose at Cycle 8 (one cycle is 21 days) |
| Serum Ctrough of Trastuzumab During Cycle 7 (Pre-Dose Cycle 8) | The observed trastuzumab trough serum concentration (Ctrough) at Cycle 7 was assessed following 3 cycles of pertuzumab IV and trastuzumab IV or the fixed-dose combination (FDC) of pertuzumab and trastuzumab SC. The Per Protocol Pharmacokinetics (PK) analysis population includes all enrolled participants who adhered to the protocol. Exclusions from the Per Protocol PK analysis population were made for the following reasons: participants were missing the Ctrough pre-dose Cycle 8 PK sample, participants with a Ctrough sample collected with at least 2 days deviation from the planned date on Day 21 (i.e., before Day 19 or after Day 23), participants given a dose amount that deviated from the planned dose by >20% within 3 cycles (from Cycle 5), participants with a dose delay of more than 7 days, a Cycle 7 subcutaneous injection site other than thigh was used, if the Cycle 8 IV pre-dose and post-dose PK samples were switched, and an assay error impacting Ctrough measurement. | Pre-dose at Cycle 8 (one cycle is 21 days) |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants With Total Pathological Complete Response (tpCR), According to Local Pathologist Assessment | Total pathological complete response (tpCR) was defined as eradication of invasive disease in the breast and axilla; that is, ypT0/is ypN0, according to the local pathologists' assessment. Pathologic response to therapy was determined at the time of surgery. The tpCR rate is the percentage of participants in the ITT population who achieved a tpCR. Participants with missing data for tpCR (i.e., do not undergo surgery or have an invalid pCR assessment) were included in the analysis and classified as non-responders. Rates of tpCR were calculated in each treatment arm and were assessed using the difference between the Arm B: Pertuzumab and Trastuzumab FDC SC and the Arm A: Pertuzumab IV and Trastuzumab IV tpCR rates and corresponding 95% Clopper-Pearson confidence intervals (CIs). The difference between the tpCR rates along with corresponding 95% Hauck-Anderson CIs were calculated. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Clinical Trials | Hoffmann-La Roche | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Peking University People's Hospital | Beijing | 100044 | China | |||
| Beijing Cancer Hospital |
For eligible studies, qualified researchers may request access to individual patient level clinical data. See Roche's commitment to transparency of clinical study information here: https://go.roche.com/data\_sharing
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Participants with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer, who were candidates for preoperative neoadjuvant treatment in the clinical practice, were enrolled in the study.
Participants were enrolled at 18 investigational sites in China.
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| ID | Title | Description |
|---|---|---|
| FG000 | Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Participants received 8 cycles of neoadjuvant chemotherapy: 4 cycles of doxorubicin plus cyclophosphamide (AC) once every 3 weeks (Q3W) followed by docetaxel Q3W for 4 cycles. Pertuzumab and trastuzumab were given intravenously (IV) for 4 cycles Q3W concurrently with the taxane component of chemotherapy. After completing their neoadjuvant therapy, participants underwent surgery. Thereafter, participants received an additional 14 cycles of pertuzumab IV and trastuzumab IV for a total of 18 cycles. |
| Title | Milestones | Reasons Not Completed | ||||
|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jul 28, 2020 | Dec 6, 2022 |
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| Trastuzumab IV | Drug | Trastuzumab will be administered as an 8-milligram per kilogram of body weight (mg/kg) IV loading dose and then 6 mg/kg IV maintenance dose Q3W. |
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| Pertuzumab and Trastuzumab FDC SC | Drug | The pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) will be administered SC at a fixed non-weight-based dose. A loading dose of 1200 mg SC pertuzumab and 600 mg SC trastuzumab is then followed by a maintenance dose of 600 mg SC pertuzumab and 600 mg SC trastuzumab Q3W. |
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| Doxorubicin | Drug | Doxorubicin 60 milligrams per meter squared of body surface area (mg/m^2) will be administered IV on Day 1 of each cycle of treatment (as part of AC Q3W) for Cycles 1-4. |
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| Cyclophosphamide | Drug | Cyclophosphamide 600 mg/m^2 will be administered IV on Day 1 of each cycle of treatment (as part of AC Q3W) for Cycles 1-4. |
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| Docetaxel | Drug | Docetaxel 75 mg/m^2 will be administered IV on Day 1 of Cycle 5. At the investigator's discretion the dose may be escalated to 100 mg/m^2 IV for Cycles 6-8 (Q3W) provided no dose-limiting toxicity occurs. |
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| Surgery | Procedure | Participants in both cohorts are scheduled to undergo surgery after 8 cycles of neoadjuvant therapy. Participants may undergo breast-conserving surgery or mastectomy according to routine clinical practice. |
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| Post-Operative Radiotherapy | Radiation | If indicated, radiotherapy is given after chemotherapy and surgery, during adjuvant HER2-targeted therapy and hormone therapy (for hormone-receptor positive disease). |
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| Hormone Therapy | Drug | For hormone receptor positive breast cancer, tamoxifen or aromatase inhibitors will be allowed as adjuvant hormone therapy for postmenopausal participants and with ovarian suppression or ablation for premenopausal participants in countries where it has been registered for this indication. Its use must be consistent with the registered label. Hormone therapy is given after chemotherapy and surgery during adjuvant HER2-targeted therapy. |
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| Following completion of surgery (up to 33 weeks) |
| Kaplan-Meier Estimate of the Percentage of Participants Who Are Event-Free According to Invasive Disease-Free Survival (iDFS; Excluding Second Primary Non-Breast Cancer [SPNBC]) Criteria | iDFS (excluding SPNBC) is defined as the time from the first date of no disease (i.e., the date of primary surgery) to the first occurrence of one of the following events: ipsilateral invasive breast tumor recurrence; ipsilateral local-regional invasive breast cancer reccurrence; distant recurrence; contralateral invasive breast cancer; or death attributable to any cause. Ipsilateral or contralateral in situ disease and SPNBC (including in situ carcinomas and non-melanoma skin cancers) will not be counted as progressive disease or relapse. | From date of surgery to iDFS (excluding SPNBC) event (up to 5 years) |
| Kaplan-Meier Estimate of the Percentage of Participants Who Are Event-Free According to iDFS (Including SPNBC) Criteria | iDFS including SPNBC is defined in the same way as iDFS but including SPNBC as an event (with the exception of non-melanoma skin cancers and in situ carcinoma of any site). | From date of surgery to iDFS (including SPNBC) event (up to 5 years) |
| Kaplan-Meier Estimate of the Percentage of Participants Who Are Event-Free According to Event-Free Survival (EFS; Excluding SPNBC) Criteria | EFS (excluding SPNBC) is defined as the time from enrollment to the first occurrence of one of the following events: breast cancer progression; breast cancer recurrence; or death from any cause. Ipsilateral or contralateral in situ disease and SPNBC (including in situ carcinomas and non-melanoma skin cancers) will not be counted as progressive disease or relapse. | From baseline to EFS (excluding SPNBC) event (up to 5.5 years) |
| Kaplan-Meier Estimate of the Percentage of Participants Who Are Event-Free According to EFS (Including SPNBC) Criteria | EFS including SPNBC is defined in the same way as EFS, but including SPNBC as an event (with the exception of non-melanoma skin cancers and in situ carcinoma of any site). | From baseline to EFS (including SPNBC) event (up to 5.5 years) |
| Kaplan-Meier Estimate of the Percentage of Participants Who Are Event-Free According to Distant Recurrence-Free Interval (DRFI) Criteria | DRFI is defined as the time between randomization and the date of distant breast cancer recurrence. | From baseline to DFRI event (up to 5.5 years) |
| Kaplan-Meier Estimate of the Percentage of Participants in Overall Survival | From baseline to death from any cause (up to 5.5 years) |
| Number of Participants With at Least One Adverse Event by Severity, Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 4 (NCI CTCAE v4) | From baseline until study completion (up to 5.5 years) |
