A Study Evaluating the Efficacy and Safety of Inavolisib Plus Fulvestrant Compared With Alpelisib Plus Fulvestrant in Participants With HR-Positive, HER2-Negative, PIK3CA Mutated, Locally Advanced or Metastatic Breast Cancer Post CDK4/6i and Endocrine Combination Therapy (INAVO121)

A Phase III, Multicenter, Randomized, Open-Label Study Evaluating the Efficacy and Safety of Inavolisib Plus Fulvestrant Versus Alpelisib Plus Fulvestrant in Patients With Hormone Receptor-Positive, HER2-Negative, PIK3CA Mutated, Locally Advanced or Metastatic Breast Cancer Who Progressed During or After CDK4/6 Inhibitor and Endocrine Combination Therapy

This is a Phase III, multicenter, randomized, open-label, global study designed to evaluate the efficacy and safety of inavolisib plus fulvestrant compared with alpelisib plus fulvestrant in patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2) -negative, PIK3CA-mutated, locally advanced (LA) or metastatic breast cancer (mBC), who progressed during or after cyclin dependent kinase 4/6i (CDK4/6i)-based therapy.

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Inavolisib; Drug: Fulvestrant; Drug: Alpelisib

• Study Type: Interventional
• Enrollment (Estimated): 400
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Reference Study ID Number: WO43919 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
  • La Rioja, Argentina, F5300COE
    • Active, not recruiting
    • Fundación CORI para la Investigación y Prevención del Cáncer
  • Rosario, Argentina, S2000KZE
    • Recruiting
    • Instituto de Oncologia de Rosario
  • Rosario, Argentina, S2000QGB
    • Recruiting
    • Sanatorio Parque S.A.
  • Rosario, Argentina, S2002KDS
    • Active, not recruiting
    • Hosp Provincial D. Centenarios; Oncology Dept
  • San Juan, Argentina, J5400DIL
    • Recruiting
    • CER San Juan Centro Polivalente de Asistencia e Investigacion Clinica
  • Viedma, Argentina, R8500ACE
    • Recruiting
    • Clinica Viedma S.A.
• Australia
  • New South Wales
    • Campbelltown, New South Wales, Australia, 2560
      • Recruiting
      • Campbelltown Hospital; Macarthur Cancer Therapy Centre
    • Coffs Harbour, New South Wales, Australia, 2450
      • Recruiting
      • Coffs Harbour Health Campus
    • Concord, New South Wales, Australia, 2139
      • Recruiting
      • Concord Repatriation General Hospital; Concord Cancer Centre
    • 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
    • Auchenflower, Queensland, Australia, 4066
      • Recruiting
      • Icon Cancer Care Wesley
    • Sippy Downs, Queensland, Australia, 4556
      • Recruiting
      • University of the Sunshine Coast
  • Victoria
    • Bendigo, Victoria, Australia, 3550
      • Recruiting
      • Bendigo Cancer Centre
  • 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
  • Edegem, Belgium, 2650
    • Recruiting
    • UZ Antwerpen
  • Gent, Belgium, 9000
    • Recruiting
    • UZ Gent
  • Leuven, Belgium, 3000
    • Recruiting
    • UZ Leuven Gasthuisberg
  • Namur, Belgium, 5000
    • Recruiting
    • Clinique Ste-Elisabeth
• Brazil
  • DF
    • Brasilia, DF, Brazil, 70390-140
      • Recruiting
      • Instituto D?Or de Pesquisa e Ensino ? Hospital DF STAR
  • PR
    • Curitiba, PR, Brazil, 80420-090
      • Recruiting
      • Hospital Santa Cruz / Centro de Oncologia D'Or
  • RN
    • Natal, RN, Brazil, 59040150
      • Recruiting
      • Liga Norte Riograndense Contra O Câncer
  • 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
    • Sao Jose do Rio Preto, SP, Brazil, 15090-000
      • Recruiting
      • Hospital de Base de São José do Rio Preto
    • Sao Paulo, SP, Brazil, 01308-050
      • Recruiting
      • Hospital Sirio-Libanes
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N2
      • Recruiting
      • Tom Baker Cancer Centre-Calgary
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Recruiting
      • Cross Cancer Institute
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 4E6
      • Recruiting
      • BC Cancer ? Vancouver
  • New Brunswick
    • Moncton, New Brunswick, Canada, E1C 6Z8
      • Recruiting
      • The Moncton Hospital
  • Ontario
    • Hamilton, Ontario, Canada, L8V 1C3
      • Recruiting
      • Juravinski Hospital
    • Ottawa, Ontario, Canada, K1H 8L6
      • Recruiting
      • The Ottawa Hospital - General Campus
  • Quebec
    • Montreal, Quebec, Canada, H3T 1E2
      • Recruiting
      • Jewish General Hospital
    • Montreal, Quebec, Canada, H4J 1C5
      • Recruiting
