A Study to Evaluate Patient Preference for Home Administration of Fixed-Dose Combination of Pertuzumab and Trastuzumab for Subcutaneous Administration in Participants With Early or Locally Advanced/Inflammatory HER2-Positive Breast Cancer

NCT05415215 | Completed Phase 3 Results FDA Drug

• 3 other identifiers: MO431102021-002346-332023-506380-33-00
• Study Type: interventional
• Target: 346
• Locations: 17 countries
• Sites: 45

Brief Summary

This is a Phase IIIb, multinational, multicenter, randomized, open-label study to evaluate patient preference of the fixed-dose combination of pertuzumab and trastuzumab for subcutaneous use (PH FDC SC) administration in the home setting compared with the hospital setting during the cross-over period of adjuvant treatment in participants with early or locally advanced/inflammatory human epidermal growth factor receptor 2-positive (HER2+) breast cancer.

Conditions

Inflammatory Breast Cancer; Locally Advanced Breast Cancer; Early Breast Cancer

Keywords

patient preference; home administration; fixed-dose combination of pertuzumab and trastuzumab; subcutaneous administration

Outcome Measures

Primary Outcomes (1)

• Cross-over Period: Percentage of Participants Who Preferred the Administration of PH FDC SC in the Home Setting Compared With the Hospital Setting in Question 1 of the Patient Preference Questionnaire (PPQ)

  The PPQ was used to evaluate the participant preference for PH FDC SC compared to P+H IV. Participants completed the PPQ, where Question (Q) 1 was: "All things considered, which setting for your treatment did you prefer?" Participants were required to select one of the following options: home, hospital or no preference. The reported results show the percentage of participants who preferred receiving PH FDC SC at home setting over the hospital setting. Percentages were rounded off.

  Upon completion of adjuvant cross-over period (Day 1 of Cycle 8 or 9; Cycle length = 21 days)

Secondary Outcomes (27)

• Neoadjuvant Phase: Percentage of HCPs by Their Responses to Question 1a of HCPQ - Drug Preparation Area

  Day 1 of Cycles 1-8 (Cycle length = 21 days)

• Neoadjuvant Phase: Duration of Treatment Preparation, According to Healthcare Professionals' Responses to Question 1b of HCPQ - Drug Preparation Area

  Day 1 of Cycles 1-8 (Cycle length = 21 days)

• Neoadjuvant Phase: Percentage of HCPs by Their Response to Question 2 of the HCPQ - Drug Preparation Area

  Up to Day 1 of Cycle 8 (Cycle length = 21 days)

• Neoadjuvant Phase: Percentage of HCPs by Their Responses to Questions 1a-1e of the HCPQ - Administering Treatment

  Day 1 of Cycles 1-8 (Cycle length = 21 days)

• Neoadjuvant Phase: Duration of Treatment Administration According to HCPs' Responses to Questions 1c (Sub-part), 1f, and 1g of the HCPQ - Administering Treatment

  Day 1 of Cycles 1-8 (Cycle length = 21 days)

Study Arms (5)

Arm A: Pertuzumab IV and Trastuzumab IV Plus Investigator's Choice of Chemotherapy

OTHER

During the neoadjuvant phase, the enrolled participants randomized to this arm will receive treatment with pertuzumab and trastuzumab intravenously (PH IV) plus investigator's choice of chemotherapy (Option 1, 2, or 3). With chemotherapy Option 1, PH IV will be administered at each cycle from Cycles 1 to 6 (1 cycle is 3 weeks); with chemotherapy Options 2 and 3, PH IV will be administered once per cycle from Cycles 5 to 8 (1 cycle is 3 weeks).

