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: Active, not recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Alpelisib; Drug: Inavolisib; Drug: Fulvestrant; Drug: Bupropion; Drug: Omeprazole; Drug: Midazolam

Detailed Description

The drug-drug interaction (DDI) substudy will evaluate the impact of repeat doses of inavolisib (coadministered with fulvestrant) on single-dose pharmacokinetics of sensitive CYP450 enzyme substrates (midazolam, omeprazole and bupropion) in participants with hormone receptor (HR)-positive, HER2-negative, PIK3CA-mutated, locally advanced (LA) or metastatic breast cancer (mBC), who progressed during or after CDK4/6 inhibitor (CDK4/6i) in combination with endocrine therapy (ET).

• Study Type: Interventional
• Enrollment (Estimated): 420
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1113AAE
    • Centro de Investigaciones Médicas y Desarrollo LC S.R.L
  • Ciudad Autonoma Buenos Aires, Argentina, C1426AGE
    • Centro Oncológico Korben
  • La Rioja, Argentina, F5300COE
    • Fundación CORI para la Investigación y Prevención del Cáncer
  • Rosario, Argentina, S2000KZE
    • Instituto de Oncología de Rosario
  • Rosario, Argentina, S2002KDS
    • Hosp Provincial D. Centenarios
  • San Juan, Argentina, J5400DIL
    • CER San Juan Centro Polivalente de Asistencia e Investigacion Clinica
  • Viedma, Argentina, R8500ACE
    • Clinica Viedma S.A.
• Australia
  • New South Wales
    • Coffs Harbour, New South Wales, Australia, 2450
      • Coffs Harbour Health Campus
    • Concord, New South Wales, Australia, 2139
      • Concord Repatriation General Hospital
    • Darlinghurst, New South Wales, Australia, 2010
      • Kinghorn Cancer Centre
    • Gosford, New South Wales, Australia, 2250
      • Gosford Hospital
  • Queensland
    • Auchenflower, Queensland, Australia, 4066
      • Icon Cancer Care Wesley
  • Victoria
    • Bendigo, Victoria, Australia, 3550
      • Bendigo Cancer Centre
  • Western Australia
    • Perth, Western Australia, Australia, 6009
      • Sir Charles Gairdner Hospital
• Belgium
  • Brussels, Belgium, 1200
    • Cliniques Universitaires St-Luc
  • Charleroi, Belgium, 6000
    • GHdC Site Les Viviers
  • Edegem, Belgium, 2650
    • UZ Antwerpen
  • Ghent, Belgium, 9000
    • UZ Gent
  • Leuven, Belgium, 3000
    • UZ Leuven Gasthuisberg
  • Namur, Belgium, 5000
    • Clinique Ste-Elisabeth
• Brazil
  • Minas Gerais
    • Belo Horizonte, Minas Gerais, Brazil, 30210-090
      • NUPEC
  • Paraná
    • Curitiba, Paraná, Brazil, 80420-090
      • Hospital Santa Cruz / Centro de Oncologia D'Or
  • Pernambuco
    • Recife, Pernambuco, Brazil, 50040-000
      • Hospital do Cancer de Pernambuco - HCP
    • Recife, Pernambuco, Brazil
      • Instituto D?Or de Pesquisa e Ensino ? Hospital Esperança Recife
  • Rio Grande do Norte
    • Natal, Rio Grande do Norte, Brazil, 59040150
      • Liga Norte Riograndense Contra O Cancer
  • Rio Grande do Sul
    • Porto Alegre, Rio Grande do Sul, Brazil, 90050-170
      • Santa Casa de Misericordia de Porto Alegre
  • São Paulo
    • São José do Rio Preto, São Paulo, Brazil, 15090-000
      • Hospital de Base de Sao Jose do Rio Preto
    • São Paulo, São Paulo, Brazil, 01308-050
      • Hospital Sírio-Libanês
