A Study to Evaluate the Efficacy and Safety of Inavolisib in Combination With Phesgo Versus Placebo in Combination With Phesgo in Participants With PIK3CA-Mutated HER2-Positive Locally Advanced or Metastatic Breast Cancer

A Phase III, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Efficacy and Safety of Inavolisib in Combination With Phesgo Versus Placebo in Combination With Phesgo As Maintenance Therapy After First Line Induction Therapy in Participants With PIK3CA-Mutated HER2-Positive Locally Advanced or Metastatic Breast Cancer

This study will evaluate the efficacy and safety of inavolisib in combination with Phesgo (pertuzumab, trastuzumab, and rHuPH20 injection for subcutaneous use) compared with placebo in combination with Phesgo, as maintenance therapy, after induction therapy in participants with previously untreated HER2-positive advanced breast cancer (ABC).

Study Overview

• Status: Recruiting
• Conditions: Metastatic Breast Cancer
• Intervention / Treatment: Drug: Phesgo; Drug: Taxane-based Chemotherapy; Drug: Inavolisib; Drug: Optional Endocrine Therapy of Investigator's Choice; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 230
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Reference Study ID Number: WO44263 https://forpatients.roche.com/; Phone Number: 888-662-6728 (U.S. Only); Email: global-roche-genentech-trials@gene.com

