Clinical trial NCT05894239: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Metastatic Breast Cancer
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2023-06-08
Enrollment: 230
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility criteria: 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

Primary outcomes:
measure: Investigator-Assessed Progression-Free Survival (PFS)
timeFrame: Up to approximately 40 months
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: Up to approximately 111 months
measure: Investigator-Assessed Objective Response Rate (ORR)
timeFrame: Up to approximately 111 months
measure: Investigator-Assessed Duration of Response (DOR)
timeFrame: Up to approximately 111 months
measure: Investigator-Assessed Clinical Benefit Rate (CBR)
timeFrame: Up to approximately 111 months
measure: Investigator-Assessed PFS2
timeFrame: Up to approximately 111 months
measure: Mean and Mean Changes from Baseline Score in Function and Health-Related Quality of Life (HRQoL)
timeFrame: 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.
measure: Percentage of Participants with Adverse Events
timeFrame: Day 1 until 30 days after the final dose of study treatment (up to approximately 111 months). Each cycle is 21 days.
measure: Plasma Concentration of Inavolisib at Specified Timepoints
timeFrame: Day 1 of Cycles 1 and 4. Each cycle is 21 days.
Other outcomes:
Locations:
city: Gilbert
country: United States
facility: Banner Health MD Anderson AZ
state: Arizona
city: Burbank
country: United States
facility: Disney Family Cancer Center
state: California
city: Los Angeles
country: United States
facility: Ellison Institute of Technology
state: California
city: Washington
country: United States
facility: Georgetown Uni Hospital
state: District of Columbia
city: Hyattsville
country: United States
facility: Medstar Research Institute
state: Maryland
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Reno
country: United States
facility: Renown Regional Medical Center
state: Nevada
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Charlotte
country: United States
facility: Atrium Health
state: North Carolina
city: Oklahoma City
country: United States
facility: Hightower Clinical
state: Oklahoma
city: El Paso
country: United States
facility: Renovatio Clinical - El Paso
state: Texas
city: Fort Worth
country: United States
facility: JPS Health Network
state: Texas
city: Kingwood
country: United States
facility: Lumi Research
state: Texas
city: The Woodlands
country: United States
facility: Renovatio Clinical
state: Texas
city: Kennewick
country: United States
facility: Kadlec Clinic Hematology and Oncology
state: Washington
city: Seattle
country: United States
facility: Swedish Medical Center
state: Washington
city: Buenos Aires
country: Argentina
facility: Fundación CENIT para la Investigación en Neurociencias
city: Ciudad Autonoma Buenos Aires
country: Argentina
facility: Centro Oncologico Korben
city: Rosario
country: Argentina
facility: Instituto de Oncología de Rosario
city: Rosario
country: Argentina
facility: Hospital Provincial del Centenario
city: San Juan
country: Argentina
facility: CER San Juan Centro Polivalente de Asistencia e Investigacion Clinica
city: Viedma Rio Negro
country: Argentina
facility: Clínica Viedma
city: Blacktown
country: Australia
facility: Blacktown Hospital
state: New South Wales
city: Darlinghurst
country: Australia
facility: Kinghorn Cancer Centre
state: New South Wales
city: Gosford
country: Australia
facility: Gosford Hospital
state: New South Wales
city: Sippy Downs
country: Australia
facility: University of the Sunshine Coast
state: Queensland
city: Clayton
country: Australia
facility: Monash Health
state: Victoria
city: Perth
country: Australia