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 5G2
      • Arthur J.E. Child Comprehensive Cancer Center-Calgary
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Cross Cancer Institute
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 4E6
      • BC Cancer ? Vancouver
  • New Brunswick
    • Moncton, New Brunswick, Canada, E1C 6Z8
      • The Moncton Hospital
  • Ontario
    • Hamilton, Ontario, Canada, L8V 5C2
      • Juravinski Hospital
    • Ottawa, Ontario, Canada, K1Y 4E9
      • The Ottawa Hospital - General Campus
  • Quebec
    • Montreal, Quebec, Canada, H3T 1E2
      • Jewish General Hospital
    • Montreal, Quebec, Canada, H4J 1C5
      • Hopital du Sacre-Coeur de Montreal
    • Montreal, Quebec, Canada, H2X 0C2
      • Centre Hospitalier de l'Universite de Montreal (CHUM)
    • Montreal, Quebec, Canada, H1T 2M4
      • CIUSSS de l Est de l Ile de Montreal - Hopital Maisonneuve Rosemont
• China
  • Changchun, China, 130021
    • The First Hospital of Jilin University
  • Chengdu, China, 610041
    • Sichuan Provincial Cancer Hospital
  • Guangzhou, China, 510060
    • Sun Yat-sen University Cancer Center
  • Guangzhou, China, 510180
    • Guangdong Provincial People's Hospital
  • Hangzhou, China, 310009
    • The Second Affiliated Hospital of Zhejiang University School of Medicine
  • Hangzhou, China, 310016
    • Sir Run Run Shaw Hospital Zhejiang University
  • Harbin, China, 150049
    • Harbin Medical University Tumor Hospital
  • Nanchang, China, 330006
    • The Second Affiliated Hospital to Nanchang University
  • Nanjing, China, 211100
    • Jiangsu Cancer Hospital
  • Tianjin, China, 300000
    • Tianjin cancer hospital
  • Wuhan, China, 430079
    • Hubei Cancer Hospital
  • Wuhan, China, 430023
    • Union Hospital Tongji Medical College Huazhong University of Science and Technology
  • Xi'an, China, 710061
    • First Affiliated Hospital of Medical College of Xi'an Jiaotong University
  • Zhejiang, China, 310022
    • Zhejiang Cancer Hospital
• France
  • Bayonne, France, 64109
    • Centre Hospitalier de la Cote Basque
  • Lyon, France, 69008
    • Centre Léon Bérard
  • Montpellier, France, 34298
    • ICM
  • Rennes, France, 35042
    • Centre Eugene Marquis
  • Toulouse, France, 31100
    • IUCT Oncopole
• Germany
  • Aachen, Germany, 52074
    • Uniklinik RWTH Aachen Klinik für Gynäkologie und Geburtsmedizin
  • Essen, Germany, 45122
    • Universitatsklinikum Essen
  • Freiburg im Breisgau, Germany, 79110
    • Praxis für Interdisziplinäre Onkologie und Hämatologie GbR
  • Göttingen, Germany, 37075
    • Universitätsmedizin Göttingen Georg-August-Universität
  • Hamburg, Germany, 20357
    • Mammazentrum Hamburg am Krankenhaus Jerusalem
  • Hanover, Germany, 30625
    • Medizinische Hochschule Zentrum Frauenheilkunde Abt.Gynäkologische Onkologie
  • Heidelberg, Germany, 69120
    • Nationales Centrum für Tumorerkrankungen (NCT)
  • Mönchengladbach, Germany, 41061
    • Brustzentrum Rhein-Ruhr Servicegesellschaft mbH
  • Paderborn, Germany, 33098
    • St. Vincenz-Krankenhaus GmbH Paderborn Frauen- und Kinderklinik St. Louise
• Italy
  • Campania
    • Caserta, Campania, Italy, 81100
      • A.O. S. Anna e San Sebastiano
  • Emilia-Romagna
