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

Metastatic Breast Cancer Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05894239
• Other study ID #: WO44263
• Secondary ID: 2022-502046-28-0
• Status: Recruiting
• Phase: Phase 3
• Start date: July 28, 2023
• Est. completion date: October 31, 2028

Study information

• Verified date: June 2024
• Source: Hoffmann-La Roche
• Contact: Reference Study ID Number: WO44263 https://forpatients.roche.com
• Phone: 888-662-6728 (U.S. Only)
• Email: global-roche-genentech-trials[@]gene.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 230
• Est. completion date: October 31, 2028
• Est. primary completion date: October 31, 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Neoplasms
• Metastatic Breast Cancer

Intervention

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.
• Phesgo
Phesgo will be administered to participants subcutaneously every 3 weeks (Q3W) on D1 of each 21-day cycle.
• Placebo
Inavolisib-matching tablet taken PO QD on Days 1-21 of each 21-day cycle, beginning on D1 C1 of maintenance treatment.
• Taxane-based Chemotherapy
During the induction therapy phase, the investigator's choice of taxane-based chemotherapy will be administered after Phesgo.
• 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.

Locations

Country	Name	City	State
Argentina	Fundación CENIT para la Investigación en Neurociencias	Buenos Aires
Argentina	Centro Oncologico Korben; Oncology	Ciudad Autonoma Buenos Aires
Argentina	Hospital Provincial del Centenario	Rosario
Argentina	Instituto de Oncología de Rosario	Rosario
Argentina	CER San Juan Centro Polivalente de Asistencia e Investigacion Clinica	San Juan
Australia	Kinghorn Cancer Centre; St Vincents Hospital	Darlinghurst	New South Wales
Australia	Gosford Hospital; Cancer Care Services	Gosford	New South Wales
Australia	Sir Charles Gairdner Hospital; Medical Oncology	Perth	Western Australia
Australia	University of the Sunshine Coast	Sippy Downs	Queensland
Belgium	Cliniques Universitaires St-Luc	Bruxelles
Belgium	GHdC Site Notre Dame	Charleroi
Belgium	Jessa Zkh (Campus Virga Jesse)	Hasselt
Belgium	Clinique Ste-Elisabeth	Namur
Brazil	Hospital de Cancer de Barretos	Barretos	SP
Brazil	Crio - Centro Regional Integrado de Oncologia	Fortaleza	CE
Brazil	Hospital Araujo Jorge; Departamento de Ginecologia E Mama	Goiania	GO
Brazil	Hospital do Câncer de Londrina	Londrina	PR
Brazil	Hospital Sao Lucas - PUCRS	Porto Alegre	RS
Brazil	Santa Casa de Misericordia de Porto Alegre	Porto Alegre	RS
Brazil	Hospital de Amor Amazônia	Porto Velho	RO
Brazil	Hospital do Cancer de Pernambuco - HCP	Recife	PE
Brazil	Clinica de Pesquisa e Centro de Estudos em Oncologia Ginecologica e Mamaria Ltda	Sao Paulo	SP
Brazil	Instituto do Cancer do Estado de Sao Paulo - ICESP	Sao Paulo	SP
Canada	Tom Baker Cancer Centre; Dept of Pathology	Calgary	Alberta
Canada	The Moncton Hospital	Moncton	New Brunswick
Canada	Hôpital du Sacré-Coeur de Montreal	Montreal	Quebec
Canada	Jewish General Hospital	Montreal	Quebec
Canada	Hopital du Saint Sacrement	Quebec City	Quebec
Canada	Allan Blair Cancer Center	Regina	Saskatchewan
Canada	Eastern Health - General Hospital	St. John's	Newfoundland and Labrador
China	Affiliated Hospital of Hebei University; Department of medical oncology	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	The Second Affiliated Hospital of Zhejiang University School of Medicine	Hangzhou City