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1125ABD
    • Recruiting
    • Fundacion CENIT para la investigacion en Neurociencias
  • Ciudad Autonoma Buenos Aires, Argentina, C1426AGE
    • Recruiting
    • Centro Oncologico Korben; Oncology
  • Rosario, Argentina, S2000KZE
    • Recruiting
    • Instituto de Oncologia de Rosario
  • Rosario, Argentina, S2002KDS
    • Recruiting
    • Hospital Provincial del Centenario
  • San Juan, Argentina, J5400DIL
    • Recruiting
    • CER San Juan Centro Polivalente de Asistencia e Investigacion Clinica
• Australia
  • New South Wales
    • Darlinghurst, New South Wales, Australia, 2010
      • Recruiting
      • Kinghorn Cancer Centre; St Vincents Hospital
    • Gosford, New South Wales, Australia, 2250
      • Recruiting
      • Gosford Hospital; Cancer Care Services
  • Queensland
    • Sippy Downs, Queensland, Australia, 4556
      • Recruiting
      • University of the Sunshine Coast
  • Western Australia
    • Perth, Western Australia, Australia, 6009
      • Recruiting
      • Sir Charles Gairdner Hospital; Medical Oncology
• Belgium
  • Bruxelles, Belgium, 1200
    • Recruiting
    • Cliniques Universitaires St-Luc
  • Charleroi, Belgium, 6000
    • Recruiting
    • GHdC Site Notre Dame
  • Hasselt, Belgium, 3500
    • Recruiting
    • Jessa Zkh (Campus Virga Jesse)
  • Namur, Belgium, 5000
    • Recruiting
    • Clinique Ste-Elisabeth
• Brazil
  • GO
    • Goiania, GO, Brazil, 74605-070
      • Recruiting
      • Hospital Araujo Jorge; Departamento de Ginecologia E Mama
  • PE
    • Recife, PE, Brazil, 50040-000
      • Recruiting
      • Hospital do Cancer de Pernambuco - HCP
  • PR
    • Londrina, PR, Brazil, 86015-520
      • Recruiting
      • Hospital do Cancer de Londrina
  • RO
    • Porto Velho, RO, Brazil, 76834-899
      • Recruiting
      • Hospital de Amor Amazônia
  • RS
    • Porto Alegre, RS, Brazil, 90610-000
      • Recruiting
      • Hospital Sao Lucas - PUCRS
    • Porto Alegre, RS, Brazil, 90020-090
      • Recruiting
      • Santa Casa de Misericordia de Porto Alegre
  • SP
    • Barretos, SP, Brazil, 14784-400
      • Recruiting
      • Hospital de Cancer de Barretos
    • Sao Paulo, SP, Brazil, 01246-000
      • Recruiting
      • Instituto do Cancer do Estado de Sao Paulo - ICESP
    • Sao Paulo, SP, Brazil, 01317-001
      • Recruiting
      • Clinica de Pesquisa e Centro de Estudos em Oncologia Ginecologica e Mamaria Ltda
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4C2
      • Recruiting
      • Tom Baker Cancer Centre; Dept of Pathology
  • New Brunswick
    • Moncton, New Brunswick, Canada, E1C 6Z8
      • Recruiting
      • The Moncton Hospital
  • Quebec
    • Montreal, Quebec, Canada, H3T 1E2
      • Recruiting
      • Jewish General Hospital
    • Montreal, Quebec, Canada, H4J 1C5
      • Recruiting
      • Hôpital du Sacré-Coeur de Montreal
    • Quebec City, Quebec, Canada, G1S 4L8
      • Recruiting
      • Hopital du Saint Sacrement
  • Saskatchewan
    • Regina, Saskatchewan, Canada, S4T 7T1
      • Recruiting
      • Allan Blair Cancer Center
• China
  • Baoding, China, 071000
    • Recruiting
    • Affiliated Hospital of Hebei University; Department of medical oncology
  • Beijing, China, 100142
    • Recruiting
    • Beijing Cancer Hospital
  • Changchun City, China, 130021
    • Recruiting
    • The First Hospital of Jilin University
  • Chengdu, China, 610072
    • Recruiting
    • Sichuan Provincial People's Hospital
  • Chengdu, China, 610041
    • Recruiting
    • Sichuan Provincial Cancer Hospital
  • Fuzhou, China, 350014
    • Recruiting
    • Fujian cancer hospital
  • Hangzhou City, China, 310022
    • Recruiting
    • Zhejiang Cancer Hospital; Breast Surgery
  • Hangzhou City, China, 310009
    • Withdrawn
    • The Second Affiliated Hospital of Zhejiang University School of Medicine
  • Harbin, China, 150049
    • Recruiting
    • Harbin Medical University Tumor Hospital; Department of Surgery; Pharmacy
  • Jinan, China, 250117
    • Recruiting
    • Shandong Cancer Hospital
  • Luoyang City, China, 471031
    • Recruiting
    • The First Affiliated Hospital to Henan University of Science and Technology
  • Nanchang, China, 330006
    • Recruiting
    • The Second Affiliated Hospital to Nanchang University
  • Nanning City, China, 530021
    • Recruiting
    • Guangxi Cancer Hospital of Guangxi Medical University
  • Shantou City, China, 515031
    • Active, not recruiting
    • Shantou Center Hospital
  • Tianjin, China, 300000
    • Recruiting
    • Tianjin Cancer Hospital; Department of Breast Oncology
  • Wuhan, China, 430079
    • Recruiting
    • Hubei Cancer Hospital
  • Wuhan City, China, 430023
    • Recruiting
    • Union Hospital Tongji Medical College Huazhong University of Science and Technology
• Colombia
  • Barranquilla, Colombia, 080020
    • Recruiting
    • Clinica de la Costa
  • Bogota, D.C., Colombia, 110131
    • Recruiting
    • Fundación CTIC - Centro de Tratamiento e Investigación sobre Cáncer Luis Carlos Sarmiento Angulo
  • Monteria, Colombia, 230002
    • Recruiting
    • Oncomedica S.A.
• Finland
  • Tampere, Finland, 33520
    • Recruiting
    • Tampere University Hospital; Dept of Oncology
  • Turku, Finland, 20520
    • Recruiting
    • Turku Uni Central Hospital; Oncology Clinics
• Germany
  • Amberg, Germany, 92224
    • Recruiting
    • Klinikum St. Marien; Frauenklinik
  • Düsseldorf, Germany, 40235
    • Recruiting
    • Gynonco Düsseldorf, MVZ Medical Center GmbH
  • Erfurt, Germany, 99084
    • Recruiting
    • Frauenarztpraxis Dr. Apel, Dr. Kolpin
  • Freiburg, Germany, 79110
    • Recruiting
    • Praxis für Interdisziplinäre Onkologie und Hämatologie GbR
  • Saarbruecken, Germany, 66113
    • Recruiting
    • Caritas Klinik St. Theresia -Frauenklinik Brustzentrum
  • Stralsund, Germany, 18439
    • Recruiting
    • Gynäkologie Kompetenzzentrum; Praxis Dr. med. Carsten Hielscher
• Hong Kong
  • Hong Kong, Hong Kong
    • Recruiting
    • Queen Mary Hospital; Dept. of Clinical Oncology
• Italy
  • Lombardia
    • Monza, Lombardia, Italy, 20900
      • Recruiting
      • Ospedale San Gerardo; Centro Di Ricerca di Fase I ? Piano 8 ? Settore C
  • Sicilia
    • Palermo, Sicilia, Italy, 90146
      • Recruiting
      • Casa di Cura La Maddalena; Oncologia Medica
• Korea, Republic of
  • Goyang-si, Korea, Republic of, 10408
    • Recruiting
    • National Cancer Center
  • Seoul, Korea, Republic of, 03080
    • Recruiting
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 03722
    • Active, not recruiting
    • Severance Hospital, Yonsei University Health System
  • Seoul, Korea, Republic of, 05505
    • Recruiting
    • Asan Medical Center
  • Seoul, Korea, Republic of, 06273
    • Recruiting
    • Gangnam Severance Hospital
  • Seoul, Korea, Republic of, 06351
    • Recruiting
    • Samsung Medical Center
  • Seoul, Korea, Republic of, 06591
    • Recruiting
    • Seoul St Mary's Hospital
• Poland
  • Konin, Poland, 62-500
    • Recruiting
    • Przychodnia Lekarska KOMED, Roman Karaszewski
  • Koszalin, Poland, 75-581
    • Recruiting
    • Szpital Wojewódzki im. Miko?aja Kopernika; Oddzia? Dzienny Chemioterapii
• Singapore
  • Singapore, Singapore, 119228
    • Recruiting
    • National University Hospital; National University Cancer Institute, Singapore (NCIS)
  • Singapore, Singapore, 308433
    • Recruiting
    • Tan Tock Seng Hospital; Oncology
  • Singapore, Singapore, 217562
    • Recruiting
    • Icon Cancer Centre Farrer Park
  • Singapore, Singapore, 168583
    • Recruiting
    • National Cancer Centre; Medical Oncology
• South Africa
  • Hilton, South Africa, 3245
    • Recruiting
    • Hopelands Cancer Centre
  • Johannesburg, South Africa, 2196
    • Recruiting
    • Medical Oncology Centre of Rosebank; Oncology
  • Johannesburg, South Africa, 2193
    • Recruiting
    • Charlotte Maxeke Academic Hospital