Drug: Pertuzumab IV; Drug: Trastuzumab IV; Drug: Investigator's Choice of Chemotherapy; Procedure: Surgery; Radiation: Radiotherapy

Arm B: PH FDC SC Plus Investigator's Choice of Chemotherapy

OTHER

During the neoadjuvant phase, the enrolled participants randomized to this arm will receive treatment with the fixed dose combination of pertuzumab and trastuzumab for subcutaneous use (PH FDC SC) plus investigator's choice of chemotherapy (Option 1, 2, or 3). With chemotherapy Option 1, PH FDC SC will be administered at each cycle from Cycles 1 to 6 (1 cycle is 3 weeks); with chemotherapy Options 2 and 3, PH FDC SC will be administered once per cycle from Cycles 5 to 8 (1 cycle is 3 weeks).

Drug: Fixed Dose Combination of Pertuzumab and Trastuzumab for Subcutaneous Use (PH FDC SC); Drug: Investigator's Choice of Chemotherapy; Procedure: Surgery; Radiation: Radiotherapy

Arm C: Adjuvant PH FDC SC in Hospital, Then at Home

EXPERIMENTAL

During the adjuvant phase, participants who have achieved pCR after surgery will be treated with 2 cycles of PH FDC SC in the hospital (run-in period). After completion of the last cycle of radiotherapy and the last cycle of PH FDC SC (run-in period), participants will then be randomized with a ratio of 1:1 into one of two treatment arms (Arm C or D) in a cross-over treatment period to receive the next 6 cycles of PH FDC SC treatment. Participants in Arm C will receive 3 cycles of PH FDC SC in the hospital and then 3 cycles of PH FDC SC in the home setting. After the cross-over treatment period, participants will receive the remaining PH FDC SC treatment cycles required to complete the planned 18 cycles of HER2-directed therapy, unless of disease recurrence, unacceptable toxicity, or withdrawal. Study treatment during this treatment continuation period will be administered either in the hospital or in the home setting as selected by the participant at the end of the crossover period.

Drug: Fixed Dose Combination of Pertuzumab and Trastuzumab for Subcutaneous Use (PH FDC SC)

Arm D: Adjuvant PH FDC SC at Home, Then in Hospital

EXPERIMENTAL

During the adjuvant phase, participants who have achieved pCR after surgery will be treated with 2 cycles of PH FDC SC in the hospital (run-in period). After completion of the last cycle of radiotherapy and the last cycle of PH FDC SC (run-in period), participants will then be randomized with a ratio of 1:1 into one of two treatment arms (Arm C or D) in a cross-over treatment period to receive the next 6 cycles of PH FDC SC treatment. Participants in Arm D will receive 3 cycles of PH FDC SC in the home setting and then 3 cycles of PH FDC SC in the hospital. After the cross-over treatment period, participants will receive the remaining PH FDC SC treatment cycles required to complete the planned 18 cycles of HER2-directed therapy, unless of disease recurrence, unacceptable toxicity, or withdrawal. Study treatment during this treatment continuation period will be administered either in the hospital or in the home setting as selected by the participant at the end of the crossover period.

Drug: Fixed Dose Combination of Pertuzumab and Trastuzumab for Subcutaneous Use (PH FDC SC)

Arm E: Adjuvant Trastuzumab Emtansine

OTHER

Participants with pathological evidence of residual invasive carcinoma in the breast or axillary lymph nodes following completion of preoperative therapy and surgery will enter Arm E to receive trastuzumab emtansine for 14 cycles. Trastuzumab emtansine will be administered IV in the hospital as per prescribing information.

Drug: Trastuzumab Emtansine

Interventions

Fixed Dose Combination of Pertuzumab and Trastuzumab for Subcutaneous Use (PH FDC SC) DRUG

PH FDC SC is administered subcutaneously (SC) as a fixed non-weight-based dose. A loading dose of 1200 milligram (mg) pertuzumab, 600 mg trastuzumab, and 30,000 units of recombinant human PH20 hyaluronidase (rHuPH20) is given in the first cycle (1 cycle is 21 days). In subsequent cycles, maintenance doses of 600 mg pertuzumab, 600 mg trastuzumab, and 20,000 units rHuPH20 are administered once every 3 weeks (Q3W).

