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
2 other identifiers
interventional
420
18 countries
144
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3 breast-cancer
Started Jun 2023
144 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
December 2, 2022
CompletedFirst Posted
Study publicly available on registry
December 12, 2022
CompletedStudy Start
First participant enrolled
June 7, 2023
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 13, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
March 30, 2029
May 6, 2026
May 1, 2026
3.4 years
December 2, 2022
May 5, 2026
Conditions
Outcome Measures
Primary Outcomes (10)
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 Outcomes (12)
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)
- +7 more secondary outcomes
Study Arms (3)
Inavolisib + Fulvestrant
EXPERIMENTALParticipants will be administered the treatments as outlined in the interventions section.
Alpelisib + Fulvestrant
ACTIVE COMPARATORParticipants will be administered the treatments as outlined in the interventions section.
Sub-study: Inavolisib + Fulvestrant + CYP substrates
EXPERIMENTALParticipants will be administered the treatments as outlined in the interventions section.
Interventions
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.
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.
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.
Participants will be administered bupropion PO on Day -3 and Day 12 of Cycle 1 of the sub-study.
Participants will be administered omerprazole PO on Day -4 and Day 11 of Cycle 1 of sub-study.
Participants will be administered midazolam PO on Day -4 and Day 11 of Cycle 1 of sub-study.
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
- +15 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (144)
Cancer Blood and Specialty Clinic
Los Alamitos, California, 90720, United States
Los Angeles Cancer Network
Los Angeles, California, 90017-4803, United States
UC Davis Comprehensive Cancer Center
Sacramento, California, 95817, United States
Rocky Mountain Cancer Centers
Denver, Colorado, 80220, United States
Cleveland Clinic Florida
Weston, Florida, 33331, United States
Grady Health System
Atlanta, Georgia, 30303, United States
Midtown West Medical
Atlanta, Georgia, 30318, United States
Emory University Hospital
Atlanta, Georgia, 30322, United States
Winship Cancer Institute at Emory Saint Joseph's Hospital
Atlanta, Georgia, 30342, United States
Massachusetts General Hospital
Boston, Massachusetts, 02114, United States
Cancer & Hematology Centers of Western Michigan
Grand Rapids, Michigan, 49503, United States
Minnesota Oncology Hematology
Saint Paul, Minnesota, 55102, United States
Asante Rogue Regional Medical Center
Medford, Oregon, 97504-8332, United States
Texas Oncology - Dallas Presbyterian Hospital
Dallas, Texas, 75231, United States
Centro de Investigaciones Médicas y Desarrollo LC S.R.L
Buenos Aires, C1113AAE, Argentina
Centro Oncologico Korben
Ciudad Autonoma Buenos Aires, C1426AGE, Argentina
Fundacion CORI para la Investigacion y Prevencion del Cancer
La Rioja, F5300COE, Argentina
Instituto de Oncología de Rosario
Rosario, S2000KZE, Argentina
Hosp Provincial D. Centenarios
Rosario, S2002KDS, Argentina
CER San Juan Centro Polivalente de Asistencia e Investigacion Clinica
San Juan, J5400DIL, Argentina
Clinica Viedma S.A.
Viedma, R8500ACE, Argentina
Coffs Harbour Health Campus
Coffs Harbour, New South Wales, 2450, Australia
Concord Repatriation General Hospital
Concord, New South Wales, 2139, Australia
Kinghorn Cancer Centre
Darlinghurst, New South Wales, 2010, Australia
Gosford Hospital
Gosford, New South Wales, 2250, Australia
Icon Cancer Care Wesley
Auchenflower, Queensland, 4066, Australia
Bendigo Cancer Centre
Bendigo, Victoria, 3550, Australia
Sir Charles Gairdner Hospital
Perth, Western Australia, 6009, Australia
Cliniques Universitaires St-Luc
Brussels, 1200, Belgium
GHdC Site Les Viviers
Charleroi, 6000, Belgium
UZ Antwerpen
Edegem, 2650, Belgium
UZ Gent
Ghent, 9000, Belgium
UZ Leuven Gasthuisberg