  • Polokwane, South Africa, 0700
    • Recruiting
    • Limpopo Cancer Research Institute
  • Soweto, South Africa, 2013
    • Recruiting
    • Chris Hani Baragwanath Clinical Trial Site
• Spain
  • Barcelona, Spain, 08035
    • Recruiting
    • Hospital Universitari Vall d'Hebron
  • Barcelona, Spain, 08028
    • Recruiting
    • Hospital Universitari Dexeus - Grupo Quironsalud; Servicio de Oncologia Medica
  • Madrid, Spain, 28007
    • Recruiting
    • Hospital General Universitario Gregorio Marañon; Servicio de Oncologia
  • Madrid, Spain, 28034
    • Recruiting
    • Hospital Ramon y Cajal; Servicio de Oncologia
  • Madrid, Spain, 28041
    • Recruiting
    • Hospital Universitario 12 de Octubre; Servicio de Oncologia
  • Malaga, Spain, 29010
    • Recruiting
    • Hospital Clinico Universitario Virgen de la Victoria; Servicio de Oncologia
  • Sevilla, Spain, 41009
    • Recruiting
    • Hospital Universitario Virgen Macarena; Servicio de Oncologia
  • LA Coruña
    • A Coruña, LA Coruña, Spain, 15006
      • Recruiting
      • Complejo Hospitalario Universitario A Coruña (CHUAC); Servicio de Oncologia
• Taiwan
  • Taipei, Taiwan, 100
    • Recruiting
    • National Taiwan Uni Hospital; General Surgery
  • Taipei, Taiwan
    • Recruiting
    • Tri-Service General Hospital; Department of Haematology and Oncology
  • Taoyuan County, Taiwan, 333
    • Recruiting
    • Chang Gung Memorial Hospital-Linkou; Dept of Oncology
• Turkey
  • Istanbul, Turkey, 34214
    • Recruiting
    • Medipol Mega Üniversite Hastanesi Göztepe
• United Kingdom
  • Blackpool, United Kingdom, FY3 8NR
    • Recruiting
    • Blackpool Victoria Hospital
  • Nottingham, United Kingdom, NG5 1PB
    • Recruiting
    • Nottingham City Hospital; Oncology
  • Oxford, United Kingdom, OX3 7LJ
    • Recruiting
    • Churchill Hospital; Oxford Cancer and Haematology Centre
• United States
  • Arizona
    • Gilbert, Arizona, United States, 85234
      • Recruiting
      • Banner Health MD Anderson AZ
  • California
    • Burbank, California, United States, 91505
      • Active, not recruiting
      • Disney Family Cancer Center
    • Los Angeles, California, United States, 90064
      • Recruiting
      • Lawrence J. Ellison Institute for Transformative Medicine
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Recruiting
      • Georgetown Uni Hospital; 4-N Main Hospital
  • Maryland
    • Hyattsville, Maryland, United States, 20783
      • Recruiting
      • Medstar Research Institute
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Recruiting
      • Dana Farber Cancer Institute
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Recruiting
      • Hackensack University Medical Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73102
      • Recruiting
      • Hightower Clinical
  • Texas
    • Kingwood, Texas, United States, 77339
      • Recruiting
      • Lumi Research
  • Washington
    • Kennewick, Washington, United States, 99336-7774
      • Recruiting
      • Kadlec Clinic Hematology and Oncology
    • Seattle, Washington, United States, 98104-1360
      • Recruiting
      • Swedish Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1
• Histologically or cytologically confirmed and documented adenocarcinoma of the breast with metastatic or locally advanced disease not amenable to curative resection
• Confirmation of HER2 biomarker eligibility based on valid results from central testing of tumor tissue documenting HER2-positivity
• Confirmation of PIK3CA-mutation biomarker eligibility based on valid results from central testing of tumor tissue documenting PIK3CA-mutated tumor status
• Disease-free interval from completion of adjuvant or neoadjuvant systemic non-hormonal treatment to recurrence of >= 6 months
• LVEF (left ventricular ejection fraction) of at least 50% measured by echocardiogram (ECHO) or multiple-gated acquisition scan (MUGA)
• Adequate hematologic and organ function prior to initiation of study treatment