      • Hôpital du Sacré-Coeur de Montreal
    • Montreal, Quebec, Canada, H2X 0C1
      • Recruiting
      • Centre Hospitalier de l'Université de Montréal (CHUM)
    • Montreal, Quebec, Canada, H1T 2M4
      • Recruiting
      • CIUSSS de l Est de l Ile de Montreal - Hopital Maisonneuve Rosemont
• China
  • Changchun City, China, 130021
    • Recruiting
    • The First Hospital of Jilin University
  • Chengdu, China, 610041
    • Recruiting
    • Sichuan Provincial Cancer Hospital
  • Chongqing, China, 400016
    • Recruiting
    • The First Affiliated Hospital, Chongqing Medical University
  • Guangzhou, China, 510060
    • Recruiting
    • Sun yat-sen University Cancer Center; Internal Medicine of Oncology
  • Guangzhou City, China, 510180
    • Recruiting
    • Guangdong Provincial People's Hospital; Breast
  • Hangzhou City, China, 310016
    • Recruiting
    • Sir Run Run Shaw Hospital Zhejiang University
  • Hangzhou City, China, 310009
    • Recruiting
    • 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
  • Nanchang, China, 330006
    • Recruiting
    • The Second Affiliated Hospital to Nanchang University
  • Nanjing City, China, 211100
    • Recruiting
    • Jiangsu Cancer 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
  • Xi'an, China, 710061
    • Recruiting
    • First Affiliated Hospital of Medical College of Xi'an Jiaotong University
  • Zhejiang, China, 310022
    • Recruiting
    • Zhejiang Cancer Hospital
• Korea, Republic of
  • Daegu, Korea, Republic of, 41404
    • Recruiting
    • Kyungpook National University Chilgok Hospital
  • Goyang-si, Korea, Republic of, 10408
    • Recruiting
    • National Cancer Center
  • Gyeonggi-do, Korea, Republic of, 13496
    • Recruiting
    • CHA Bundang Medical Center
  • Incheon, Korea, Republic of, 22332
    • Recruiting
    • Inha University Hospital
  • Incheon, Korea, Republic of, 21431
    • Recruiting
    • Catholic Univ. of Incheon St.Mary's Hospital
  • Seoul, Korea, Republic of, 03080
    • Recruiting
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 05505
    • Recruiting
    • Asan Medical Center
  • Seoul, Korea, Republic of, 06351
    • Recruiting
    • Samsung Medical Center
  • Seoul, Korea, Republic of, 06591
    • Recruiting
    • Seoul St Mary's Hospital
  • Seoul, Korea, Republic of, 03722
    • Recruiting
    • Severance Hospital, Yonsei University Health System
  • Seoul, Korea, Republic of, 02841
    • Recruiting
    • Korea University Anam Hospital
  • Seoul, Korea, Republic of, 06273
    • Active, not recruiting
    • Gangnam Severance Hospital
• Mexico
  • Ciudad de México, Mexico, 06700
    • Recruiting
    • ARKE Estudios Clínicos S.A. de C.V.
  • Mexico City, Mexico, 14080
    • Recruiting
    • Instituto Nacional de Cancerologia; Oncology
  • Mexico City, Mexico, 03100
    • Recruiting
    • CENEIT Oncologicos; DENTRO DE CONDOMINIO SAN FRANCISCO
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44280
      • Recruiting
      • Antiguo Hospital Civil de Guadalajara Fray Antonio Alcalde
    • Guadalajara, Jalisco, Mexico, 44670
      • Recruiting
      • Panamerican Clinical Research S.A de C.V.
    • Guadalajara, Jalisco, Mexico, 44680
      • Recruiting
      • RENATI INNOVATION S.A.P.I. de C.V
  • Mexico CITY (federal District)
    • Cdmx, Mexico CITY (federal District), Mexico, 03100
      • Recruiting
      • Health Pharma Professional Research
    • Ciudad de México, Mexico CITY (federal District), Mexico, 03100
      • Recruiting
      • OncoMed; Supportive Care
    • Ciudad de México, Mexico CITY (federal District), Mexico, 01330
      • Recruiting
      • COI Centro Oncologico Internacional Santa Fe
• Poland
  • Bydgoszcz, Poland, 85-796
    • Recruiting
    • Centrum Onkologii im. Prof. Franciszka ?ukaszczyka; Ambulatorium Chemioterapii
  • Gdynia, Poland, 81-519
    • Recruiting
    • Szpital Morski im.PCK; Oddzial Onkologii Klinicznej, Oddzial Dzienny
  • Gliwice, Poland, 44-102
    • Recruiting
    • Narodowy Instytut Onkologii Odzia? w Gliwicach; Centrum Diagnostyki i Leczenia Chorób Piersi
  • Konin, Poland, 62-500
    • Recruiting
    • Przychodnia Lekarska KOMED, Roman Karaszewski
  • Koszalin, Poland, 75-581
    • Recruiting
    • Szpital Wojewódzki im. Miko?aja Kopernika; Oddzia? Dzienny Chemioterapii
  • Kraków, Poland, 31-501
    • Recruiting
    • Szpital Uniwersytecki w Krakowie; Oddzial Kliniczny Onkologii i Poradnia Onkologiczna
  • Rzeszow, Poland, 35-021
    • Recruiting
