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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

Phase 3
Recruiting
Conditions
Metastatic Breast Cancer
Interventions
Drug: Taxane-based Chemotherapy
Drug: Placebo
Drug: Optional Endocrine Therapy of Investigator's Choice
Registration Number
NCT05894239
Lead Sponsor
Hoffmann-La Roche
Brief Summary

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).

Detailed Description

Not available

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
230
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Induction Therapy: Phesgo plus Taxane-Based ChemotherapyPhesgoParticipants will be administered the treatments as outlined in the interventions section.
Induction Therapy: Phesgo plus Taxane-Based ChemotherapyTaxane-based ChemotherapyParticipants will be administered the treatments as outlined in the interventions section.
Maintenance Therapy: Inavolisib plus PhesgoInavolisibParticipants will be administered the treatments as outlined in the interventions section.
Maintenance Therapy: Inavolisib plus PhesgoPhesgoParticipants will be administered the treatments as outlined in the interventions section.
Maintenance Therapy: Inavolisib plus PhesgoOptional Endocrine Therapy of Investigator's ChoiceParticipants will be administered the treatments as outlined in the interventions section.
Maintenance Therapy: Placebo plus PhesgoPhesgoParticipants will be administered the treatments as outlined in the interventions section.
Maintenance Therapy: Placebo plus PhesgoPlaceboParticipants will be administered the treatments as outlined in the interventions section.
Maintenance Therapy: Placebo plus PhesgoOptional Endocrine Therapy of Investigator's ChoiceParticipants will be administered the treatments as outlined in the interventions section.
Primary Outcome Measures
NameTimeMethod
Investigator-Assessed Progression-Free Survival (PFS)Up to approximately 40 months
Secondary Outcome Measures
NameTimeMethod
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 PFS2Up to approximately 111 months
Mean and Mean Changes from Baseline Score in Function and Health-Related Quality of Life (HRQoL)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.

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)

Percentage of Participants with Adverse EventsDay 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 TimepointsDay 1 of Cycles 1 and 4. Each cycle is 21 days.

Trial Locations

Locations (164)