Also known as: PHESGO®, Pertuzumab, Trastuzumab, and Hyaluronidase-zzxf, Pertuzumab, Trastuzumab, and rHuPH20, RO7198574, RG6264

Arm B: PH FDC SC Plus Investigator's Choice of Chemotherapy; Arm C: Adjuvant PH FDC SC in Hospital, Then at Home; Arm D: Adjuvant PH FDC SC at Home, Then in Hospital

Trastuzumab IV DRUG

Trastuzumab is given as an 8 milligram per kilogram (mg/kg) intravenous (IV) loading dose and then 6 mg/kg IV for subsequent maintenance doses once every 3 weeks.

Also known as: Herceptin®, RO0452317

Arm A: Pertuzumab IV and Trastuzumab IV Plus Investigator's Choice of Chemotherapy

Trastuzumab Emtansine DRUG

Trastuzumab emtansine will be given at a dose of 3.6 mg/kg by intravenous (IV) infusion, once every 3 weeks.

Also known as: Kadcyla®, ado-trastuzumab emtansine, T-DM1, RO5304020

Arm E: Adjuvant Trastuzumab Emtansine

Investigator's Choice of Chemotherapy DRUG

Option 1: Docetaxel and carboplatin once every 3 weeks for 6 cycles; Option 2: Doxorubicin plus cyclophosphamide once every 3 weeks for 4 cycles, followed by a taxane (docetaxel once every 3 weeks for 4 cycles or paclitaxel once every week for 12 cycles); Option 3: Dose-dense doxorubicin plus cyclophosphamide (ddAC) once every 2 weeks for 4 cycles, followed by a taxane (docetaxel once every 3 weeks for 4 cycles or paclitaxel once every week for 12 cycles).

Arm A: Pertuzumab IV and Trastuzumab IV Plus Investigator's Choice of Chemotherapy; Arm B: PH FDC SC Plus Investigator's Choice of Chemotherapy

Radiotherapy RADIATION

After surgery, radiotherapy is to be given as clinically indicated and as per local practice or institutional standards. The selected radiotherapy regimen should be initiated within 4 weeks after surgery.

Arm A: Pertuzumab IV and Trastuzumab IV Plus Investigator's Choice of Chemotherapy; Arm B: PH FDC SC Plus Investigator's Choice of Chemotherapy

Pertuzumab IV DRUG

Pertuzumab is given as a fixed dose of 840 mg intravenous (IV) loading dose and then 420 mg IV for subsequent maintenance doses once every 3 weeks.

Also known as: Perjeta®, RO4368451

Arm A: Pertuzumab IV and Trastuzumab IV Plus Investigator's Choice of Chemotherapy

Surgery PROCEDURE

After completing their neoadjuvant therapy, participants will undergo surgical resection for early or locally advanced HER2+ breast cancer (if eligible for surgery). Participants may undergo breast-conserving surgery or mastectomy according to routine clinical practice. The surgery cannot be performed ≤2 weeks from the last systemic neoadjuvant therapy and must be performed ≤6 weeks after the last systemic neoadjuvant therapy.

Arm A: Pertuzumab IV and Trastuzumab IV Plus Investigator's Choice of Chemotherapy; Arm B: PH FDC SC Plus Investigator's Choice of Chemotherapy

Eligibility Criteria

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

You may qualify if:

• Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• Intact skin at planned site of subcutaneous (SC) injections
• Left ventricular ejection fraction (LVEF) greater than or equal to (≥)55% by echocardiogram (ECHO) or multiple-gated acquisition scan (MUGA)
• Negative human immunodeficiency virus (HIV) test at screening
• Negative hepatitis B surface antigen (HBsAg) test at screening
• Positive hepatitis B surface antibody (HBsAb) test at screening, or negative HBsAb at screening accompanied by either of the following: Negative total hepatitis B core antibody (HBcAb); Positive total HBcAb test followed by a negative (per local laboratory definition) hepatitis B virus (HBV) DNA test
• Negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody test followed by a negative HCV RNA test at screening
• For female participants of childbearing potential: agreement to remain abstinent or use contraception and agree to refrain from donating eggs during the treatment period and for 7 months after the final dose of the study treatment
• For male participants: agreement to remain abstinent or use a condom, and agree to refrain from donating sperm during the treatment period and for 7 months after the final dose of study treatment
• Female and male participants with stage II-IIIC early or locally advanced/inflammatory human epidermal growth factor receptor 2-positive (HER2+) breast cancer
• Primary tumor \>2 centimetres (cm) in diameter, or node-positive disease
• HER2+ breast cancer confirmed by a local laboratory prior to study enrollment. HER2+ 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) following American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines 2018 and updates (Wolff et al. Arch Pathol Lab Med 2018)
• Hormone receptor status of the primary tumor determined by local assessment following American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines and updates (Allison et al. J Clin Oncol 2020)
• Agreement to undergo mastectomy or breast conserving surgery after neoadjuvant therapy, including the axillary nodes
• Availability of formalin-fixed, paraffin-embedded (FFPE) tumor tissue block for local confirmation of HER2 and hormone receptor status following current ASCO/CAP guidelines

You may not qualify if:

• Stage IV (metastatic) 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. A participant with previous invasive non-breast cancer is eligible provided he/she has been disease free for more than 5 years
• Participants who are pregnant or breastfeeding or intending to become pregnant during the study or within 7 months after the final dose of study treatments
• Treatment with investigational therapy within 28 days prior to initiation of study treatment
• Active, unresolved infections at screening requiring treatment
• Participants who may have had a recent episode of thromboembolism and are still trying to optimize the anticoagulation dose and/or have not normalized their International Normalized Ratio (INR)
• Serious cardiac illness or medical conditions
• History of ventricular dysrhythmias or risk factors for ventricular dysrhythmias
• Inadequate bone marrow function
• Impaired liver function
• Renal function with creatinine clearance \<50 mL/min using the Cockroft-Gault formula and serum creatinine \>1.5x upper limit of normal (ULN)
• Major surgical procedure unrelated to breast cancer within 28 days prior to study entry or anticipation of the need for major surgery during the course of study treatment
• Current severe, uncontrolled systemic disease that may interfere with planned treatment
• Any serious medical condition or abnormality in clinical laboratory tests that precludes an individual's safe participation in and completion of the study
• Treatment with a live vaccine (e.g., FluMist) in the 30 days prior to initiation of study treatment, or anticipation of need for such a vaccine during treatment or within 90 days after the final dose of study treatment

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (45)