    • MRUKMED Lekarz Beata Madej-Mruk i Partner Spolka Partnerska Oddzial nr 1 w Rzeszowie
• Spain
  • Barcelona, Spain, 08035
    • Recruiting
    • Hospital Universitari Vall d'Hebron; Oncology
  • Caceres, Spain, 10003
    • Recruiting
    • Hospital San Pedro De Alcantara; Servicio de Oncologia
  • 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, 29011
    • Recruiting
    • Hospital Regional Universitario Carlos Haya; Servicio de Oncologia
  • Murcia, Spain, 30120
    • Recruiting
    • Hospital Universitario Virgen de Arrixaca; Servicio de Oncologia
  • Sevilla, Spain, 41009
    • Recruiting
    • Hospital Universitario Virgen Macarena; Servicio de Oncologia
  • Barcelona
    • L'Hospitalet de Llobregat, Barcelona, Spain, 08908
      • Recruiting
      • ICO L'Hospitalet; Servicio de oncologia medica
  • LA Coruña
    • Santiago de Compostela, LA Coruña, Spain, 15706
      • Recruiting
      • Complejo Hospitalario Universitario de Santiago (CHUS) ; Servicio de Oncologia
  • Tenerife
    • La Laguna, Tenerife, Spain, 38320
      • Recruiting
      • Hospital Universitario de Canarias;servicio de Oncologia
• Taiwan
  • Taichung, Taiwan, 404
    • Recruiting
    • China Medical University Hospital; Surgery
  • Tainan, Taiwan, 70457
    • Recruiting
    • National Cheng Kung University Hospital
  • Taipei City, Taiwan, 11217
    • Recruiting
    • Taipei Veterans General Hospital
  • Taoyuan City, Taiwan, 333
    • Recruiting
    • Chang Gung Memorial Hosipital at Linkou
  • Xitun Dist., Taiwan, 40705
    • Recruiting
    • Veterans General Hospital - Taichung
  • Zhongzheng Dist., Taiwan, 10048
    • Recruiting
    • National Taiwan University Hospital; Oncology
• Thailand
  • Songkhla, Thailand, 90110
    • Not yet recruiting
    • Songklanagarind Hospital; Department of Oncology
• Turkey
  • Ankara, Turkey, 06520
    • Recruiting
    • Memorial Ankara Hastanesi
  • Ankara, Turkey, 06010
    • Recruiting
    • Gulhane Training and Applicaton Hospital
  • Diyarbakir, Turkey, 21280
    • Recruiting
    • Dicle University Faculty of Medicine
  • Edirne, Turkey, 22030
    • Recruiting
    • Trakya University Medical Faculty
  • Istanbul, Turkey, 34214
    • Recruiting
    • Medipol Mega Üniversite Hastanesi Göztepe
  • Istanbul, Turkey, 34890
    • Active, not recruiting
    • Marmara Uni Faculty of Medicine; Medical Oncology
  • Izmir, Turkey, 35360
    • Recruiting
    • Katip Celebi University Ataturk Training and Research Hospital; Oncology
  • Izmir, Turkey, 35100
    • Recruiting
    • Ege Uni Medical Faculty Hospital; Oncology Dept
  • Kadiköy, Turkey, 34722
    • Recruiting
    • Goztepe Prof.Dr. Suleyman Yalcin City Hospital; Clinical Oncology
  • Sihhiye/Ankara, Turkey, 06230
    • Recruiting
    • Hacettepe Uni Medical Faculty Hospital; Oncology Dept
• United Kingdom
  • Basingstoke, United Kingdom, RG24 9NA
    • Recruiting
    • Basingstoke and North Hampshire Hospital
  • Blackpool, United Kingdom, FY3 8NR
    • Recruiting
    • Blackpool Victoria Hospital
  • Dumfries, United Kingdom, DG2 8RX
    • Recruiting
    • Dumfries and Galloway Royal Infirmary
  • Edinburgh, United Kingdom, EH4 2XU
    • Recruiting
    • Western General Hospital; Clinical Oncology
  • Harlow, United Kingdom, CM20 1QX
    • Recruiting
    • Princess Alexandra Hospital
  • London, United Kingdom, EC1M 6BQ
    • Recruiting
    • St Bartholomew's Hospital
  • Maidstone, United Kingdom, ME16 9QQ
    • Recruiting
    • Maidstone & Tonbridge Wells Hospital; Kent Oncology Center
  • Northwood, United Kingdom, HA6 2RN
    • Recruiting
    • Mount Vernon & Watford Trust Hospital; Dept. of Clinical Oncology
  • Oxford, United Kingdom, OX3 7LE
    • Recruiting
    • Churchill Hospital; Department of Oncology
  • Preston, United Kingdom, PR2 9HT
    • Recruiting
    • Royal Preston Hosptial
  • Winchester, United Kingdom, SO22 5DG
    • Recruiting
    • ROYAL HAMPSHIRE COUNTY HOSPITAL; R&D Office
• United States
  • California
    • Greenbrae, California, United States, 94904
      • Recruiting
      • Marin Cancer Care Inc
    • Los Alamitos, California, United States, 90720
      • Recruiting
      • Cancer Blood and Specialty Clinic
    • Los Angeles, California, United States, 90017-4803
      • Recruiting
      • Los Angeles Cancer Network
    • Orange, California, United States, 92868
      • Recruiting
      • University of California, Irvine Medical Center
    • Sacramento, California, United States, 95817
      • Recruiting
      • UC Davis Comprehensive Cancer Center
