A Two-Arm Study to Evaluate the Pharmacokinetics, Efficacy, and Safety of Subcutaneous Administration of the Fixed-Dose Combination of Pertuzumab and Trastuzumab in Combination With Chemotherapy in Chinese Participants With HER2-Positive Early Breast Cancer

NCT04024462 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: YO41137
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 18

Brief Summary

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.

Conditions

HER2-positive Early Breast Cancer

Outcome Measures

Primary Outcomes (2)

• 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)

Secondary Outcomes (10)

• Percentage of Participants With Total Pathological Complete Response (tpCR), According to Local Pathologist Assessment

  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

  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

  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

  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

  From baseline to EFS (including SPNBC) event (up to 5.5 years)

Study Arms (2)

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.

Drug: Pertuzumab IV; Drug: Trastuzumab IV; Drug: Doxorubicin; Drug: Cyclophosphamide; Drug: Docetaxel; Procedure: Surgery; Radiation: Post-Operative Radiotherapy; Drug: Hormone Therapy

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.

Drug: Pertuzumab and Trastuzumab FDC SC; Drug: Doxorubicin; Drug: Cyclophosphamide; Drug: Docetaxel; Procedure: Surgery; Radiation: Post-Operative Radiotherapy; Drug: Hormone Therapy

Interventions

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.

Also known as: Perjeta, RO4368451

Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy

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.

Also known as: Herceptin, RO0452317

Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy

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.

Also known as: Pertuzumab, Trastuzumab, and Hyaluronidase-zzxf, PHESGO™, PH FDC SC, RG6264, RO7198574

Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy

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.

Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy; Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy

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.

Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy; Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy

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.

Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy; Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy

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.

Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy; Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy

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).

Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy; Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy

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.

Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy; Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ability to comply with the study protocol, in the investigator's judgment
• Eastern Cooperative Oncology Group (ECOG) Performance Status greater or equal to (≤)1
• Stage II-IIIC (T2-T4 plus any N, or any T plus N1-3, M0), locally advanced, inflammatory, or early-stage, unilateral, and histologically confirmed invasive breast cancer
• Primary tumor greater than (\>)2 centimeters (cm) in diameter, or node-positive disease (clinically or on imaging, and node positivity confirmed with cytology and/or histopathology)
• Human Epidermal Growth Factor Receptor 2 (HER2)-positive breast cancer confirmed by a central laboratory prior to study enrollment. HER2-positive status will be determined based on pretreatment breast biopsy material and defined as 3+ by immunohistochemistry (IHC) and/or positive by HER2 amplification by in situ hybridization (ISH) with a ratio of ≥2 for the number of HER2 gene copies to the number of signals for chromosome 17 copies
• Hormone receptor status of the primary tumor, centrally confirmed
• Patient agreement to undergo mastectomy or breast conserving surgery after neoadjuvant therapy
• Availability of formalin-fixed, paraffin-embedded (FFPE) tumor tissue for central confirmation of HER2, hormone receptor status, and PIK3CA mutational analyses
• Baseline left ventricular ejection fraction (LVEF) ≥55% measured by echocardiogram (ECHO) or multiple-gated acquisition scan (MUGA)
• For women of childbearing potential (WOCBP) who are sexually active: agreement to remain abstinent (refrain from heterosexual intercourse) or use one highly effective non-hormonal contraceptive method with a failure rate of less than (\<)1% per year, or two effective non-hormonal contraceptive methods during the treatment period and for 7 months after the last dose of HER2-targeted therapy, and agreement to refrain from donating eggs during this same period
• For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom in combination with a spermicidal foam, gel, film, cream, or suppository, and agreement to refrain from donating sperm, as specified in the protocol
• A negative serum pregnancy test must be available prior to randomization for WOCBP (premenopausal women and women \<12 months after the onset of menopause), unless they have undergone surgical sterilization (removal of ovaries and/or uterus)
• No major surgical procedure unrelated to breast cancer within 28 days prior to randomization or anticipation of the need for major surgery during the course of study treatment

You may not qualify if:

• Stage IV (metastatic) breast cancer
• History of invasive breast cancer
• History of concurrent or previously treated non-breast malignancies except for appropriately treated 1) non-melanoma skin cancer and/or 2) in situ carcinomas, including cervix, colon, and skin
• Have received any previous systemic therapy (including chemotherapy, immunotherapy, HER2-targeted agents, endocrine therapy \[selective estrogen receptor modulators, aromatase inhibitors\], and antitumor vaccines) for treatment or prevention of breast cancer, or radiation therapy for treatment of cancer
• Have a past history of ductal carcinoma in situ (DCIS) or lobular carcinoma in situ (LCIS) if they have received any systemic therapy for its treatment or radiation therapy to the ipsilateral breast
• High-risk for breast cancer and have received chemopreventative drugs in the past
• Multicentric (multiple tumors involving more than one quadrant) breast cancer, unless all tumors are HER2-positive
• Bilateral breast cancer
• Have undergone an excisional biopsy of primary tumor and/or axillary lymph nodes
• Axillary lymph node dissection (ALND) prior to initiation of neoadjuvant therapy
• Sentinel lymph node biopsy (SLNB) prior to neoadjuvant therapy
• Treatment with any investigational drug within 28 days prior to randomization
• Serious cardiac illness or medical conditions
• Inadequate bone marrow function
• Impaired liver function

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (18)

Peking University People's Hospital

Beijing, 100044, China

Location

Beijing Cancer Hospital

Beijing, 100142, China

Location

Jilin Cancer Hospital

Changchun, 130012, China

Location

The First Hospital of Jilin University

Changchun, 130021, China

Location

West China Hospital, Sichuan University

Chengdu, 610041, China

Location

The 900th Hospital of PLA joint service support force

Fuzhou, 110016, China

Location

Sun Yet-sen University Cancer Center

Guangzhou, 510060, China

Location

Zhejiang Cancer Hospital

Hangzhou, 310022, China

Location

Harbin Medical University Cancer Hospital

Harbin, 150081, China

Location

Shandong Cancer Hospital

Jinan, 250117, China

Location

Jiangsu Province Hospital

Nanjing, 210036, China

Location

The Affiliated Hospital of Medical College Qingdao University

Qingdao, 266003, China

Location

Ruijin Hospital, Shanghai Jiaotong University School of Medicine

Shanghai, 200025, China

Location

Fudan University Shanghai Cancer Center

Shanghai, 200032, China

Location

Hebei Medical University Fourth Hospital

Shijiazhuang, 050035, China

Location

Union Hospital Tongji Medical College Huazhong University of Science and Technology

Wuhan, 430023, China

Location

Hubei Cancer Hospital

Wuhan, 430079, China

Location

The First Affiliated Hospital of Xian Jiao Tong University

Xi'an, 710061, China

Location

MeSH Terms

Interventions

pertuzumab; Trastuzumab; Doxorubicin; Cyclophosphamide; Docetaxel; Surgical Procedures, Operative

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Diterpenes; Terpenes

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800-821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 17, 2019
• First Posted: July 18, 2019
• Study Start: February 5, 2020
• Primary Completion: December 13, 2021
• Study Completion: January 19, 2026
• Last Updated: February 20, 2026
• Results First Posted: February 16, 2023

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share

Locations

CN (18)