| Number of Participants With a Primary Cardiac Event | A primary cardiac event is defined as either a symptomatic ejection fraction decrease (heart failure) of New York Heart Association (NYHA) Class III/IV and a drop in left ventricular ejection fraction (LVEF) of at least 10-percentage points from baseline and to below 50%, or a definite or probable cardiac death. NYHA Class III is defined as: marked limitation of physical activity; comfortable at rest, but less than ordinary activity causes fatigue, palpitation, or dyspnea. NYHA Class IV is defined as: Inability to carry on any physical activity without discomfort; symptoms of cardiac insufficiency at rest; if any physical activity is undertaken, discomfort is increased. Definite cardiac death is defined as death due to heart failure, myocardial infarction, or documented primary arrhythmia. Probable cardiac death is defined as sudden unexpected death within 24 hours of a definite or probable cardiac event (e.g., syncope, cardiac arrest, chest pain, etc.) without documented etiology. | From baseline until study completion (up to 5.5 years) |
| Number of Participants With a Secondary Cardiac Event, Defined as an Asymptomatic or Mildly Symptomatic Left Ventricular Systolic Dysfunction (LVSD) of NYHA Class II | An LVSD ("Ejection fraction decreased") of NYHA Class II is defined as a left ventricular ejection fraction (LVEF) decrease of ≥10-percentage points below the baseline measurement to an absolute LVEF value of <50%, confirmed by a second LVEF assessment within approximately 3 weeks also showing a documented drop. | From baseline until study completion (up to 5.5 years) |
| Beijing |
| 100142 |
| China |
| Jilin Cancer Hospital | Changchun | 130012 | China |
| The First Hospital of Jilin University | Changchun | 130021 | China |
| West China Hospital, Sichuan University | Chengdu | 610041 | China |
| The 900th Hospital of PLA joint service support force | Fuzhou | 110016 | China |
| Sun Yet-sen University Cancer Center | Guangzhou | 510060 | China |
| Zhejiang Cancer Hospital | Hangzhou | 310022 | China |
| Harbin Medical University Cancer Hospital | Harbin | 150081 | China |
| Shandong Cancer Hospital | Jinan | 250117 | China |
| Jiangsu Province Hospital | Nanjing | 210036 | China |
| The Affiliated Hospital of Medical College Qingdao University | Qingdao | 266003 | China |
| Ruijin Hospital, Shanghai Jiaotong University School of Medicine | Shanghai | 200025 | China |
| Fudan University Shanghai Cancer Center | Shanghai | 200032 | China |
| Hebei Medical University Fourth Hospital | Shijiazhuang | 050035 | China |
| Union Hospital Tongji Medical College Huazhong University of Science and Technology | Wuhan | 430023 | China |
| Hubei Cancer Hospital | Wuhan | 430079 | China |
| The First Affiliated Hospital of Xian Jiao Tong University | Xi'an | 710061 | China |
| FG001 | Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Participants received 8 cycles of neoadjuvant chemotherapy: 4 cycles of AC Q3W followed by docetaxel Q3W for 4 cycles. The pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) were given subcutaneously (SC) for 4 cycles (Q3W) concurrently with the taxane component of chemotherapy. After completing their neoadjuvant therapy, participants underwent surgery. Thereafter, participants received an additional 14 cycles of the PH FDC SC for a total of 18 cycles. |
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| Completed Neoadjuvant Treatment (24 Weeks) |
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| Completed Surgery (<9 Weeks) |
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| Started Adjuvant Treatment |
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| Completed Adjuvant Treatment (42 Weeks) |
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| Started Follow-Up (≥3 Years) | Participants who completed treatment or prematurely withdrew from treatment entered the follow-up phase. |
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| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Participants received 8 cycles of neoadjuvant chemotherapy: 4 cycles of doxorubicin plus cyclophosphamide (AC) once every 3 weeks (Q3W) followed by docetaxel Q3W for 4 cycles. Pertuzumab and trastuzumab were given intravenously (IV) for 4 cycles Q3W concurrently with the taxane component of chemotherapy. After completing their neoadjuvant therapy, participants underwent surgery. Thereafter, participants received an additional 14 cycles of pertuzumab IV and trastuzumab IV for a total of 18 cycles. |
| BG001 | Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Participants received 8 cycles of neoadjuvant chemotherapy: 4 cycles of AC Q3W followed by docetaxel Q3W for 4 cycles. The pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) were given subcutaneously (SC) for 4 cycles (Q3W) concurrently with the taxane component of chemotherapy. After completing their neoadjuvant therapy, participants underwent surgery. Thereafter, participants received an additional 14 cycles of the PH FDC SC for a total of 18 cycles. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | Years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