  • Colorado
    • Denver, Colorado, United States, 80220
      • Recruiting
      • Rocky Mountain Cancer Centers
    • Greeley, Colorado, United States, 85234
      • Recruiting
      • Banner MD Anderson Cancer Center
  • Connecticut
    • Norwich, Connecticut, United States, 06360-2740
      • Recruiting
      • Eastern CT Hematology and Oncology Associates
  • Florida
    • Rockledge, Florida, United States, 32955
      • Recruiting
      • Cancer Care Centers of Brevard
    • Weston, Florida, United States, 33331
      • Recruiting
      • Cleveland Clinic Florida
  • Georgia
    • Atlanta, Georgia, United States, 30303
      • Recruiting
      • Grady Health System
    • Atlanta, Georgia, United States, 30322
      • Recruiting
      • Emory University Hospital
    • Atlanta, Georgia, United States, 30342
      • Recruiting
      • Winship Cancer Institute at Emory Saint Joseph's Hospital
    • Atlanta, Georgia, United States, 30318
      • Recruiting
      • Midtown West Medical
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Recruiting
      • Karmanos Cancer Institute.
    • Grand Rapids, Michigan, United States, 49503
      • Recruiting
      • Cancer & Hematology Centers of Western Michigan
  • Minnesota
    • Saint Paul, Minnesota, United States, 55102
      • Recruiting
      • Minnesota Oncology Hematology
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Recruiting
      • Novant Health Presbyterain Medical Center
    • Winston-Salem, North Carolina, United States, 27103
      • Recruiting
      • Novant Health Forsyth Medical Center
  • Ohio
    • Canton, Ohio, United States, 44718
      • Recruiting
      • Gabrail Cancer Center
  • Oregon
    • Medford, Oregon, United States, 97504-8332
      • Recruiting
      • Asante Rogue Regional Medical Center
  • Pennsylvania
    • Broomall, Pennsylvania, United States, 19008
      • Withdrawn
      • Consultants in Medical Oncology and Hematology
    • West Chester, Pennsylvania, United States, 19380
      • Recruiting
      • Abramson Cancer Center Chester County Hospital; Hematology, Medical Oncology
    • York, Pennsylvania, United States, 17403
      • Recruiting
      • WellSpan Oncology Research
  • Texas
    • Amarillo, Texas, United States, 79106
      • Recruiting
      • Texas Oncology West
    • Dallas, Texas, United States, 75231
      • Recruiting
      • Texas Oncology - Dallas Presbyterian Hospital
    • El Paso, Texas, United States, 79905
      • Recruiting
      • Texas Tech University Health Sciences Center; Department of Internal Medicine
    • Flower Mound, Texas, United States, 75028
      • Recruiting
      • Texas Oncology (Flower Mound) - USOR
    • Fort Worth, Texas, United States, 76104
      • Recruiting
      • The Center for Cancer and Blood Disorders - Fort Worth
    • Kingwood, Texas, United States, 77339
      • Recruiting
      • Lumi Research
    • McKinney, Texas, United States, 75071
      • Recruiting
      • Texas Oncology McKinney
  • Washington
    • Kennewick, Washington, United States, 99336-7774
      • Recruiting
      • Kadlec Clinic Hematology and Oncology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• If pre/perimenopausal women and men treatment with luteinizing hormone-releasing hormone (LHRH) agonist therapy beginning at least 2 weeks prior to Day 1 of Cycle 1
• Histologically or cytologically confirmed adenocarcinoma of the breast that is locally advanced or metastatic and is not amenable to surgical or radiation therapy with curative intent
• Documented HR +/ HER2- tumor according to American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines
• Confirmation of biomarker eligibility: detection of specified mutation(s) of PIK3CA via specified test
• Disease progression after or during treatment with a combination of CDK4/6i and endocrine therapy: <= 2 prior lines of systemic therapy in mBC setting; CDK4/6i based therapy does not need to be the last one received prior study entry; one line of chemotherapy in mBC setting allowed
• Measurable or evaluable disease per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)
• Participants for whom endocrine-based therapy is recommended and treatment with cytotoxic chemotherapy is not indicated at time of entry into the study, as per national or local treatment guidelines
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2
• Life expectancy of > 6 months
• Adequate hematologic and organ function prior to initiation of study treatment