China	Zhejiang Cancer Hospital; Breast Surgery	Hangzhou City
China	Harbin Medical University Tumor Hospital; Department of Surgery; Pharmacy	Harbin
China	Shandong Cancer Hospital	Jinan
China	The First Affiliated Hospital to Henan University of Science and Technology	Luoyang City
China	The Second Affiliated Hospital to Nanchang University	Nanchang
China	Guangxi Cancer Hospital of Guangxi Medical University	Nanning City
China	Shantou Center Hospital	Shantou City
China	Tianjin Cancer Hospital; Department of Breast Oncology	Tianjin
China	Hubei Cancer Hospital	Wuhan
China	Union Hospital Tongji Medical College Huazhong University of Science and Technology	Wuhan City
Colombia	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
Finland	Tampere University Hospital; Dept of Oncology	Tampere
Finland	Turku Uni Central Hospital; Oncology Clinics	Turku
France	Institut Sainte Catherine	Avignon
France	Centre Hospitalier de La Cote Basque; Oncologie	Bayonne
France	Polyclinique Bordeaux Nord Aquitaine	Bordeaux
Germany	Klinikum St. Marien; Frauenklinik	Amberg
Germany	Marienhospital Bottrop gGmbH; Department of Gynecology and Obstetrics	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	Caritas Klinik St. Theresia -Frauenklinik Brustzentrum	Saarbruecken
Germany	Gynäkologie Kompetenzzentrum; Praxis Dr. med. Carsten Hielscher	Stralsund
Hong Kong	Queen Mary Hospital; Dept. of Clinical Oncology	Hong Kong
Hong Kong	Tuen Mun Hospital; Clinical Oncology	Hong Kong
India	Artemis Hospital	Gurugram	Haryana
India	Tata Medical Center	Kolkata	WEST Bengal
India	Sunshine Global Hospital (A unit of Baroda Medicare Pvt Ltd)	Surat CITY	Gujarat
Italy	Ospedale Santa Maria Annunziata; Oncologia	Bagno a Ripoli	Toscana
Italy	I.R.S.T Srl IRCCS; Oncologia Medica	Meldola	Emilia-Romagna
Italy	Irccs Istituto Europeo Di Oncologia (IEO); Ricerca Di Senologia Medica	Milano	Lombardia
Italy	Ospedale San Raffaele; Medical Oncology	Milano	Lombardia
Italy	Ospedale San Gerardo; Centro Di Ricerca di Fase I ? Piano 8 ? Settore C	Monza	Lombardia
Italy	A.O.U. Maggiore della Carità	Novara	Piemonte
Italy	Casa di Cura La Maddalena; Oncologia Medica	Palermo	Sicilia
Italy	Ospedale San Giovanni Addolorata; Oncologia	Roma	Lazio
Italy	"Azienda Ospedaliera Universitaria Integrata Verona Ospedale Borgo Trento"	Verona	Veneto
Korea, Republic of	National Cancer Center	Goyang-si
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 National University Hospital	Seoul
Korea, Republic of	Seoul St Mary's Hospital	Seoul
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul
Mexico	Hospital Zambrano Hellion TecSalud	Monterrey	Nuevo LEON
Poland	Centrum Onkologii im. Prof. Franciszka ?ukaszczyka; Ambulatorium Chemioterapii	Bydgoszcz
Poland	Uniwersyteckie Centrum Kliniczne; Klinika Onkologii i Radioterapii	Gdansk
Poland	Szpital Morski im.PCK; Oddzial Onkologii Klinicznej, Oddzial Dzienny	Gdynia
Poland	Narodowy Instytut Onkologii Odzia? w Gliwicach; Centrum Diagnostyki i Leczenia Chorób Piersi	Gliwice
Poland	Przychodnia Lekarska KOMED, Roman Karaszewski	Konin
Poland	Szpital Wojewódzki im. Miko?aja Kopernika; Oddzia? Dzienny Chemioterapii	Koszalin
Poland	Centrum Onkologii Instytut im.M. Sklodowskiej-Curie; Klin. Nowot. Piersii i Chirurgii Rekonstruk	Warszawa
Singapore	Icon Cancer Centre Farrer Park	Singapore
Singapore	National Cancer Centre; Medical Oncology	Singapore
Singapore	National University Hospital; National University Cancer Institute, Singapore (NCIS)	Singapore