Exclusion Criteria:

• Prior treatment in the locally advanced or metastatic setting with any PI3K, AKT, or mTOR inhibitor or any agent whose mechanism of action is to inhibit the PI3K-AKT-mTOR pathway
• Any prior systemic non-hormonal anti-cancer therapy for locally advanced or metastatic HER2-positive breast cancer prior to initiation of induction therapy
• History or active inflammatory bowel disease
• Disease progression within 6 months of receiving any HER2-targeted therapy
• Type 2 diabetes requiring ongoing systemic treatment at the time of study entry; or any history of Type 1 diabetes
• Participants with active HBV infection
• Clinically significant and active liver disease, including severe liver impairment, viral or other hepatitis, current alcohol abuse, or cirrhosis
• Symptomatic active lung disease, including pneumonitis or interstitial lung disease
• Any history of leptomeningeal disease or carcinomatous meningitis
• Serious infection requiring IV antibiotics within 7 days prior to Day 1 of Cycle 1
• Any concurrent ocular or intraocular condition that, in the opinion of the investigator, would require medical or surgical intervention during the study period to prevent or treat vision loss that might result from that condition
• Active inflammatory or infectious conditions in either eye or history of idiopathic or autoimmune-associated uveitis in either eye

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Induction Therapy: Phesgo plus Taxane-Based Chemotherapy; Participants will be administered the treatments as outlined in the interventions section.	Drug: Phesgo; Phesgo will be administered to participants subcutaneously every 3 weeks (Q3W) on D1 of each 21-day cycle.; Drug: Taxane-based Chemotherapy; During the induction therapy phase, the investigator's choice of taxane-based chemotherapy will be administered after Phesgo.; Other Names: non-investigational medicinal product (NIMP)
Experimental: Maintenance Therapy: Inavolisib plus Phesgo; Participants will be administered the treatments as outlined in the interventions section.	Drug: Phesgo; Phesgo will be administered to participants subcutaneously every 3 weeks (Q3W) on D1 of each 21-day cycle.; Drug: Inavolisib; Participants will receive an inavolisib tablet to be taken orally (PO), once a day (QD), on Days 1-21 of each 21-day cycle, beginning on Day (D) 1 of Cycle (C) 1 of maintenance treatment.; Drug: Optional Endocrine Therapy of Investigator's Choice; Optional endocrine therapy (ET) is allowed at the discretion of the investigator, based on the standard of care. Allowed ETs are tamoxifen, or one of the specified third-generation aromatase inhibitor (AI [anastrozole, letrozole, or exemestane]), or fulvestrant. The investigator will determine and supply the appropriate luteinizing hormone-releasing hormone (LHRH) agonist locally approved for use in breast cancer. The LHRH agonist will be administered according to local prescribing information.; Other Names: NIMP
Active Comparator: Maintenance Therapy: Placebo plus Phesgo; Participants will be administered the treatments as outlined in the interventions section.	Drug: Phesgo; Phesgo will be administered to participants subcutaneously every 3 weeks (Q3W) on D1 of each 21-day cycle.; Drug: Optional Endocrine Therapy of Investigator's Choice; Optional endocrine therapy (ET) is allowed at the discretion of the investigator, based on the standard of care. Allowed ETs are tamoxifen, or one of the specified third-generation aromatase inhibitor (AI [anastrozole, letrozole, or exemestane]), or fulvestrant. The investigator will determine and supply the appropriate luteinizing hormone-releasing hormone (LHRH) agonist locally approved for use in breast cancer. The LHRH agonist will be administered according to local prescribing information.; Other Names: NIMP; Drug: Placebo; Inavolisib-matching tablet taken PO QD on Days 1-21 of each 21-day cycle, beginning on D1 C1 of maintenance treatment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Investigator-Assessed Progression-Free Survival (PFS)	Up to approximately 40 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)		Up to approximately 111 months
Investigator-Assessed Objective Response Rate (ORR)		Up to approximately 111 months
Investigator-Assessed Duration of Response (DOR)		Up to approximately 111 months
Investigator-Assessed Clinical Benefit Rate (CBR)		Up to approximately 111 months
Investigator-Assessed PFS2		Up to approximately 111 months
Mean and Mean Changes from Baseline Score in Function and Health-Related Quality of Life (HRQoL)	Assessed through the use of the Functional (Role, Physical) and Global Health Status (GHS)/Quality of Life (QoL) scales of the European Organisation for Research and Treatment of Cancer Quality of Life-Core 30 Questionnaire (EORTC QLQ-C30)	Day 1 of Cycles 1 and 2 and beyond, 30-day safety follow up visit, post-treatment tumor assessment follow-up with PRO collection and survival follow up visit every 6 months (up to 111 months). Each cycle is 21 days.
Percentage of Participants with Adverse Events		Day 1 until 30 days after the final dose of study treatment (up to approximately 111 months). Each cycle is 21 days.
Plasma Concentration of Inavolisib at Specified Timepoints		Day 1 of Cycles 1 and 4. Each cycle is 21 days.

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche
• Investigators: Study Director: Clinical Trials, Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Actual): July 28, 2023
• Primary Completion (Estimated): October 31, 2028
• Study Completion (Estimated): October 31, 2028

Study Registration Dates

• First Submitted: May 24, 2023
• First Submitted That Met QC Criteria: June 7, 2023
• First Posted (Actual): June 8, 2023

Study Record Updates

• Last Update Posted (Actual): April 18, 2024
• Last Update Submitted That Met QC Criteria: April 17, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Phosphoinositide-3 Kinase Inhibitors; Taxane; Inavolisib
• Other Study ID Numbers: WO44263; 2022-502046-28-00 (Registry Identifier: EU Clinical Trials)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/innovation/process/clinical-trials/data-sharing/).

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No