facility: Sir Charles Gairdner Hospital
state: Western Australia
city: Bruxelles
country: Belgium
facility: Cliniques Universitaires St-Luc
city: Charleroi
country: Belgium
facility: GHdC Site Les Viviers
city: Hasselt
country: Belgium
facility: Jessa Zkh (Campus Virga Jesse)
city: Namur
country: Belgium
facility: Clinique Ste-Elisabeth
city: Salvador
country: Brazil
facility: Hospital Sao Rafael - HSR
state: Bahia
city: Fortaleza
country: Brazil
facility: Crio - Centro Regional Integrado de Oncologia
state: Ceará
city: Goiania
country: Brazil
facility: Hospital Araujo Jorge
state: Goiás
city: Londrina
country: Brazil
facility: Hospital do Câncer de Londrina
state: Paraná
city: Recife
country: Brazil
facility: Hospital do Cancer de Pernambuco - HCP
state: Pernambuco
city: Porto Alegre
country: Brazil
facility: Santa Casa de Misericordia de Porto Alegre
state: Rio Grande Do Sul
city: Porto Alegre
country: Brazil
facility: Hospital Sao Lucas - PUCRS
state: Rio Grande Do Sul
city: Porto Velho
country: Brazil
facility: Hospital de Amor Amazônia
state: Rondônia
city: Barretos
country: Brazil
facility: Hospital de Cancer de Barretos
state: São Paulo
city: Sao Paulo
country: Brazil
facility: Instituto do Cancer do Estado de Sao Paulo - ICESP
state: São Paulo
city: Sao Paulo
country: Brazil
facility: Clinica de Pesquisa e Centro de Estudos em Oncologia Ginecologica e Mamaria Ltda
state: São Paulo
city: Calgary
country: Canada
facility: Arthur J.E. Child Comprehensive Cancer Center-Calgary
state: Alberta
city: Moncton
country: Canada
facility: The Moncton Hospital
state: New Brunswick
city: St. John's
country: Canada
facility: Eastern Health - General Hospital
state: Newfoundland and Labrador
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
city: Montreal
country: Canada
facility: Centre Hospitalier de l?Université de Montréal (CHUM)
state: Quebec
city: Montreal
country: Canada
facility: Jewish General Hospital
state: Quebec
city: Montreal
country: Canada
facility: Hôpital du Sacré-Coeur de Montreal
state: Quebec
city: Quebec City
country: Canada
facility: Hopital du Saint Sacrement
state: Quebec
city: Regina
country: Canada
facility: Allan Blair Cancer Center
state: Saskatchewan
city: Baoding
country: China
facility: Affiliated Hospital of Hebei University
city: Beijing
country: China
facility: Beijing Cancer Hospital
city: Changchun City
country: China
facility: The First Hospital of Jilin University
city: Chengdu
country: China
facility: Sichuan Provincial Cancer Hospital
city: Chengdu
country: China
facility: Sichuan Provincial People's Hospital
city: Fuzhou
country: China
facility: Fujian Cancer Hospital
city: Hangzhou City
country: China
facility: Zhejiang Cancer Hospital
city: Harbin
country: China
facility: Harbin Medical University Tumor Hospital
city: Jinan
country: China
facility: Shandong Cancer Hospital
city: Luoyang
country: China
facility: The First Affiliated Hospital to Henan University of Science and Technology
city: Nanchang
country: China
facility: The Second Affiliated Hospital to Nanchang University
city: Nanning
country: China
facility: Guangxi Cancer Hospital of Guangxi Medical University
city: Shantou City
country: China
facility: Shantou Center Hospital
city: Tianjin
country: China
facility: Tianjin Cancer Hospital
city: Wuhan City
country: China
facility: Union Hospital Tongji Medical College Huazhong University of Science and Technology
city: Wuhan
country: China
facility: Hubei Cancer Hospital
city: Barranquilla
country: Colombia
facility: Clinica De La Costa
city: Bogota, D.C.
country: Colombia
facility: Fundación CTIC - Centro de Tratamiento e Investigación sobre Cáncer Luis Carlos Sarmiento Angulo
city: Monteria
country: Colombia
facility: Oncomedica S.A.