Singapore	Tan Tock Seng Hospital; Oncology	Singapore
South Africa	Hopelands Cancer Centre	Hilton
South Africa	Charlotte Maxeke Academic Hospital	Johannesburg
South Africa	Medical Oncology Centre of Rosebank; Oncology	Johannesburg
South Africa	Limpopo Cancer Research Institute	Polokwane
South Africa	Chris Hani Baragwanath Clinical Trial Site	Soweto
Spain	Complejo Hospitalario Universitario A Coruña (CHUAC); Servicio de Oncologia	A Coruña	LA Coruña
Spain	Hospital Universitari Dexeus - Grupo Quironsalud; Servicio de Oncologia Medica	Barcelona
Spain	Hospital Universitari Vall d'Hebron	Barcelona
Spain	Hospital General Universitario Gregorio Marañon; Servicio de Oncologia	Madrid
Spain	Hospital Ramon y Cajal; Servicio de Oncologia	Madrid
Spain	Hospital Universitario 12 de Octubre; Servicio de Oncologia	Madrid
Spain	Hospital Clinico Universitario Virgen de la Victoria; Servicio de Oncologia	Malaga
Spain	Hospital Universitario Virgen Macarena; Servicio de Oncologia	Sevilla
Taiwan	National Taiwan Uni Hospital; General Surgery	Taipei
Taiwan	Tri-Service General Hospital; Department of Haematology and Oncology	Taipei
Taiwan	Chang Gung Memorial Hospital-Linkou; Dept of Oncology	Taoyuan County
Turkey	Gazi University Medical Faculty	Ankara
Turkey	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	Medical Park Seyhan Hospital; Oncology Department	Seyhan
Turkey	Hacettepe Uni Medical Faculty Hospital; Oncology Dept	Sihhiye/Ankara
United Kingdom	Blackpool Victoria Hospital	Blackpool
United Kingdom	Nottingham City Hospital; Oncology	Nottingham
United Kingdom	Churchill Hospital; Oxford Cancer and Haematology Centre	Oxford
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Disney Family Cancer Center	Burbank	California
United States	Atrium Health	Charlotte	North Carolina
United States	Banner Health MD Anderson AZ	Gilbert	Arizona
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	Medstar Research Institute	Hyattsville	Maryland
United States	Kadlec Clinic Hematology and Oncology	Kennewick	Washington
United States	Lumi Research	Kingwood	Texas
United States	Lawrence J. Ellison Institute for Transformative Medicine	Los Angeles	California
United States	Hightower Clinical	Oklahoma City	Oklahoma
United States	Swedish Medical Center	Seattle	Washington
United States	Georgetown Uni Hospital; 4-N Main Hospital	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Belgium,  Brazil,  Canada,  China,  Colombia,  Finland,  France,  Germany,  Hong Kong,  India,  Italy,  Korea, Republic of,  Mexico,  Poland,  Singapore,  South Africa,  Spain,  Taiwan,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Investigator-Assessed Progression-Free Survival (PFS)		Up to approximately 40 months
Secondary	Overall Survival (OS)		Up to approximately 111 months
Secondary	Investigator-Assessed Objective Response Rate (ORR)		Up to approximately 111 months
Secondary	Investigator-Assessed Duration of Response (DOR)		Up to approximately 111 months
Secondary	Investigator-Assessed Clinical Benefit Rate (CBR)		Up to approximately 111 months
Secondary	Investigator-Assessed PFS2		Up to approximately 111 months
Secondary	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.
Secondary	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.
Secondary	Plasma Concentration of Inavolisib at Specified Timepoints		Day 1 of Cycles 1 and 4. Each cycle is 21 days.