Leuven, 3000, Belgium
Clinique Ste-Elisabeth
Namur, 5000, Belgium
NUPEC
Belo Horizonte, Minas Gerais, 30210-090, Brazil
Hospital Santa Cruz / Centro de Oncologia D'Or
Curitiba, Paraná, 80420-090, Brazil
Hospital do Cancer de Pernambuco - HCP
Recife, Pernambuco, 50040-000, Brazil
Instituto D?Or de Pesquisa e Ensino ? Hospital Esperança Recife
Recife, Pernambuco, Brazil
Liga Norte Riograndense Contra O Câncer
Natal, Rio Grande do Norte, 59040150, Brazil
Santa Casa de Misericordia de Porto Alegre
Porto Alegre, Rio Grande do Sul, 90050-170, Brazil
Hospital de Base de Sao Jose do Rio Preto
São José do Rio Preto, São Paulo, 15090-000, Brazil
Hospital Sírio-Libanês
São Paulo, São Paulo, 01308-050, Brazil
Arthur J.E. Child Comprehensive Cancer Center-Calgary
Calgary, Alberta, T2N 5G2, Canada
Cross Cancer Institute
Edmonton, Alberta, T6G 1Z2, Canada
BC Cancer ? Vancouver
Vancouver, British Columbia, V5Z 4E6, Canada
The Moncton Hospital
Moncton, New Brunswick, E1C 6Z8, Canada
Juravinski Hospital
Hamilton, Ontario, L8V 5C2, Canada
The Ottawa Hospital - General Campus
Ottawa, Ontario, K1Y 4E9, Canada
CIUSSS de l Est de l Ile de Montreal - Hopital Maisonneuve Rosemont
Montreal, Quebec, H1T 2M4, Canada
Centre Hospitalier de l'Universite de Montreal (CHUM)
Montreal, Quebec, H2X 0C2, Canada
Jewish General Hospital
Montreal, Quebec, H3T 1E2, Canada
Hôpital du Sacré-Coeur de Montreal
Montreal, Quebec, H4J 1C5, Canada
The First Hospital of Jilin University
Changchun, 130021, China
Sichuan Provincial Cancer Hospital
Chengdu, 610041, China
Sun yat-sen University Cancer Center
Guangzhou, 510060, China
Guangdong Provincial People's Hospital
Guangzhou, 510180, China
The Second Affiliated Hospital of Zhejiang University School of Medicine
Hangzhou, 310009, China
Sir Run Run Shaw Hospital Zhejiang University
Hangzhou, 310016, China
Harbin Medical University Tumor Hospital
Harbin, 150049, China
The Second Affiliated Hospital to Nanchang University
Nanchang, 330006, China
Jiangsu Cancer Hospital
Nanjing, 211100, China
Tianjin Cancer Hospital
Tianjin, 300000, China
Union Hospital Tongji Medical College Huazhong University of Science and Technology
Wuhan, 430023, China
Hubei Cancer Hospital
Wuhan, 430079, China
First Affiliated Hospital of Medical College of Xi'an Jiaotong University
Xi'an, 710061, China
Zhejiang Cancer Hospital
Zhejiang, 310022, China
Centre Hospitalier de La Cote Basque
Bayonne, 64109, France
Centre Leon Berard
Lyon, 69008, France
ICM
Montpellier, 34298, France
Centre Eugene Marquis
Rennes, 35042, France
IUCT Oncopole
Toulouse, 31100, France
Uniklinik RWTH Aachen Klinik für Gynäkologie und Geburtsmedizin
Aachen, 52074, Germany
Universitätsklinikum Essen
Essen, 45122, Germany
Praxis für Interdisziplinäre Onkologie und Hämatologie GbR
Freiburg im Breisgau, 79110, Germany
Universitätsmedizin Göttingen Georg-August-Universität
Göttingen, 37075, Germany
Mammazentrum Hamburg am Krankenhaus Jerusalem
Hamburg, 20357, Germany
Medizinische Hochschule Zentrum Frauenheilkunde Abt.Gynäkologische Onkologie
Hanover, 30625, Germany
Nationales Centrum für Tumorerkrankungen (NCT)
Heidelberg, 69120, Germany
Brustzentrum Rhein-Ruhr Servicegesellschaft mbH
Mönchengladbach, 41061, Germany
St. Vincenz-Krankenhaus GmbH Paderborn Frauen- und Kinderklinik St. Louise
Paderborn, 33098, Germany
A.O. S. Anna e San Sebastiano
Caserta, Campania, 81100, Italy
IRST Istituto Scientifico Romagnolo Per Lo Studio E Cura Dei Tumori, Sede Meldola
Meldola, Emilia-Romagna, 47014, Italy
Ospedale San Raffaele
Milan, Lombardy, 20132, Italy
Ospedale Santa Chiara
Trento, Trentino-Alto Adige, 38100, Italy
Panamerican Clinical Research S.A de C.V.
Guadalajara, Jalisco, 44670, Mexico
RENATI INNOVATION S.A.P.I. de C.V
Guadalajara, Jalisco, 44680, Mexico
COI Centro Oncologico Internacional Santa Fe
Mexico City, Mexico CITY (federal District), 01330, Mexico
Health Pharma Professional Research
Mexico City, Mexico CITY (federal District), 03100, Mexico
OncoMed
Mexico City, Mexico CITY (federal District), 03100, Mexico
ARKE Estudios Clínicos S.A. de C.V.