    • Meldola, Emilia-Romagna, Italy, 47014
      • IRST Istituto Scientifico Romagnolo Per Lo Studio E Cura Dei Tumori, Sede Meldola
  • Lombardy
    • Milan, Lombardy, Italy, 20132
      • Ospedale San Raffaele
  • Trentino-Alto Adige
    • Trento, Trentino-Alto Adige, Italy, 38100
      • Ospedale Santa Chiara
• Mexico
  • Distrito Federal, Mexico, 14080
    • Instituto Nacional de Cancerologia
  • Mexico City, Mexico, 03100
    • CENEIT Oncologicos
  • Morelia, Mexico, 58260
    • Antiguo Hospital Civil de Guadalajara Fray Antonio Alcalde
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44670
      • Panamerican Clinical Research S.A de C.V.
    • Guadalajara, Jalisco, Mexico, 44680
      • RENATI INNOVATION S.A.P.I. de C.V
  • Mexico CITY (federal District)
    • Mexico City, Mexico CITY (federal District), Mexico, 06700
      • ARKE Estudios Clínicos S.A. de C.V.
    • Mexico City, Mexico CITY (federal District), Mexico, 03100
      • OncoMed
    • Mexico City, Mexico CITY (federal District), Mexico, 03100
      • Health Pharma Professional Research
    • Mexico City, Mexico CITY (federal District), Mexico, 01330
      • COI Centro Oncologico Internacional Santa Fe
• Poland
  • Bydgoszcz, Poland, 85-796
    • Centrum Onkologii im. Prof. Franciszka ?ukaszczyka
  • Gliwice, Poland, 44-102
    • Narodowy Instytut Onkologii Odzia? w Gliwicach
  • Konin, Poland, 62-500
    • Przychodnia Lekarska KOMED, Roman Karaszewski
  • Koszalin, Poland, 75-581
    • Szpital Wojewódzki im. Miko?aja Kopernika
  • Krakow, Poland, 31-501
    • Szpital Uniwersytecki w Krakowie
  • Rzeszów, Poland, 35-021
    • MRUKMED Lekarz Beata Madej-Mruk i Partner Spolka Partnerska Oddzial nr 1 w Rzeszowie
  • Warsaw, Poland, 02-781
    • Narodowy Instytut Onkologii im. M.Sklodowskiej-Curie
• South Africa
  • Johannesburg, South Africa, 2196
    • Medical Oncology Centre of Rosebank
  • KwaZulu Natal, South Africa, 3900
    • Richards Bay Oncology Centre
• South Korea
  • Daegu, South Korea, 41404
    • Kyungpook National University Chilgok Hospital
  • Goyang-si, South Korea, 10408
    • National Cancer Center
  • Seoul, South Korea, 03080
    • Seoul National University Hospital
  • Seoul, South Korea, 05505
    • Asan Medical Center
  • Seoul, South Korea, 06351
    • Samsung Medical Center
  • Seoul, South Korea, 03722
    • Severance Hospital, Yonsei University Health System
  • Seoul, South Korea, 02841
    • Korea University Anam Hospital
  • Seoul, South Korea, 06273
    • Gangnam Severance Hospital
  • Seoul, South Korea, 06591
    • Seoul St Mary's Hospital
• Spain
  • Cáceres, Spain, 10003
    • Hospital San Pedro De Alcantara
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre
  • Madrid, Spain, 28034
    • Hospital Ramon y Cajal
  • Madrid, Spain, 28007
    • Hospital General Universitario Gregorio Marañon
  • Málaga, Spain, 29011
    • Hospital Regional Universitario Carlos Haya
  • Seville, Spain, 41009
    • Hospital Universitario Virgen Macarena
  • Barcelona
    • L'Hospitalet de Llobregat, Barcelona, Spain, 08908
      • ICO L'Hospitalet
  • Tenerife
    • San Cristóbal de La Laguna, Tenerife, Spain, 38320
      • Hospital Universitario de Canarias
• Taiwan
  • Taichung, Taiwan, 404