Exclusion Criteria:

• Metaplastic breast cancer
• Prior treatment in 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
• Participant who relapsed with documented evidence of progression > 12 months from completion of adjuvant CDK4/6i based therapy with no treatment for metastatic disease
• Pregnant, lactating, or breastfeeding, or intending to become pregnant during the study or at least 60 days after the final dose of study treatment
• Type 2 diabetes requiring ongoing systemic treatment at the time of study entry; or any history of Type 1 diabetes
• Inability or unwillingness to swallow pills
• Malabsorption syndrome or other condition that would interfere with enteral absorption
• Any history of leptomeningeal disease or carcinomatous meningitis
• Known and untreated, or active central nervous system (CNS) metastases. Participants with a history of treated CNS metastases are eligible if they meet specific certain criteria
• Known active, systemic infection at study enrollment, or any major episode of infection requiring treatment with intravenous antibiotics or hospitalization 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
• Requirement for daily supplemental oxygen
• Symptomatic active lung disease, including pneumonitis
• History of or active inflammatory bowel disease
• Any active bowel inflammation
• Clinically significant and active liver disease, including severe liver impairment, viral or other hepatitis, current alcohol abuse, or cirrhosis
• Participants with known human immunodeficiency virus infection that meet specific criteria
• Investigational drug(s) within 4 weeks before randomization or within 5 half-lives of the investigational drug(s), whichever is longer
• History of other malignancy within 5 years prior to screening, except for cancers with very low risk of recurrence
• Chronic therapy of >= 10 mg of prednisone per day or an equivalent dose of other anti-inflammatory corticosteroids or immunosuppressants for a chronic disease
• Allergy or hypersensitivity to components or excipients of the inavolisib, fulvestrant, or alpelisib formulations
• History of severe cutaneous reactions like Stevens-Johnson Syndrome, Erythema Multiforme, Toxic Epidermal Necrolysis, or Drug Reaction with Eosinphilia and Systemic Symptoms
• Active ongoing osteonecrosis of the jaw