Shandong Cancer Hospital

🇨🇳

Jinan, China

Gazi University Medical Faculty

🇹🇷

Ankara, Turkey

Farhat Hached Hospital

🇹🇳

Sousse, Tunisia

Institut Salah Azeiz

🇹🇳

Tunis, Tunisia

Hubei Cancer Hospital

🇨🇳

Wuhan, China

Banner Health MD Anderson AZ

🇺🇸

Gilbert, Arizona, United States

Disney Family Cancer Center

🇺🇸

Burbank, California, United States

Ellison Institute of Technology

🇺🇸

Los Angeles, California, United States

Georgetown Uni Hospital

🇺🇸

Washington, District of Columbia, United States

Medstar Research Institute

🇺🇸

Hyattsville, Maryland, United States

Dana Farber Cancer Institute

🇺🇸

Boston, Massachusetts, United States

Henry Ford Hospital

🇺🇸

Detroit, Michigan, United States

Renown Regional Medical Center

🇺🇸

Reno, Nevada, United States

Hackensack University Medical Center

🇺🇸

Hackensack, New Jersey, United States

Atrium Health

🇺🇸

Charlotte, North Carolina, United States

Hightower Clinical

🇺🇸

Oklahoma City, Oklahoma, United States

Renovatio Clinical - El Paso

🇺🇸

El Paso, Texas, United States

JPS Health Network

🇺🇸

Fort Worth, Texas, United States

Lumi Research

🇺🇸

Kingwood, Texas, United States

Renovatio Clinical

🇺🇸

The Woodlands, Texas, United States

Kadlec Clinic Hematology and Oncology

🇺🇸

Kennewick, Washington, United States

Swedish Medical Center

🇺🇸

Seattle, Washington, United States

Fundación CENIT para la Investigación en Neurociencias

🇦🇷

Buenos Aires, Argentina

Centro Oncologico Korben

🇦🇷

Ciudad Autonoma Buenos Aires, Argentina

Instituto de Oncología de Rosario

🇦🇷

Rosario, Argentina

Hospital Provincial del Centenario

🇦🇷

Rosario, Argentina

CER San Juan Centro Polivalente de Asistencia e Investigacion Clinica

🇦🇷

San Juan, Argentina

Clínica Viedma

🇦🇷

Viedma Rio Negro, Argentina

Blacktown Hospital

🇦🇺

Blacktown, New South Wales, Australia

Kinghorn Cancer Centre

🇦🇺

Darlinghurst, New South Wales, Australia

Gosford Hospital

🇦🇺

Gosford, New South Wales, Australia

University of the Sunshine Coast

🇦🇺

Sippy Downs, Queensland, Australia

Monash Health

🇦🇺

Clayton, Victoria, Australia

Sir Charles Gairdner Hospital

🇦🇺

Perth, Western Australia, Australia

Cliniques Universitaires St-Luc

🇧🇪

Bruxelles, Belgium

GHdC Site Les Viviers

🇧🇪

Charleroi, Belgium

Jessa Zkh (Campus Virga Jesse)

🇧🇪

Hasselt, Belgium

Clinique Ste-Elisabeth

🇧🇪

Namur, Belgium

Hospital Sao Rafael - HSR

🇧🇷

Salvador, Bahia, Brazil

Crio - Centro Regional Integrado de Oncologia

🇧🇷

Fortaleza, Ceará, Brazil

Hospital Araujo Jorge

🇧🇷

Goiania, Goiás, Brazil

Hospital do Câncer de Londrina

🇧🇷

Londrina, Paraná, Brazil

Hospital do Cancer de Pernambuco - HCP

🇧🇷

Recife, Pernambuco, Brazil

Santa Casa de Misericordia de Porto Alegre

🇧🇷

Porto Alegre, Rio Grande Do Sul, Brazil

Hospital Sao Lucas - PUCRS

🇧🇷

Porto Alegre, Rio Grande Do Sul, Brazil

Hospital de Amor Amazônia

🇧🇷

Porto Velho, Rondônia, Brazil

Hospital de Cancer de Barretos

🇧🇷

Barretos, São Paulo, Brazil

Instituto do Cancer do Estado de Sao Paulo - ICESP

🇧🇷

Sao Paulo, São Paulo, Brazil

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

🇧🇷

Sao Paulo, São Paulo, Brazil

Arthur J.E. Child Comprehensive Cancer Center-Calgary

🇨🇦

Calgary, Alberta, Canada

The Moncton Hospital

🇨🇦

Moncton, New Brunswick, Canada

Eastern Health - General Hospital

🇨🇦

St. John's, Newfoundland and Labrador, Canada

Sunnybrook Health Sciences Centre

🇨🇦

Toronto, Ontario, Canada

Centre Hospitalier de l?Université de Montréal (CHUM)

🇨🇦

Montreal, Quebec, Canada

Jewish General Hospital

🇨🇦

Montreal, Quebec, Canada

Hôpital du Sacré-Coeur de Montreal

🇨🇦

Montreal, Quebec, Canada

Hopital du Saint Sacrement

🇨🇦

Quebec City, Quebec, Canada

Allan Blair Cancer Center

🇨🇦

Regina, Saskatchewan, Canada

Affiliated Hospital of Hebei University

🇨🇳

Baoding, China

Beijing Cancer Hospital

🇨🇳

Beijing, China

The First Hospital of Jilin University

🇨🇳

Changchun City, China

Sichuan Provincial Cancer Hospital

🇨🇳

Chengdu, China

Sichuan Provincial People's Hospital

🇨🇳

Chengdu, China

Fujian Cancer Hospital

🇨🇳

Fuzhou, China

Zhejiang Cancer Hospital

🇨🇳

Hangzhou City, China

Harbin Medical University Tumor Hospital

🇨🇳

Harbin, China

The First Affiliated Hospital to Henan University of Science and Technology

🇨🇳

Luoyang, China

The Second Affiliated Hospital to Nanchang University

🇨🇳

Nanchang, China

Guangxi Cancer Hospital of Guangxi Medical University

🇨🇳

Nanning, China

Shantou Center Hospital

🇨🇳

Shantou City, China

Tianjin Cancer Hospital

🇨🇳

Tianjin, China

Union Hospital Tongji Medical College Huazhong University of Science and Technology

🇨🇳

Wuhan City, China

Clinica De La Costa

🇨🇴

Barranquilla, Colombia

Fundación CTIC - Centro de Tratamiento e Investigación sobre Cáncer Luis Carlos Sarmiento Angulo

🇨🇴

Bogota, D.C., Colombia

Oncomedica S.A.

🇨🇴

Monteria, Colombia

Sociedad de Oncología y hematología del Cesar Ltda

🇨🇴

Valledupar, Colombia

Tampere University Hospital

🇫🇮

Tampere, Finland

Turku Uni Central Hospital

🇫🇮

Turku, Finland

Institut Sainte Catherine

🇫🇷

Avignon, France

Centre Hospitalier de La Cote Basque

🇫🇷

Bayonne, France

Polyclinique Bordeaux Nord Aquitaine

🇫🇷

Bordeaux, France

Centre Oscar Lambret

🇫🇷

Lille, France

Klinikum St. Marien

🇩🇪

Amberg, Germany

Marienhospital Bottrop gGmbH

🇩🇪

Bottrop, Germany

Gynonco Düsseldorf, MVZ Medical Center GmbH

🇩🇪

Düsseldorf, Germany

Frauenarztpraxis Dr. Apel, Dr. Kolpin

🇩🇪

Erfurt, Germany

Praxis für Interdisziplinäre Onkologie und Hämatologie GbR

🇩🇪

Freiburg, Germany

Klinik & Poliklinik für Frauenheilkunde und Geburtshilfe, Campus Innenstadt

🇩🇪

München, Germany

Caritas Klinik St. Theresia -Frauenklinik Brustzentrum

🇩🇪

Saarbruecken, Germany

Gynäkologie Kompetenzzentrum

🇩🇪

Stralsund, Germany

Queen Mary Hospital

🇭🇰

Hong Kong, Hong Kong

Tuen Mun Hospital

🇭🇰

Hong Kong, Hong Kong

Max Super Speciality Hospital

🇮🇳

NEW Delhi Delhi, Delhi, India

Sunshine Global Hospital (A unit of Baroda Medicare Pvt Ltd)

🇮🇳

Surat CITY, Gujarat, India

Artemis Hospital

🇮🇳

Gurugram, Haryana, India

Tata Medical Center

🇮🇳

Kolkata, WEST Bengal, India

I.R.S.T Srl IRCCS

🇮🇹

Meldola, Emilia-Romagna, Italy

Ospedale San Giovanni Addolorata

🇮🇹

Roma, Lazio, Italy

Ospedale San Raffaele

🇮🇹

Milano, Lombardia, Italy

Irccs Istituto Nazionale Dei Tumori (Int)

🇮🇹

Milano, Lombardia, Italy

Irccs Istituto Europeo Di Oncologia (IEO)

🇮🇹

Milano, Lombardia, Italy

Ospedale San Gerardo

🇮🇹

Monza, Lombardia, Italy

A.O.U. Maggiore della Carità

🇮🇹

Novara, Piemonte, Italy

Casa di Cura La Maddalena

🇮🇹

Palermo, Sicilia, Italy

Ospedale Santa Maria Annunziata

🇮🇹

Bagno a Ripoli, Toscana, Italy

"Azienda Ospedaliera Universitaria Integrata Verona Ospedale Borgo Trento"

🇮🇹

Verona, Veneto, Italy

King Hussein Cancer Center

🇯🇴

Amman, Jordan

University of Nairobi - Institute of Tropical and Infectious Diseases

🇰🇪

Nairobi, Kenya

National Cancer Center

🇰🇷

Goyang-si, Korea, Republic of

Seoul National University Hospital

🇰🇷

Seoul, Korea, Republic of

Severance Hospital, Yonsei University Health System

🇰🇷

Seoul, Korea, Republic of

Asan Medical Center

🇰🇷

Seoul, Korea, Republic of

Gangnam Severance Hospital

🇰🇷

Seoul, Korea, Republic of

Samsung Medical Center

🇰🇷

Seoul, Korea, Republic of

Seoul St Mary's Hospital

🇰🇷

Seoul, Korea, Republic of

Hospital Civil de Guadalajara Fray Antonio Alcalde

🇲🇽

Guadalajara, Jalisco, Mexico

OncoMed

🇲🇽

Ciudad de México, Mexico CITY (federal District), Mexico

Centro Oncológico Hematológico Roma

🇲🇽

Mexico City, Mexico CITY (federal District), Mexico

Hospital Universitario

🇲🇽

Monterrey, Nuevo LEON, Mexico

CENEIT Oncologicos

🇲🇽

Mexico City, Mexico

Sultan Qaboos Comprehensive Cancer Care & Research Center

🇴🇲

Muscat, Oman

Centrum Onkologii im. Prof. Franciszka ?ukaszczyka

🇵🇱

Bydgoszcz, Poland

Uniwersyteckie Centrum Kliniczne

🇵🇱

Gda?sk, Poland

Szpital Morski im.PCK

🇵🇱

Gdynia, Poland

Narodowy Instytut Onkologii Odzia? w Gliwicach

🇵🇱

Gliwice, Poland

Przychodnia Lekarska KOMED, Roman Karaszewski

🇵🇱

Konin, Poland

Szpital Wojewódzki im. Miko?aja Kopernika

🇵🇱

Koszalin, Poland

Wielkopolskie Centrum Onkologii im. Marii Sk?odowskiej-Curie

🇵🇱

Pozna?, Poland

Centrum Onkologii Instytut im.M. Sklodowskiej-Curie

🇵🇱

Warszawa, Poland

National University Hospital

🇸🇬

Singapore, Singapore

National Cancer Centre

🇸🇬

Singapore, Singapore

Icon Cancer Centre Farrer Park

🇸🇬

Singapore, Singapore

Tan Tock Seng Hospital

🇸🇬

Singapore, Singapore

Hopelands Cancer Centre

🇿🇦

Hilton, South Africa

Charlotte Maxeke Academic Hospital

🇿🇦

Johannesburg, South Africa

Medical Oncology Centre of Rosebank

🇿🇦

Johannesburg, South Africa

Limpopo Cancer Research Institute

🇿🇦

Polokwane, South Africa

Steve Biko Academic Hospital

🇿🇦

Pretoria, South Africa

Chris Hani Baragwanath Clinical Trial Site

🇿🇦

Soweto, South Africa

Complejo Hospitalario Universitario A Coruña (CHUAC)

🇪🇸

A Coruña, LA Coruna, Spain

Hospital Universitari Dexeus - Grupo Quironsalud

🇪🇸

Barcelona, Spain

Hospital Universitari Vall d'Hebron

🇪🇸

Barcelona, Spain

Hospital General Universitario Gregorio Marañon

🇪🇸

Madrid, Spain

Hospital Ramon y Cajal

🇪🇸

Madrid, Spain

Hospital Universitario 12 de Octubre

🇪🇸

Madrid, Spain

Hospital Clinico Universitario Virgen de la Victoria

🇪🇸

Malaga, Spain

Hospital Universitario Virgen Macarena

🇪🇸

Sevilla, Spain

National Taiwan Uni Hospital

🇨🇳

Taipei, Taiwan

Tri-Service General Hospital

🇨🇳

Taipei, Taiwan

Chang Gung Memorial Hospital-Linkou

🇨🇳

Taoyuan County, Taiwan

Abderrahmen Mami Hospital

🇹🇳

Ariana, Tunisia

Habib Bourguiba Hospital

🇹🇳

Sfax, Tunisia

Bakirkoy Dr. Sadi Konuk Egitim ve Arastirma Hastanesi, Tibbi Onkoloji

🇹🇷

Bakirkoy / Istanbul, Turkey

Dicle University Faculty of Medicine

🇹🇷

Diyarbakir, Turkey

Medipol Mega Üniversite Hastanesi Göztepe

🇹🇷

Istanbul, Turkey

Katip Celebi University Ataturk Training and Research Hospital

🇹🇷

Izmir, Turkey

Medical Park Seyhan Hospital

🇹🇷

Seyhan, Turkey

Hacettepe Uni Medical Faculty Hospital

🇹🇷

Sihhiye/Ankara, Turkey

Uganda Cancer Institute

🇺🇬

Kampala, Uganda

Blackpool Victoria Hospital

🇬🇧

Blackpool, United Kingdom

Colchester General Hospital

🇬🇧

Colchester, Essex, United Kingdom

Mount Vernon Hospital

🇬🇧

Northwood, United Kingdom

Nottingham City Hospital

🇬🇧

Nottingham, United Kingdom

Churchill Hospital

🇬🇧

Oxford, United Kingdom

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