Centro de Investigaciones Médicas y Desarrollo LC S.R.L

Buenos Aires, Ciudad Autónoma de BuenosAires, C1113AAE, Argentina

Location

Centro Oncologico Korben

Ciudad Autonoma Buenos Aires, C1426AGE, Argentina

Location

University Clinical Center of the Republic of Srpska

Banja Luka, 78000, Bosnia and Herzegovina

Location

Cantonal Hospital Zenica

Zenica, 72000, Bosnia and Herzegovina

Location

Crio - Centro Regional Integrado de Oncologia

Fortaleza, Ceará, 60336-550, Brazil

Location

Hospital Araujo Jorge

Goiânia, Goiás, 74605-070, Brazil

Location

Hospital Nossa Senhora da Conceicao

Porto Alegre, Rio Grande do Sul, 91350-200, Brazil

Location

Clinica de Pesquisa e Centro de Estudos em Oncologia Ginecologica e Mamaria Ltda

São Paulo, São Paulo, 01317-001, Brazil

Location

Multiprofile Hospital for Active Treatment Uni Hospital

Panagyurishte, 4500, Bulgaria

Location

Complex Oncology Center - Plovdiv First Internal Chemotherapy Department

Plovdiv, 4004, Bulgaria

Location

MHAT Nadezhda

Sofia, 1330, Bulgaria

Location

Royal Victoria Regional Health Centre

Barrie, Ontario, L4M 6M2, Canada

Location

Lakeridge Health Oshawa

Oshawa, Ontario, L1G 2B9, Canada

Location

North York General Hospital

Toronto, Ontario, M2K 1E1, Canada

Location

Jewish General Hospital

Montreal, Quebec, H3T 1E2, Canada

Location

Hopital du Saint Sacrement

Québec, Quebec, G1S 4L8, Canada

Location

Clinica Vespucio

Santiago, 8241479, Chile

Location

Centro de Estudios Clínicos SAGA

Santiago, Chile

Location

Clinica CIMCA

San José, 10103, Costa Rica

Location

ICIMED Instituto de Investigación en Ciencias Médicas

San José, 10108, Costa Rica

Location

Hospital Metropolitano (Sede Lindora-Santa Ana)

San José, 10903, Costa Rica

Location

Clinical Hospital Centre Zagreb

Zagreb, 10000, Croatia

Location

Saifee Hospital

Mumbai, Maharashtra, 400004, India

Location

TATA Medical Centre

Kolkata, West Bengal, 700156, India

Location

International Cancer Institute (ICI)

Eldoret, 30100, Kenya

Location

The Aga Khan University-Kenya.

Nairobi, 00100, Kenya

Location

Iem-Fucam

D.F., Mexico City, 04980, Mexico

Location

Health Pharma Professional Research

Mexico City, Mexico City, 03100, Mexico

Location

Oncologico Potosino

San Luis Potosí City, San Luis Potosí, 78209, Mexico

Location

Instituto Regional de Enfermedades Neoplásicas del Sur

Arequipa, 5154, Peru

Location

Oncocenter Peru S.A.C.

Lima, Lima 41, Peru

Location

National Cancer Centre

Singapore, 168583, Singapore

Location

Tan Tock Seng Hospital

Singapore, 308433, Singapore

Location

Medical Oncology Centre of Rosebank

Johannesburg, 2196, South Africa

Location

Wilgers Oncology Centre

Pretoria, 0001, South Africa

Location

Korea University Anam Hospital

Seoul, 02841, South Korea

Location

Samsung Medical Center

Seoul, 06351, South Korea

Location

Complejo Hospitalario de Jaen-Hospital Universitario Medico Quirurgico

Jaén, 23007, Spain

Location

Hospital Universitario Virgen de Arrixaca

Murcia, 30120, Spain

Location

Hospital Clinico Universitario de Salamanca

Salamanca, 37007, Spain

Location

Gulhane Training and Research Hospital

Ankara, 06010, Turkey (Türkiye)

Location

Ankara City Hospital

Ankara, 06800, Turkey (Türkiye)

Location

Trakya University Medical Faculty Research And Practice Hospital Medical Oncology Department

Edirne, 22770, Turkey (Türkiye)

Location

Ba?c?lar Medipol Mega Üniversite Hastanesi

Istanbul, 34214, Turkey (Türkiye)

Location

Hacettepe Uni Medical Faculty Hospital

Sihhiye/Ankara, 06230, Turkey (Türkiye)

Location

MeSH Terms

Conditions

Breast Neoplasms; Inflammatory Breast Neoplasms; Patient Preference

Interventions

Trastuzumab; Injections, Subcutaneous; pertuzumab; Ado-Trastuzumab Emtansine; Surgical Procedures, Operative; Radiotherapy

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Patient Satisfaction; Treatment Adherence and Compliance; Health Behavior; Behavior

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Injections; Drug Administration Routes; Drug Therapy; Therapeutics; Maytansine; Macrolides; Lactones; Organic Chemicals; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds

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: June 8, 2022
• First Posted: June 13, 2022
• Study Start: July 5, 2022
• Primary Completion: November 20, 2024
• Study Completion: November 7, 2025
• Last Updated: February 10, 2026
• Results First Posted: January 12, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share

Locations

ME (3); BO (2); CL (2); CO (3); KR (2); PE (2); CA (5); BU (3); SG (2); TU (5); AR (2); KE (2); ZA (2); ES (3); CR (1); IN (2); BR (4)