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| Randomization Stratification Factors: Hormone Receptor Status | Hormone receptor status was based on central assessment of participant samples for estrogen receptor (ER) and progesterone receptor (PgR) negativity or positivity. | Count of Participants | Participants |
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| Randomization Stratification Factors: Clinical Stage at Presentation | Breast cancer stages range from 0 to IV with IV being the most advanced stage, which is considered a worse outcome. Stages II and III are both invasive breast cancer stages and are subdivided into IIA, IIB, IIIA, IIIB and IIIC based on tumor size, presence and number of metastases in regional lymph nodes and presence of distant metastases. Participants enrolling in this study were categorized into stages II-IIIA and IIIB-IIIC with IIIC being considered the worst stage. | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Serum Trough Concentration (Ctrough) of Pertuzumab During Cycle 7 (Pre-Dose Cycle 8) | The observed pertuzumab trough serum concentration (Ctrough) at Cycle 7 was assessed following 3 cycles of pertuzumab IV and trastuzumab IV or the fixed-dose combination (FDC) of pertuzumab and trastuzumab SC. The Per Protocol Pharmacokinetics (PK) analysis population includes all enrolled participants who adhered to the protocol. Exclusions from the Per Protocol PK analysis population were made for the following reasons: participants were missing the Ctrough pre-dose Cycle 8 PK sample, participants with a Ctrough sample collected with at least 2 days deviation from the planned date on Day 21 (i.e., before Day 19 or after Day 23), participants given a dose amount that deviated from the planned dose by >20% within 3 cycles (from Cycle 5), participants with a dose delay of more than 7 days, a Cycle 7 subcutaneous injection site other than thigh was used, if the Cycle 8 IV pre-dose and post-dose PK samples were switched, and an assay error impacting Ctrough measurement. | Pertuzumab Per Protocol PK Population: includes only participants who adhered to the pre-specified criteria for the schedule of pharmacokinetic assessments. | Posted | Geometric Mean | Geometric Coefficient of Variation | micrograms per millilitre (μg/mL) | Pre-dose at Cycle 8 (one cycle is 21 days) |
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| Primary | Serum Ctrough of Trastuzumab During Cycle 7 (Pre-Dose Cycle 8) | The observed trastuzumab trough serum concentration (Ctrough) at Cycle 7 was assessed following 3 cycles of pertuzumab IV and trastuzumab IV or the fixed-dose combination (FDC) of pertuzumab and trastuzumab SC. The Per Protocol Pharmacokinetics (PK) analysis population includes all enrolled participants who adhered to the protocol. Exclusions from the Per Protocol PK analysis population were made for the following reasons: participants were missing the Ctrough pre-dose Cycle 8 PK sample, participants with a Ctrough sample collected with at least 2 days deviation from the planned date on Day 21 (i.e., before Day 19 or after Day 23), participants given a dose amount that deviated from the planned dose by >20% within 3 cycles (from Cycle 5), participants with a dose delay of more than 7 days, a Cycle 7 subcutaneous injection site other than thigh was used, if the Cycle 8 IV pre-dose and post-dose PK samples were switched, and an assay error impacting Ctrough measurement. | Trastuzumab Per Protocol PK Population: includes only participants who adhered to the pre-specified criteria for the schedule of pharmacokinetic assessments. | Posted | Geometric Mean | Geometric Coefficient of Variation | micrograms per milllilitre (μg/mL) | Pre-dose at Cycle 8 (one cycle is 21 days) |