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Inavolisib + Fulvestrant; Participants will be administered the treatments as outlined in the interventions section.	Drug: Inavolisib; Participants will be administered a 9 milligram (mg) inavolisib tablet orally once a day (PO QD) on Days 1-28 of each 28-day cycle.; Drug: Fulvestrant; Participants will be administered 500 mg of fulvestrant on Days 1 and 15 of Cycle 1 and then on Day 1 of each subsequent 28-day cycle.
Active Comparator: Alpelisib + Fulvestrant; Participants will be administered the treatments as outlined in the interventions section.	Drug: Fulvestrant; Participants will be administered 500 mg of fulvestrant on Days 1 and 15 of Cycle 1 and then on Day 1 of each subsequent 28-day cycle.; Drug: Alpelisib; Alpelisib will be administered to participants at the approved dose in combination with fulvestrant: 300 mg taken PO QD and on days 1-28 of each 28-day cycle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Blinded Independent Central Review (BICR)-Assessed Progression Free Survival (PFS)	From randomization until disease progression or death due to any cause (up to approximately 64 months)

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall survival (OS)	From randomization until death due to any cause (up to approximately 85 months)
BICR-Assessed Overall Response Rate (ORR)	Up to approximately 64 months
BICR-Assessed Best Overall Response (BOR)	Up to approximately 64 months
BICR-Assessed Clinical Benefit Rate (CBR)	Up to approximately 64 months
BICR-Assessed Duration of Response (DOR)	From CR or PR until disease progression or death due to any cause (up to approximately 64 months)
Time to Confirmed Deterioration (TTCD) in Pain	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 (up to approximately 85 months). Each cycle is 28 days.
TTCD in Physical Functioning	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 (up to approximately 85 months). Each cycle is 28 days.
TTCD in Role Functioning	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 (up to approximately 85 months). Each cycle is 28 days.
TTCD in Global Health Status/Quality of Life (QOL)	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 (up to approximately 85 months). Each cycle is 28 days.
Percentage of Participants with Adverse Events	Day 1 until 30 days after the final dose of study treatment (up to approximately 85 months)
Plasma Concentration of Inavolisib at Specified Timepoints	Day 1 and 15 of Cycle 1, and Day 1 of Cycles 2 and 3. Each cycle is 28 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): June 7, 2023
• Primary Completion (Estimated): March 30, 2029
• Study Completion (Estimated): March 30, 2029

Study Registration Dates

• First Submitted: December 2, 2022
• First Submitted That Met QC Criteria: December 2, 2022
• First Posted (Actual): December 12, 2022

Study Record Updates

• Last Update Posted (Actual): March 28, 2024
• Last Update Submitted That Met QC Criteria: March 27, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Hormone Antagonists; Estrogen Antagonists; Estrogen Receptor Antagonists; Phosphoinositide-3 Kinase Inhibitors; Fulvestrant; Inavolisib
• Other Study ID Numbers: WO43919; 2022-502322-41-00 (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/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

Drug and device information, study documents

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