    • China Medical University Hospital
  • Tainan, Taiwan, 70457
    • National Cheng Kung University Hospital
  • Taipei, Taiwan, 11217
    • Taipei Veterans General Hospital
  • Taoyuan City, Taiwan, 333
    • Chang Gung Memorial Hosipital at Linkou
  • Xitun Dist., Taiwan, 40705
    • Veterans General Hospital - Taichung
  • Zhongzheng Dist., Taiwan, 10048
    • National Taiwan University Hospital
• Turkey (Türkiye)
  • Ankara, Turkey (Türkiye), 06520
    • Memorial Ankara Hastanesi
  • Ankara, Turkey (Türkiye), 06010
    • Gulhane Training and Applicaton Hospital
  • Diyarbakır, Turkey (Türkiye), 21280
    • Dicle University Faculty of Medicine
  • Edirne, Turkey (Türkiye), 22030
    • Trakya University Medical Faculty
  • Istanbul, Turkey (Türkiye), 34214
    • Medipol Mega Üniversite Hastanesi Göztepe
  • Istanbul, Turkey (Türkiye), 34890
    • Marmara Uni Faculty of Medicine
  • Izmir, Turkey (Türkiye), 35100
    • Ege Uni Medical Faculty Hospital
  • Izmir, Turkey (Türkiye), 35360
    • Izmir Ataturk Training and Research Hospital
  • Kadiköy, Turkey (Türkiye), 34722
    • Goztepe Prof.Dr. Suleyman Yalcin City Hospital
  • Sihhiye/Ankara, Turkey (Türkiye), 06230
    • Hacettepe Uni Medical Faculty Hospital
• United Kingdom
  • Basingstoke, United Kingdom, RG24 9NA
    • Basingstoke And North Hampshire Hospital
  • Blackpool, United Kingdom, FY3 8NR
    • Blackpool Victoria Hospital
  • Edinburgh, United Kingdom, EH4 2XU
    • Western General Hospital
  • Harlow, United Kingdom, CM20 1QX
    • Princess Alexandra Hospital
  • London, United Kingdom, EC1M 6BQ
    • St Bartholomew's Hospital
  • Maidstone, United Kingdom, ME16 9QQ
    • Maidstone & Tonbridge Wells Hospital
  • Northwood, United Kingdom, HA6 2RN
    • Mount Vernon & Watford Hospital Trust
  • Oxford, United Kingdom, OX3 7LE
    • Churchill Hospital
  • Winchester, United Kingdom, SO22 5DG
    • Royal Hampshire County Hospital
• United States
  • California
    • Los Alamitos, California, United States, 90720
      • Cancer Blood and Specialty Clinic
    • Los Angeles, California, United States, 90017-4803
      • Los Angeles Cancer Network
    • Sacramento, California, United States, 95817
      • UC Davis Comprehensive Cancer Center
  • Colorado
    • Denver, Colorado, United States, 80220
      • Rocky Mountain Cancer Centers
  • Florida
    • Weston, Florida, United States, 33331
      • Cleveland Clinic Florida
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University Hospital
    • Atlanta, Georgia, United States, 30303
      • Grady Health System
    • Atlanta, Georgia, United States, 30318
      • Midtown West Medical
    • Atlanta, Georgia, United States, 30342
      • Winship Cancer Institute at Emory Saint Joseph's Hospital
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Michigan
    • Grand Rapids, Michigan, United States, 49503
      • Cancer & Hematology Centers of Western Michigan
  • Minnesota
    • Saint Paul, Minnesota, United States, 55102
      • Minnesota Oncology Hematology
  • Oregon
    • Medford, Oregon, United States, 97504-8332
      • Asante Rogue Regional Medical Center
  • Texas
    • Dallas, Texas, United States, 75231
      • Texas Oncology - Dallas Presbyterian Hospital

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria for Main Study and Sub-study:

• 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 for both Main Study and Sub-study:

• 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
• 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
• 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
• 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
• Active ongoing osteonecrosis of the jaw

Exclusion Criteria for Main Study Only:

• Pregnant, lactating, or breastfeeding, or intending to become pregnant during the study or at least 60 days after the final dose of study treatment
• 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
• Investigational drug(s) within 4 weeks before randomization or within 5 half-lives of the investigational drug(s), whichever is longer
• 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

Exclusion Criteria for Sub-study Only:

• Pregnant, lactating, or breastfeeding, or intending to become pregnant during the substudy or within 2 weeks after the final dose of inavolisib and within 2 years after the final dose of fulvestrant, whichever is longer
• 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 -4 of Cycle 1
• Investigational drug(s) within 4 weeks prior to Day -4 or within 5 half-lives of the investigational drug(s), whichever is longer
• Allergy or hypersensitivity to components or excipients of the inavolisib, fulvestrant formulations
• Treatment with mild, moderate, or strong inducers of CYP2B6, CYP3A4, and/or CYP2C19 (including St. John's Wort) within 14 days or 5 drug-elimination half-lives, whichever is longer, prior to initiation of study treatment on Day -4 until after the final PK sample has been collected on Day 15 of Cycle 1
• Treatment with mild, moderate, or strong inhibitors of CYP2B6, CYP3A4, and/or CYP2C19 (including grapefruit juice or supplements) within 14 days or 5 drug-elimination half-lives, whichever is longer, prior to initiation of study treatment on Day -4 until after the final PK sample has been collected on Day 15 of Cycle 1

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

3

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 of main study and sub-study.; 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 of main study and sub-study.
Active Comparator: Alpelisib + Fulvestrant; Participants will be administered the treatments as outlined in the interventions section.	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.; 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 of main study and sub-study.
Experimental: Sub-study: Inavolisib + Fulvestrant + CYP substrates; 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 of main study and sub-study.; 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 of main study and sub-study.; Drug: Bupropion; Participants will be administered bupropion PO on Day -3 and Day 12 of Cycle 1 of the sub-study.; Drug: Omeprazole; Participants will be administered omerprazole PO on Day -4 and Day 11 of Cycle 1 of sub-study.; Drug: Midazolam; Participants will be administered midazolam PO on Day -4 and Day 11 of Cycle 1 of sub-study.

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)
Sub-study: Maximum observed Drug Concentration (Cmax) for Midazolam	Day -4 and -3 of Cycle (C) 1, Day (D) 11 and C1D12. A cycle is 28 days.
Sub-study: Cmax for Bupropion	Day -3, -2, -1 of C1D1, C1D12, C1D13, C1D14 and C1D15. A cycle is 28 days.
Sub-study: Cmax for Omeprazole	Day -4 and -3 of C1D11 and C1D12. A cycle is 28 days.
Sub-study: Area Under the Concentration-Time Curve From Time 0 to Last Measurable Concentration (AUC [0-last]) for Midazolam	Day -4 and -3 of C1D11 and C1D12. A cycle is 28 days.
Sub-study: AUC (0-last) for Bupropion	Day -3, -2, -1 of C1D1, C1D12, C1D13, C1D14 and C1D15. A cycle is 28 days.
Sub-study: AUC (0-last) for Omeprazole	Day -4 and -3 of C1D11 and C1D12. A cycle is 28 days.
Sub-study: Area Under the Concentration-Time Curve From Time 0 to Infinity (AUC [0-infinity]) for Midazolam	Day -4 and -3 of C1D11 and C1D12. A cycle is 28 days.
Sub-study: AUC (0-infinity) for Bupropion	Day -3, -2, -1 of C1D1, C1D12, C1D13, C1D14 and C1D15. A cycle is 28 days.
Sub-study: AUC (0-infinity) for Omeprazole	Day -4 and -3 of C1D11 and C1D12. A cycle is 28 days.

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.
Sub-study: Percentage of Participants with Adverse Events	Day -4 until 30 days after the final dose of study treatment (up to approximately 85 months)

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): November 13, 2026
• 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): May 6, 2026
• Last Update Submitted That Met QC Criteria: May 5, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; 2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Polycyclic Compounds; Steroids; Fused-Ring Compounds; Benzazepines; Estradiol; Estrenes; Estranes; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Benzodiazepines; Ketones; Propiophenones; Fulvestrant; Midazolam; Omeprazole; Bupropion; inavolisib; Alpelisib
• 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: For eligible studies, qualified researchers may request access to individual patient level clinical data. See Roche's commitment to transparency of clinical study information here: https://go.roche.com/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