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| Secondary | Percentage of Participants With Total Pathological Complete Response (tpCR), According to Local Pathologist Assessment | Total pathological complete response (tpCR) was defined as eradication of invasive disease in the breast and axilla; that is, ypT0/is ypN0, according to the local pathologists' assessment. Pathologic response to therapy was determined at the time of surgery. The tpCR rate is the percentage of participants in the ITT population who achieved a tpCR. Participants with missing data for tpCR (i.e., do not undergo surgery or have an invalid pCR assessment) were included in the analysis and classified as non-responders. Rates of tpCR were calculated in each treatment arm and were assessed using the difference between the Arm B: Pertuzumab and Trastuzumab FDC SC and the Arm A: Pertuzumab IV and Trastuzumab IV tpCR rates and corresponding 95% Clopper-Pearson confidence intervals (CIs). The difference between the tpCR rates along with corresponding 95% Hauck-Anderson CIs were calculated. | ITT Population: includes all enrolled participants. | Posted | Number | 95% Confidence Interval | percentage of participants | Following completion of surgery (up to 33 weeks) |
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| Secondary | Kaplan-Meier Estimate of the Percentage of Participants Who Are Event-Free According to Invasive Disease-Free Survival (iDFS; Excluding Second Primary Non-Breast Cancer [SPNBC]) Criteria | iDFS (excluding SPNBC) is defined as the time from the first date of no disease (i.e., the date of primary surgery) to the first occurrence of one of the following events: ipsilateral invasive breast tumor recurrence; ipsilateral local-regional invasive breast cancer reccurrence; distant recurrence; contralateral invasive breast cancer; or death attributable to any cause. Ipsilateral or contralateral in situ disease and SPNBC (including in situ carcinomas and non-melanoma skin cancers) will not be counted as progressive disease or relapse. | Not Posted | Feb 2027 | From date of surgery to iDFS (excluding SPNBC) event (up to 5 years) | Participants | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Kaplan-Meier Estimate of the Percentage of Participants Who Are Event-Free According to iDFS (Including SPNBC) Criteria | iDFS including SPNBC is defined in the same way as iDFS but including SPNBC as an event (with the exception of non-melanoma skin cancers and in situ carcinoma of any site). | Not Posted | Feb 2027 | From date of surgery to iDFS (including SPNBC) event (up to 5 years) | Participants | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Kaplan-Meier Estimate of the Percentage of Participants Who Are Event-Free According to Event-Free Survival (EFS; Excluding SPNBC) Criteria | EFS (excluding SPNBC) is defined as the time from enrollment to the first occurrence of one of the following events: breast cancer progression; breast cancer recurrence; or death from any cause. Ipsilateral or contralateral in situ disease and SPNBC (including in situ carcinomas and non-melanoma skin cancers) will not be counted as progressive disease or relapse. | Not Posted | Feb 2027 | From baseline to EFS (excluding SPNBC) event (up to 5.5 years) | Participants | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Kaplan-Meier Estimate of the Percentage of Participants Who Are Event-Free According to EFS (Including SPNBC) Criteria | EFS including SPNBC is defined in the same way as EFS, but including SPNBC as an event (with the exception of non-melanoma skin cancers and in situ carcinoma of any site). | Not Posted | Feb 2027 | From baseline to EFS (including SPNBC) event (up to 5.5 years) | Participants | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Kaplan-Meier Estimate of the Percentage of Participants Who Are Event-Free According to Distant Recurrence-Free Interval (DRFI) Criteria | DRFI is defined as the time between randomization and the date of distant breast cancer recurrence. | Not Posted | Feb 2027 | From baseline to DFRI event (up to 5.5 years) | Participants | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Kaplan-Meier Estimate of the Percentage of Participants in Overall Survival | Not Posted | Feb 2027 | From baseline to death from any cause (up to 5.5 years) | Participants | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Number of Participants With at Least One Adverse Event by Severity, Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 4 (NCI CTCAE v4) | Not Posted | Feb 2027 | From baseline until study completion (up to 5.5 years) | Participants | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Number of Participants With a Primary Cardiac Event | A primary cardiac event is defined as either a symptomatic ejection fraction decrease (heart failure) of New York Heart Association (NYHA) Class III/IV and a drop in left ventricular ejection fraction (LVEF) of at least 10-percentage points from baseline and to below 50%, or a definite or probable cardiac death. NYHA Class III is defined as: marked limitation of physical activity; comfortable at rest, but less than ordinary activity causes fatigue, palpitation, or dyspnea. NYHA Class IV is defined as: Inability to carry on any physical activity without discomfort; symptoms of cardiac insufficiency at rest; if any physical activity is undertaken, discomfort is increased. Definite cardiac death is defined as death due to heart failure, myocardial infarction, or documented primary arrhythmia. Probable cardiac death is defined as sudden unexpected death within 24 hours of a definite or probable cardiac event (e.g., syncope, cardiac arrest, chest pain, etc.) without documented etiology. | Not Posted | Feb 2027 | From baseline until study completion (up to 5.5 years) | Participants | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Number of Participants With a Secondary Cardiac Event, Defined as an Asymptomatic or Mildly Symptomatic Left Ventricular Systolic Dysfunction (LVSD) of NYHA Class II | An LVSD ("Ejection fraction decreased") of NYHA Class II is defined as a left ventricular ejection fraction (LVEF) decrease of ≥10-percentage points below the baseline measurement to an absolute LVEF value of <50%, confirmed by a second LVEF assessment within approximately 3 weeks also showing a documented drop. | Not Posted | Feb 2027 | From baseline until study completion (up to 5.5 years) | Participants |
From baseline until the primary completion date (up to approximately 1 year, 10 months)
Adverse events (AEs) were analyzed for the safety analysis population, which included all participants who received at least one dose of study medication, according to the treatment actually received. One participant randomized to Arm A (IV) mistakenly received 1 SC injection of pertuzumab and trastuzumab FDC SC and was counted in Arm B (SC) for safety; total number analyzed in Arm A: 101-1=100, Arm B: 99+1=100. AEs are still being collected and will be updated within 1 year of study completion.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | Participants received 8 cycles of neoadjuvant chemotherapy: 4 cycles of doxorubicin plus cyclophosphamide (AC) once every 3 weeks (Q3W) followed by docetaxel Q3W for 4 cycles. Pertuzumab and trastuzumab were given intravenously (IV) for 4 cycles Q3W concurrently with the taxane component of chemotherapy. After completing their neoadjuvant therapy, participants underwent surgery. Thereafter, participants received an additional 14 cycles of pertuzumab IV and trastuzumab IV for a total of 18 cycles. | 0 | 100 | 19 | 100 | 96 | 100 |
| EG001 | Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Participants received 8 cycles of neoadjuvant chemotherapy: 4 cycles of AC Q3W followed by docetaxel Q3W for 4 cycles. The pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) were given subcutaneously (SC) for 4 cycles (Q3W) concurrently with the taxane component of chemotherapy. After completing their neoadjuvant therapy, participants underwent surgery. Thereafter, participants received an additional 14 cycles of the PH FDC SC for a total of 18 cycles. | 1 | 100 | 18 | 100 | 98 | 100 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| ANAEMIA | Blood and lymphatic system disorders | MedDRA v24.1 | Systematic Assessment |
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| FEBRILE NEUTROPENIA | Blood and lymphatic system disorders | MedDRA v24.1 | Systematic Assessment |
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| MYELOSUPPRESSION | Blood and lymphatic system disorders | MedDRA v24.1 | Systematic Assessment |
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| CARDIAC FAILURE | Cardiac disorders | MedDRA v24.1 | Systematic Assessment |
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| MYOCARDIAL INFARCTION | Cardiac disorders | MedDRA v24.1 | Systematic Assessment |
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| ILEUS | Gastrointestinal disorders | MedDRA v24.1 | Systematic Assessment |
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| SUDDEN CARDIAC DEATH | General disorders | MedDRA v24.1 | Systematic Assessment |
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| DRUG-INDUCED LIVER INJURY | Hepatobiliary disorders | MedDRA v24.1 | Systematic Assessment |
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| HEPATIC FUNCTION ABNORMAL | Hepatobiliary disorders | MedDRA v24.1 | Systematic Assessment |
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| LIVER INJURY | Hepatobiliary disorders | MedDRA v24.1 | Systematic Assessment |
| |
| GASTROENTERITIS | Infections and infestations | MedDRA v24.1 | Systematic Assessment |
| |
| PNEUMONIA | Infections and infestations | MedDRA v24.1 | Systematic Assessment |
| |
| POSTOPERATIVE WOUND INFECTION | Infections and infestations | MedDRA v24.1 | Systematic Assessment |
| |
| UPPER RESPIRATORY TRACT INFECTION | Infections and infestations | MedDRA v24.1 | Systematic Assessment |
| |
| RADIATION SKIN INJURY | Injury, poisoning and procedural complications | MedDRA v24.1 | Systematic Assessment |
| |
| SKIN FLAP NECROSIS | Injury, poisoning and procedural complications | MedDRA v24.1 | Systematic Assessment |
| |
| ALANINE AMINOTRANSFERASE INCREASED | Investigations | MedDRA v24.1 | Systematic Assessment |
| |
| ASPARTATE AMINOTRANSFERASE INCREASED | Investigations | MedDRA v24.1 | Systematic Assessment |
| |
| EJECTION FRACTION DECREASED | Investigations | MedDRA v24.1 | Systematic Assessment |
| |
| GAMMA-GLUTAMYLTRANSFERASE INCREASED | Investigations | MedDRA v24.1 | Systematic Assessment |
| |
| NEUTROPHIL COUNT DECREASED | Investigations | MedDRA v24.1 | Systematic Assessment |
| |
| PLATELET COUNT DECREASED | Investigations | MedDRA v24.1 | Systematic Assessment |
| |
| WHITE BLOOD CELL COUNT DECREASED | Investigations | MedDRA v24.1 | Systematic Assessment |
| |
| HYPERGLYCAEMIA | Metabolism and nutrition disorders | MedDRA v24.1 | Systematic Assessment |
| |
| HYPOALBUMINAEMIA | Metabolism and nutrition disorders | MedDRA v24.1 | Systematic Assessment |
| |
| FIBROADENOMA OF BREAST | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA v24.1 | Systematic Assessment |
| |
| UTERINE LEIOMYOMA | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA v24.1 | Systematic Assessment |
| |
| ANXIETY | Psychiatric disorders | MedDRA v24.1 | Systematic Assessment |
| |
| BREAST PAIN | Reproductive system and breast disorders | MedDRA v24.1 | Systematic Assessment |
| |
| CHYLOTHORAX | Respiratory, thoracic and mediastinal disorders | MedDRA v24.1 | Systematic Assessment |
| |
| INTERSTITIAL LUNG DISEASE | Respiratory, thoracic and mediastinal disorders | MedDRA v24.1 | Systematic Assessment |
| |
| RASH | Skin and subcutaneous tissue disorders | MedDRA v24.1 | Systematic Assessment |
| |
| EMBOLISM | Vascular disorders | MedDRA v24.1 | Systematic Assessment |
| |
| HYPERTENSION | Vascular disorders | MedDRA v24.1 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| ANAEMIA | Blood and lymphatic system disorders | MedDRA v24.1 | Systematic Assessment |
| |
| FEBRILE NEUTROPENIA | Blood and lymphatic system disorders | MedDRA v24.1 | Systematic Assessment |
| |
| LEUKOPENIA | Blood and lymphatic system disorders | MedDRA v24.1 | Systematic Assessment |
| |
| NEUTROPENIA | Blood and lymphatic system disorders | MedDRA v24.1 | Systematic Assessment |
| |
| ABDOMINAL PAIN UPPER | Gastrointestinal disorders | MedDRA v24.1 | Systematic Assessment |
| |
| CONSTIPATION | Gastrointestinal disorders | MedDRA v24.1 | Systematic Assessment |
| |
| DIARRHOEA | Gastrointestinal disorders | MedDRA v24.1 | Systematic Assessment |
| |
| MOUTH ULCERATION | Gastrointestinal disorders | MedDRA v24.1 | Systematic Assessment |
| |
| NAUSEA | Gastrointestinal disorders | MedDRA v24.1 | Systematic Assessment |
| |
| STOMATITIS | Gastrointestinal disorders | MedDRA v24.1 | Systematic Assessment |
| |
| TOOTHACHE | Gastrointestinal disorders | MedDRA v24.1 | Systematic Assessment |
| |
| VOMITING | Gastrointestinal disorders | MedDRA v24.1 | Systematic Assessment |
| |
| INFLUENZA LIKE ILLNESS | General disorders | MedDRA v24.1 | Systematic Assessment |
| |
| MALAISE | General disorders | MedDRA v24.1 | Systematic Assessment |
| |
| PYREXIA | General disorders | MedDRA v24.1 | Systematic Assessment |
| |
| UPPER RESPIRATORY TRACT INFECTION | Infections and infestations | MedDRA v24.1 | Systematic Assessment |
| |
| URINARY TRACT INFECTION | Infections and infestations | MedDRA v24.1 | Systematic Assessment |
| |
| INFUSION RELATED REACTION | Injury, poisoning and procedural complications | MedDRA v24.1 | Systematic Assessment |
| |
| ALANINE AMINOTRANSFERASE INCREASED | Investigations | MedDRA v24.1 | Systematic Assessment |
| |
| ALPHA HYDROXYBUTYRATE DEHYDROGENASE INCREASED | Investigations | MedDRA v24.1 | Systematic Assessment |
| |
| ASPARTATE AMINOTRANSFERASE INCREASED | Investigations | MedDRA v24.1 | Systematic Assessment |
| |
| BLOOD ALKALINE PHOSPHATASE INCREASED | Investigations | MedDRA v24.1 | Systematic Assessment |
| |
| BLOOD CHOLESTEROL INCREASED | Investigations | MedDRA v24.1 | Systematic Assessment |
| |
| BLOOD CREATININE INCREASED | Investigations | MedDRA v24.1 | Systematic Assessment |
| |
| BLOOD LACTATE DEHYDROGENASE INCREASED | Investigations | MedDRA v24.1 | Systematic Assessment |
| |
| GAMMA-GLUTAMYLTRANSFERASE INCREASED | Investigations | MedDRA v24.1 | Systematic Assessment |
| |
| LYMPHOCYTE COUNT DECREASED | Investigations | MedDRA v24.1 | Systematic Assessment |
| |
| NEUTROPHIL COUNT DECREASED | Investigations | MedDRA v24.1 | Systematic Assessment |
| |
| PLATELET COUNT DECREASED | Investigations | MedDRA v24.1 | Systematic Assessment |
| |
| WEIGHT DECREASED | Investigations | MedDRA v24.1 | Systematic Assessment |
| |
| WHITE BLOOD CELL COUNT DECREASED | Investigations | MedDRA v24.1 | Systematic Assessment |
| |
| DECREASED APPETITE | Metabolism and nutrition disorders | MedDRA v24.1 | Systematic Assessment |
| |
| HYPERCHOLESTEROLAEMIA | Metabolism and nutrition disorders | MedDRA v24.1 | Systematic Assessment |
| |
| HYPERGLYCAEMIA | Metabolism and nutrition disorders | MedDRA v24.1 | Systematic Assessment |
| |
| HYPERTRIGLYCERIDAEMIA | Metabolism and nutrition disorders | MedDRA v24.1 | Systematic Assessment |
| |
| HYPERURICAEMIA | Metabolism and nutrition disorders | MedDRA v24.1 | Systematic Assessment |
| |
| HYPOALBUMINAEMIA | Metabolism and nutrition disorders | MedDRA v24.1 | Systematic Assessment |
| |
| HYPOKALAEMIA | Metabolism and nutrition disorders | MedDRA v24.1 | Systematic Assessment |
| |
| ARTHRALGIA | Musculoskeletal and connective tissue disorders | MedDRA v24.1 | Systematic Assessment |
| |
| MYALGIA | Musculoskeletal and connective tissue disorders | MedDRA v24.1 | Systematic Assessment |
| |
| PAIN IN EXTREMITY | Musculoskeletal and connective tissue disorders | MedDRA v24.1 | Systematic Assessment |
| |
| DIZZINESS | Nervous system disorders | MedDRA v24.1 | Systematic Assessment |
| |
| HEADACHE | Nervous system disorders | MedDRA v24.1 | Systematic Assessment |
| |
| HYPOAESTHESIA | Nervous system disorders | MedDRA v24.1 | Systematic Assessment |
| |
| INSOMNIA | Psychiatric disorders | MedDRA v24.1 | Systematic Assessment |
| |
| COUGH | Respiratory, thoracic and mediastinal disorders | MedDRA v24.1 | Systematic Assessment |
| |
| ALOPECIA | Skin and subcutaneous tissue disorders | MedDRA v24.1 | Systematic Assessment |
| |
| RASH | Skin and subcutaneous tissue disorders | MedDRA v24.1 | Systematic Assessment |
| |
| HYPERTENSION | Vascular disorders | MedDRA v24.1 | Systematic Assessment |
|
The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Communications | Hoffmann-La Roche | 800-821-8590 | genentech@druginfo.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jun 3, 2021 | Dec 6, 2022 | SAP_001.pdf |
Not provided
| ID | Term |
|---|---|
| C485206 | pertuzumab |
| D000068878 | Trastuzumab |
| D004317 | Doxorubicin |
| D003520 | Cyclophosphamide |
| D000077143 | Docetaxel |
| D013514 | Surgical Procedures, Operative |
| ID | Term |
|---|---|
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| D003630 | Daunorubicin |
| D018943 | Anthracyclines |
| D009279 | Naphthacenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D011083 | Polycyclic Compounds |
| D000617 | Aminoglycosides |
| D006027 | Glycosides |
| D002241 | Carbohydrates |
| D010752 | Phosphoramide Mustards |
| D009588 | Nitrogen Mustard Compounds |
| D009150 | Mustard Compounds |
| D006846 | Hydrocarbons, Halogenated |
| D063088 | Phosphoramides |
| D009943 | Organophosphorus Compounds |
| D043823 | Taxoids |
| D043822 | Cyclodecanes |
| D003516 | Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
| D004224 | Diterpenes |
| D013729 | Terpenes |
Not provided
Not provided
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| ER Positive and PgR Positive |
|
| Stage IIIB-IIIC |
|
| OG001 | Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Participants received 8 cycles of neoadjuvant chemotherapy: 4 cycles of AC Q3W followed by docetaxel Q3W for 4 cycles. The pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) were given subcutaneously (SC) for 4 cycles (Q3W) concurrently with the taxane component of chemotherapy. After completing their neoadjuvant therapy, participants underwent surgery. Thereafter, participants received an additional 14 cycles of the PH FDC SC for a total of 18 cycles. |
|
|
|
| OG001 | Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | Participants received 8 cycles of neoadjuvant chemotherapy: 4 cycles of AC Q3W followed by docetaxel Q3W for 4 cycles. The pertuzumab and trastuzumab fixed-dose combination for subcutaneous administration (PH FDC SC) were given subcutaneously (SC) for 4 cycles (Q3W) concurrently with the taxane component of chemotherapy. After completing their neoadjuvant therapy, participants underwent surgery. Thereafter, participants received an additional 14 cycles of the PH FDC SC for a total of 18 cycles. |
|
|
|