Mexico City, Mexico CITY (federal District), 06700, Mexico
Instituto Nacional de Cancerologia
Distrito Federal, 14080, Mexico
CENEIT Oncologicos
Mexico City, 03100, Mexico
Antiguo Hospital Civil de Guadalajara Fray Antonio Alcalde
Morelia, 58260, Mexico
Centrum Onkologii im. Prof. Franciszka ?ukaszczyka
Bydgoszcz, 85-796, Poland
Narodowy Instytut Onkologii Odzia? w Gliwicach
Gliwice, 44-102, Poland
Przychodnia Lekarska KOMED, Roman Karaszewski
Konin, 62-500, Poland
Szpital Wojewódzki im. Miko?aja Kopernika
Koszalin, 75-581, Poland
Szpital Uniwersytecki w Krakowie
Krakow, 31-501, Poland
MRUKMED Lekarz Beata Madej-Mruk i Partner Spolka Partnerska Oddzial nr 1 w Rzeszowie
Rzeszów, 35-021, Poland
Narodowy Instytut Onkologii im. M.Sklodowskiej-Curie
Warsaw, 02-781, Poland
Medical Oncology Centre of Rosebank
Johannesburg, 2196, South Africa
Richards Bay Oncology Centre
KwaZulu Natal, 3900, South Africa
Kyungpook National University Chilgok Hospital
Daegu, 41404, South Korea
National Cancer Center
Goyang-si, 10408, South Korea
Korea University Anam Hospital
Seoul, 02841, South Korea
Seoul National University Hospital
Seoul, 03080, South Korea
Severance Hospital, Yonsei University Health System
Seoul, 03722, South Korea
Asan Medical Center
Seoul, 05505, South Korea
Gangnam Severance Hospital
Seoul, 06273, South Korea
Samsung Medical Center
Seoul, 06351, South Korea
Seoul St Mary's Hospital
Seoul, 06591, South Korea
ICO L'Hospitalet
L'Hospitalet de Llobregat, Barcelona, 08908, Spain
Hospital Universitario de Canarias
San Cristóbal de La Laguna, Tenerife, 38320, Spain
Hospital San Pedro De Alcantara
Cáceres, 10003, Spain
Hospital General Universitario Gregorio Marañon
Madrid, 28007, Spain
Hospital Ramon y Cajal
Madrid, 28034, Spain
Hospital Universitario 12 de Octubre
Madrid, 28041, Spain
Hospital Regional Universitario Carlos Haya
Málaga, 29011, Spain
Hospital Universitario Virgen Macarena
Seville, 41009, Spain
China Medical University Hospital
Taichung, 404, Taiwan
National Cheng Kung University Hospital
Tainan, 70457, Taiwan
Taipei Veterans General Hospital
Taipei, 11217, Taiwan
Chang Gung Memorial Hosipital at Linkou
Taoyuan City, 333, Taiwan
Veterans General Hospital - Taichung
Xitun Dist., 40705, Taiwan
National Taiwan University Hospital
Zhongzheng Dist., 10048, Taiwan
Gulhane Training and Applicaton Hospital
Ankara, 06010, Turkey (Türkiye)
Memorial Ankara Hastanesi
Ankara, 06520, Turkey (Türkiye)
Dicle University Faculty of Medicine
Diyarbakır, 21280, Turkey (Türkiye)
Trakya University Medical Faculty
Edirne, 22030, Turkey (Türkiye)
Medipol Mega Üniversite Hastanesi Göztepe
Istanbul, 34214, Turkey (Türkiye)
Marmara Uni Faculty of Medicine
Istanbul, 34890, Turkey (Türkiye)
Ege Uni Medical Faculty Hospital
Izmir, 35100, Turkey (Türkiye)
Izmir Ataturk Training and Research Hospital
Izmir, 35360, Turkey (Türkiye)
Goztepe Prof.Dr. Suleyman Yalcin City Hospital
Kadiköy, 34722, Turkey (Türkiye)
Hacettepe Uni Medical Faculty Hospital
Sihhiye/Ankara, 06230, Turkey (Türkiye)
Basingstoke and North Hampshire Hospital
Basingstoke, RG24 9NA, United Kingdom
Blackpool Victoria Hospital
Blackpool, FY3 8NR, United Kingdom
Western General Hospital
Edinburgh, EH4 2XU, United Kingdom
Princess Alexandra Hospital
Harlow, CM20 1QX, United Kingdom
St Bartholomew's Hospital
London, EC1M 6BQ, United Kingdom
Maidstone & Tonbridge Wells Hospital
Maidstone, ME16 9QQ, United Kingdom
Mount Vernon & Watford Hospital Trust
Northwood, HA6 2RN, United Kingdom
Churchill Hospital
Oxford, OX3 7LE, United Kingdom
Royal Hampshire County Hospital
Winchester, SO22 5DG, United Kingdom
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Clinical Trials
Hoffmann-La Roche
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
December 2, 2022
First Posted
December 12, 2022
Study Start
June 7, 2023
Primary Completion (Estimated)
November 13, 2026
Study Completion (Estimated)
March 30, 2029
Last Updated
May 6, 2026
Record last verified: 2026-05
Data Sharing
- IPD Sharing
- Will share
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