city: Valledupar
country: Colombia
facility: Sociedad de Oncología y hematología del Cesar Ltda
city: Tampere
country: Finland
facility: Tampere University Hospital
city: Turku
country: Finland
facility: Turku Uni Central Hospital
city: Avignon
country: France
facility: Institut Sainte Catherine
city: Bayonne
country: France
facility: Centre Hospitalier de La Cote Basque
city: Bordeaux
country: France
facility: Polyclinique Bordeaux Nord Aquitaine
city: Lille
country: France
facility: Centre Oscar Lambret
city: Amberg
country: Germany
facility: Klinikum St. Marien
city: Bottrop
country: Germany
facility: Marienhospital Bottrop gGmbH
city: Düsseldorf
country: Germany
facility: Gynonco Düsseldorf, MVZ Medical Center GmbH
city: Erfurt
country: Germany
facility: Frauenarztpraxis Dr. Apel, Dr. Kolpin
city: Freiburg
country: Germany
facility: Praxis für Interdisziplinäre Onkologie und Hämatologie GbR
city: München
country: Germany
facility: Klinik & Poliklinik für Frauenheilkunde und Geburtshilfe, Campus Innenstadt
city: Saarbruecken
country: Germany
facility: Caritas Klinik St. Theresia -Frauenklinik Brustzentrum
city: Stralsund
country: Germany
facility: Gynäkologie Kompetenzzentrum
city: Hong Kong
country: Hong Kong
facility: Queen Mary Hospital
city: Hong Kong
country: Hong Kong
facility: Tuen Mun Hospital
city: NEW Delhi Delhi
country: India
facility: Max Super Speciality Hospital
state: Delhi
city: Ahmadabad CITY
country: India
facility: Gujarat Cancer & Research Inst.
state: Gujarat
city: Surat CITY
country: India
facility: Sunshine Global Hospital (A unit of Baroda Medicare Pvt Ltd)
state: Gujarat
city: Gurugram
country: India
facility: Artemis Hospital
state: Haryana
city: Nagpur
country: India
facility: National Cancer Institute
state: Maharashtra
city: Kolkata
country: India
facility: Tata Medical Center
state: WEST Bengal
city: Meldola
country: Italy
facility: I.R.S.T Srl IRCCS
state: Emilia-Romagna
city: Roma
country: Italy
facility: Ospedale San Giovanni Addolorata
state: Lazio
city: Milano
country: Italy
facility: Ospedale San Raffaele
state: Lombardia
city: Milano
country: Italy
facility: Irccs Istituto Nazionale Dei Tumori (Int)
state: Lombardia
city: Milano
country: Italy
facility: Irccs Istituto Europeo Di Oncologia (IEO)
state: Lombardia
city: Monza
country: Italy
facility: Ospedale San Gerardo
state: Lombardia
city: Novara
country: Italy
facility: A.O.U. Maggiore della Carità
state: Piemonte
city: Palermo
country: Italy
facility: Casa di Cura La Maddalena
state: Sicilia
city: Bagno a Ripoli
country: Italy
facility: Ospedale Santa Maria Annunziata
state: Toscana
city: Verona
country: Italy
facility: "Azienda Ospedaliera Universitaria Integrata Verona Ospedale Borgo Trento"
state: Veneto
city: Amman
country: Jordan
facility: King Hussein Cancer Center
city: Nairobi
country: Kenya
facility: University of Nairobi - Institute of Tropical and Infectious Diseases
city: Goyang-si
country: Korea, Republic of
facility: National Cancer Center
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Gangnam Severance Hospital
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul St Mary's Hospital
city: Guadalajara
country: Mexico
facility: Hospital Civil de Guadalajara Fray Antonio Alcalde
state: Jalisco
city: Ciudad de México
country: Mexico
facility: OncoMed
state: Mexico CITY (federal District)
city: Mexico City
country: Mexico
facility: Centro Oncológico Hematológico Roma
state: Mexico CITY (federal District)
city: Monterrey
country: Mexico
facility: Hospital Universitario
state: Nuevo LEON
city: Mexico City
country: Mexico
facility: CENEIT Oncologicos
city: Muscat
country: Oman
facility: Sultan Qaboos Comprehensive Cancer Care & Research Center
city: Bydgoszcz
country: Poland
facility: Centrum Onkologii im. Prof. Franciszka ?ukaszczyka
city: Gda?sk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne
city: Gdynia
country: Poland
facility: Szpital Morski im.PCK
city: Gliwice
country: Poland
facility: Narodowy Instytut Onkologii Odzia? w Gliwicach
city: Konin
country: Poland
facility: Przychodnia Lekarska KOMED, Roman Karaszewski
city: Koszalin
country: Poland
facility: Szpital Wojewódzki im. Miko?aja Kopernika
city: Pozna?
country: Poland
facility: Wielkopolskie Centrum Onkologii im. Marii Sk?odowskiej-Curie
city: Warszawa
country: Poland
facility: Centrum Onkologii Instytut im.M. Sklodowskiej-Curie
city: Singapore
country: Singapore
facility: National University Hospital
city: Singapore
country: Singapore
facility: National Cancer Centre
city: Singapore
country: Singapore
facility: Icon Cancer Centre Farrer Park
city: Singapore
country: Singapore
facility: Tan Tock Seng Hospital
city: Hilton
country: South Africa
facility: Hopelands Cancer Centre
city: Johannesburg
country: South Africa
facility: Charlotte Maxeke Academic Hospital
city: Johannesburg
country: South Africa
facility: Medical Oncology Centre of Rosebank
city: Polokwane
country: South Africa
facility: Limpopo Cancer Research Institute
city: Pretoria
country: South Africa
facility: Steve Biko Academic Hospital
city: Soweto
country: South Africa
facility: Chris Hani Baragwanath Clinical Trial Site
city: A Coruña
country: Spain
facility: Complejo Hospitalario Universitario A Coruña (CHUAC)
state: LA Coruna
city: Barcelona
country: Spain
facility: Hospital Universitari Dexeus - Grupo Quironsalud
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañon
city: Madrid
country: Spain
facility: Hospital Ramon y Cajal
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Malaga
country: Spain
facility: Hospital Clinico Universitario Virgen de la Victoria
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Macarena
city: Taipei
country: Taiwan
facility: National Taiwan Uni Hospital
city: Taipei
country: Taiwan
facility: Tri-Service General Hospital
city: Taoyuan County
country: Taiwan
facility: Chang Gung Memorial Hospital-Linkou
city: Ariana
country: Tunisia
facility: Abderrahmen Mami Hospital
city: Nabeul
country: Tunisia
facility: Taher Maamouri Hospital
city: Sfax
country: Tunisia
facility: Habib Bourguiba Hospital
city: Sousse
country: Tunisia
facility: Farhat Hached Hospital
city: Tunis
country: Tunisia
facility: Institut Salah Azeiz
city: Adapazar?
country: Turkey
facility: Sakarya Training and Research Hospital
city: Ankara
country: Turkey
facility: Gulhane Training and Research Hospital
city: Ankara
country: Turkey
facility: Gazi University Medical Faculty
city: Bakirkoy / Istanbul
country: Turkey
facility: Bakirkoy Dr. Sadi Konuk Egitim ve Arastirma Hastanesi, Tibbi Onkoloji
city: Diyarbakir
country: Turkey
facility: Dicle University Faculty of Medicine
city: Istanbul
country: Turkey
facility: Medipol Mega Üniversite Hastanesi Göztepe
city: Izmir
country: Turkey
facility: Katip Celebi University Ataturk Training and Research Hospital
city: Seyhan
country: Turkey
facility: Medical Park Seyhan Hospital
city: Sihhiye/Ankara
country: Turkey
facility: Hacettepe Uni Medical Faculty Hospital
city: Kampala
country: Uganda
facility: Uganda Cancer Institute
city: Blackpool
country: United Kingdom
facility: Blackpool Victoria Hospital
city: Colchester, Essex
country: United Kingdom
facility: Colchester General Hospital
city: Northwood
country: United Kingdom
facility: Mount Vernon Hospital
city: Nottingham
country: United Kingdom
facility: Nottingham City Hospital
city: Oxford
country: United Kingdom
facility: Churchill Hospital
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: