A Study Evaluating the Efficacy and Safety of Inavolisib + Palbociclib + Fulvestrant vs Placebo + Palbociclib + Fulvestrant in Participants With PIK3CA-Mutant, Hormone Receptor-Positive, HER2-Negative, Locally Advanced or Metastatic Breast Cancer (INAVO120)

A Phase III, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Efficacy and Safety of Inavolisib Plus Palbociclib and Fulvestrant Versus Placebo Plus Palbociclib and Fulvestrant in Patients With PIK3CA-Mutant, Hormone Receptor-Positive, HER2-Negative, Locally Advanced or Metastatic Breast Cancer

This study will evaluate the efficacy, safety, and pharmacokinetics of inavolisib in combination with palbociclib and fulvestrant compared with placebo plus palbociclib and fulvestrant in participants with PIK3CA-mutant, hormone receptor (HR)-positive, HER2-negative locally advanced or metastatic breast cancer whose disease progressed during treatment or within 12 months of completing adjuvant endocrine therapy and who have not received prior systemic therapy for metastatic disease.

Study Overview

• Status: Active, not recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Inavolisib; Drug: Palbociclib; Drug: Fulvestrant; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 325
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Ciudad Autonoma Buenos Aires, Argentina, C1426AGE
    • Centro Oncológico Korben
  • Rosario, Argentina, S2002KDS
    • Hosp Provincial D. Centenarios
  • Ciudad Autónoma de BuenosAires
    • Buenos Aires, Ciudad Autónoma de BuenosAires, Argentina, C1113AAE
      • Centro de Investigaciones Médicas y Desarrollo LC S.R.L
• Australia
  • New South Wales
    • Macquarie Park, New South Wales, Australia, 2109
      • Macquarie University Hospital
    • Wollongong, New South Wales, Australia, 2500
      • Southern Medical Day Care Centre
  • Queensland
    • South Brisbane, Queensland, Australia, 4101
      • Mater Adult Hospital
    • Woolloongabba, Queensland, Australia, 4102
      • Princess Alexandra Hospital
  • Victoria
    • Fitzroy, Victoria, Australia, 3065
      • Western Health
    • Frankston, Victoria, Australia, 3199
      • Peninsula and South Eastern Haematology and Oncology Group
• Belgium
  • Leuven, Belgium, 3000
    • UZ Leuven Gasthuisberg
• Brazil
  • Rio Grande do Sul
    • Porto Alegre, Rio Grande do Sul, Brazil, 90050-170
      • Santa Casa de Misericordia de Porto Alegre
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 5G2
      • Arthur J.E. Child Comprehensive Cancer Center-Calgary
  • Ontario
    • London, Ontario, Canada, N6A 4L6
      • London Regional Cancer Program, London Health Sciences Centre, Baines Centre
    • Ottawa, Ontario, Canada, K1H 8L6
      • Ottawa Hospital
    • Toronto, Ontario, Canada, M5G 1Z5
      • Princess Margaret Cancer Center
  • Quebec
    • Québec, Quebec, Canada, G1S 4L8
      • Hopital du Saint Sacrement
• China
  • Beijing, China, 100142
    • Beijing Cancer Hospital
  • Changchun, China, 130021
    • The First Hospital of Jilin University
  • Chongqing, China, 400016
    • The First Affiliated Hospital, Chongqing Medical University
  • Fujian, China, 350001
    • Fujian Medical University Union Hospital
  • Guangzhou, China, 510060
    • Sun Yet-sen University Cancer Center
  • Hangzhou, China, 310022
    • Zhejiang Cancer Hospital
  • Harbin, China, 150081
    • Harbin Medical University Cancer Hospital
  • Shanghai, China, 201315
    • Fudan University Shanghai Cancer Center
  • Shijiazhuang, China, 050035
    • Hebei Medical University Fourth Hospital
  • Tianjin, China, 300060
    • Tianjin cancer hospital
  • Wuhan, China, 430079
    • Hubei Cancer Hospital
  • Xi'an, China, 710061
    • First Affiliated Hospital of Medical College of Xi'an Jiaotong University
  • Zhengzhou, China, 450008
    • Henan Cancer Hospital
• Denmark
  • Vejle, Denmark, 7100
    • Vejle Sygehus
• France
  • Clermont-Ferrand, France, 63003
    • Centre Jean Perrin Centre Regional de Lutte Contre Le Cancer D auvergne
  • Dijon, France, 21079
    • Centre Georges Francois Leclerc
  • Lille, France, 59020
    • Centre Oscar Lambret
  • Lyon, France, 69373
    • Hopital Prive Jean Mermoz
  • Montpellier, France, 34298
    • Institut régional du Cancer Montpellier
  • Toulouse, France, 31059
    • Institut Universitaire du cancer de Toulouse-Oncopole
• Georgia
  • Tbilisi, Georgia, 0159
    • Tbilisi Oncology Dispensary
  • Tbilisi, Georgia, 0112
    • Israel-Georgian Medical Research Clinic Healthycore
• Germany
  • Berlin, Germany, 13581
    • Ambulantes Tumorzentrum Spandau
  • Essen, Germany, 45136
    • Klinikum Essen-Mitte Ev. Huyssens-Stiftung / Knappschafts GmbH
  • Heidelberg, Germany, 69120
    • Nationales Centrum für Tumorerkrankungen (NCT)
  • Mannheim, Germany, 68167
    • Universitätsklinikum Mannheim
  • Trier, Germany, 54290
    • Klinikum Mutterhaus der Borromaeerinnen gGmbH
  • Ulm, Germany, 89075
    • Universitätsfrauenklinik Ulm
• Greece
  • Athens, Greece, 115 22
    • Anticancer Hospital Ag. Savas
  • Heraklion, Greece, 711 10
    • Univ General Hosp Heraklion
  • Thessaloniki, Greece, 570 01
    • European Interbalkan Medical Center
  • Thessaloniki, Greece, 546 45
    • Euromedical General Clinic of Thessaloniki
• Hong Kong
  • Hong Kong, Hong Kong
    • Queen Mary Hospital
• Hungary
  • Budapest, Hungary, 1122
    • Orszagos Onkologiai Intezet
  • Budapest, Hungary, 1145
    • Uzsoki Utcai Kórház
  • Szolnok, Hungary, 5004
    • Jász-Nagykun-Szolnok Megyei Hetényi Géza Kórház-Rendelőintézet
• Italy
  • Emilia-Romagna
    • Parma, Emilia-Romagna, Italy, 43100
      • A.O. Universitaria Di Parma
  • Lombardy
    • Brescia, Lombardy, Italy, 25123
      • Az. Osp. Spedali Civili
    • Milan, Lombardy, Italy, 20133
      • Fondazione IRCCS Istituto Nazionale dei Tumori
  • Tuscany
    • Bagno a Ripoli, Tuscany, Italy, 50012
      • Ospedale Santa Maria Annunziata
  • Veneto
    • Padua, Veneto, Italy, 35128
      • IOV - Istituto Oncologico Veneto - IRCCS
• Malaysia
  • Federal Territory of Putrajaya
    • Putrajaya, Federal Territory of Putrajaya, Malaysia, 62250
      • National Cancer Institute IKN
  • Johor
    • Johor Bahru, Johor, Malaysia, 81100
      • Hospital Sultan Ismail
  • Sarawak
    • Sarawak, Sarawak, Malaysia, 93586
      • Sarawak General Hospital
• New Zealand
  • Palmerston North, New Zealand, 4442
    • Palmerston North Hospital
• Poland
  • Gliwice, Poland, 44-102
    • Narodowy Instytut Onkologii Odzia? w Gliwicach
  • Konin, Poland, 625000
    • Przychodnia Lekarska KOMED, Roman Karaszewski
  • Warsaw, Poland, 02-781
    • Narodowy Inst.Onkologii im.Sklodowskiej-Curie Panstw.Inst.Bad
• Portugal
  • Lisbon, Portugal, 1400-038
    • Centro Clinico Champalimaud
  • Porto, Portugal, 4200-072
    • IPO do Porto
• Russia
  • Volgograd, Russia, 400138
    • Volgograd Regional Clinical Oncology Dispensary
  • Yaroslavl, Russia, 150040
    • Regional Clinical Oncology Hospital
  • Moscow Oblast
    • Moscow, Moscow Oblast, Russia, 143422
      • MEDSI Clinical Hospital on Pyatnitsky Highway
    • Moscow, Moscow Oblast, Russia, 111123
      • Moscow Clinical Scientific Center
    • Moscow, Moscow Oblast, Russia, 115552
      • Blokhin Cancer Research Center
    • Moskva, Moscow Oblast, Russia, 119421
      • LLC Medscan
    • Yudino, Moscow Oblast, Russia, 143081
      • Clinical Hospital Lapino (LLC Haven)
  • Sankt-Peterburg
    • Saint Petersburg, Sankt-Peterburg, Russia, 197082
      • Medical Clinic "AB Medical group"
• Singapore
  • Singapore, Singapore, 119228
    • National University Hospital
  • Singapore, Singapore, 168583
    • National Cancer Centre
• South Korea
  • Busan, South Korea, 49241
    • Pusan National University Hospital
  • Daegu, South Korea, 41404
    • Kyungpook National University Medical Center
  • Gyeonggi-do, South Korea, 13620
    • Seoul National University Bundang Hospital
  • Gyeonggi-do, South Korea, 10408
    • National Cancer Center
  • Seoul, South Korea, 03080
    • Seoul National University Hospital
  • Seoul, South Korea, 05505
    • Asan 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, 07985
    • Ewha Womans University Mokdong Hospital
  • Seoul, South Korea, 6351
    • Samsung Medical Center
• Spain
  • Barcelona, Spain, 08003
    • Hospital del Mar
  • Barcelona, Spain, 08035
    • Vall d?Hebron Institute of Oncology (VHIO), Barcelona
  • Barcelona, Spain, 08907
    • Insituto Catalán de Oncologia (ICO)
  • Jaén, Spain, 23007
    • Complejo Hospitalario de Jaen-Hospital Universitario Medico Quirurgico
  • Madrid, Spain, 28040
    • Hospital Clinico San Carlos
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre
  • Madrid, Spain, 28007
    • Hospital General Universitario Gregorio Marañon
  • Madrid, Spain, 28222
    • Hospital Universitario Puerta de Hierro
  • Madrid, Spain, 28027
    • Clinica Universidad de Navarra-Madrid
  • Seville, Spain, 41009
    • Hospital Universitario Virgen Macarena
  • Valencia, Spain, 46010
    • Hospital Clínico Universitario de Valencia
  • Valencia, Spain, 46009
    • Instituto Valenciano Oncologia
  • Barcelona
    • Badalona, Barcelona, Spain, 08916
      • Hospital Universitari Germans Trias i Pujol
  • Navarre
    • Pamplona, Navarre, Spain, 31008
      • Clinica Universitaria de Navarra
  • Tenerife
    • San Cristóbal de La Laguna, Tenerife, Spain, 38320
      • Hospital Universitario de Canarias
• Taiwan
  • Kaohsiung City, Taiwan, 807
    • Kaohsiung Medical Uni Chung-Ho Hospital
  • Taipei, Taiwan, 114
    • Tri-Service General Hospital, Division of General Surgery
  • Taipei, Taiwan, 112
    • Koo Foundation Sun Yat-Sen Cancer Center
  • Taipei, Taiwan, 100
    • National Taiwan Uni Hospital
  • Taipei, Taiwan, 00112
    • Veterans General Hospital
• Thailand
  • Bangkok, Thailand, 10400
    • Ramathibodi Hospital
  • Chiang Mai, Thailand, 50200
    • Maharaj Nakorn Chiang Mai Hospital
  • Lak Si, Thailand, 10210
    • Chulabhorn Hospital
  • Songkhla, Thailand, 90110
    • Songklanagarind Hospital
• Turkey (Türkiye)
  • Adana, Turkey (Türkiye), 01120
    • Adana Baskent University Hospital
  • Ankara, Turkey (Türkiye), 06010
    • Gulhane Training and Research Hospital
  • Bornova, ?zm?r, Turkey (Türkiye), 35100
    • Ege University Medical Faculty
  • Istanbul, Turkey (Türkiye), 34098
    • Istanbul University Cerrahpasa Faculty of Medicine
  • Istanbul, Turkey (Türkiye), 34384
    • Prof. Dr. Cemil Tascioglu City Hospital
• Ukraine
  • Dnipropetrovsk, Ukraine, 49102
    • City Clinical Hospital #4
  • Kryvyi Rih, Ukraine, 50048
    • ME Kryviy Rih Oncology Dispensary of Dnipropetrovs?k Regional Council
  • Kyiv, Ukraine, 03115
    • Kyiv City Clinical Oncological Center
  • KIEV Governorate
    • Ivano-Frankivsk, KIEV Governorate, Ukraine, 76018
      • Municipal Institution SubCarpathian Clinical Oncological Centre
    • Uzhhorod, KIEV Governorate, Ukraine, 88000
      • Uzhhorod Central City Clinical Hospital
  • Kharkiv Governorate
    • Kharkiv, Kharkiv Governorate, Ukraine, 61018
      • SI Institute of general&urgent surgery n/a Zaytseva V.T NAMSU
• United Kingdom
  • London, United Kingdom, SW3 6JJ
    • Royal Marsden Hospital - Fulham
  • Northwood, United Kingdom, HA6 2RN
    • Mount Vernon Hospital
  • Oxford, United Kingdom, OX3 7LJ
    • Churchill Hospital
  • Plymouth, United Kingdom, PL6 8DH
    • Derriford Hospital
• United States
  • California
    • Beverly Hills, California, United States, 90211
      • Beverly Hills Cancer Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital.
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University Baptist Medical Center
  • Tennessee
    • Chattanooga, Tennessee, United States, 37403
      • Sarah Cannon Research Institute / Tennessee Oncology
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute / Tennessee Oncology
  • Texas
    • Austin, Texas, United States, 78731
      • Texas Oncology - Central South
    • El Paso, Texas, United States, 79905
      • Texas Tech University Health Sciences Center
    • Tyler, Texas, United States, 75702
      • Texas Oncology - Northeast Texas
  • Washington
    • Tacoma, Washington, United States, 98405
      • Northwest Medical Specialties

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria

• Confirmed diagnosis of HR+/HER2- breast cancer
• Metastatic or locally advanced disease not amenable to curative therapy
• Progression of disease during adjuvant endocrine treatment or within 12 months of completing adjuvant endocrine therapy with an aromatase inhibitor or tamoxifen
• Receiving LHRH agonist therapy for at least 2 weeks prior to Day 1 of Cycle 1 if pre/peri-menopausal
• Confirmation of biomarker eligibility (detection of specified mutation(s) of PIK3CA via specified test)
• Consent to provide fresh or archival tumor tissue specimen
• Measurable disease per Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1); evaluable "bone-only" disease is not eligible; "bone-only" disease with at least one measurable, soft-tissue component, even if considered disease that is limited to bone but has lytic or mixed lytic/blastic lesions and at least one measurable soft-tissue component per RECIST v1.1 may be eligible
• Eastern Cooperative Oncology Group Performance Status of 0 or 1
• Life expectancy of > 6 months
• Adequate hematologic and organ function within 14 days prior to initiation of study treatment

Exclusion Criteria

• Metaplastic breast cancer
• Any history of leptomeningeal disease or carcinomatous meningitis
• Any prior systemic therapy for metastatic breast cancer
• Prior treatment with fulvestrant or any selective estrogen-receptor degrader, with the exception of participants that have received fulvestrant or any selective estrogen-receptor degrader as part of neoadjuvant therapy only and with treatment duration of no longer than 6 months
• Prior treatment with any PI3K, AKT, or mTOR inhibitor, or any agent whose mechanism of action is to inhibit the PI3K-AKT-mTOR pathway
• Type 2 diabetes requiring ongoing systemic treatment at the time of study entry; or any history of Type 1 diabetes
• Known and untreated, or active CNS metastases. Patients with a history of treated CNS metastases may be eligible
• Active inflammatory or infectious conditions in either eye, or any eye conditions expected to require surgery during the study treatment period
• Symptomatic active lung disease, or requiring daily supplemental oxygen
• History of inflammatory bowel disease or active bowel inflammation
• Anti-cancer therapy within 2 weeks before study entry
• Investigational drug(s) within 4 weeks before randomization
• Prior radiotherapy to >= 25% of bone marrow, or hematopoietic stem cell or bone marrow transplantation
• Chronic corticosteroid therapy or immunosuppressants
• Pregnant, lactating, or breastfeeding, or intending to become pregnant during the study or within 2 weeks after the final dose of study treatment
• Major surgical procedure, or significant traumatic injury, within 28 days prior to Day 1 of Cycle 1

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Inavolisib + Palbociclib + Fulvestrant; Participants will receive inavolisib, palbociclib, and fulvestrant.	Drug: Inavolisib; Participants will receive oral inavolisib on Days 1-28 of each 28-day cycle.; Other Names: GDC-0077; Drug: Palbociclib; Participants will receive oral palbociclib on Days 1-21 of each 28-day cycle.; Drug: Fulvestrant; Participants will receive intramuscular (IM) fulvestrant approximately every 4 weeks.
Placebo Comparator: Placebo + Palbociclib + Fulvestrant; Participants will receive placebo, palbociclib, and fulvestrant. Participants randomized to the placebo arm who are still deriving benefit from the study treatment will be given an optional opportunity to crossover to the inavolisib arm.	Drug: Palbociclib; Participants will receive oral palbociclib on Days 1-21 of each 28-day cycle.; Drug: Fulvestrant; Participants will receive intramuscular (IM) fulvestrant approximately every 4 weeks.; Drug: Placebo; Participants will receive oral placebo on Days 1-28 of each 28-day cycle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival (PFS)	PFS was defined as the time from randomization to the first occurrence of disease progression, as determined by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1 or death from any cause (whichever occurs first). Progressive disease (PD) was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum in the study, including baseline, in addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeter (mm). The appearance of one or more new lesions was also considered progression. Data for participants without the occurrence of PD or death as of the clinical cutoff date (CCOD) were censored at the time of the last tumor assessment prior to the CCOD. Median PFS was calculated using the Kaplan-Meier methodology.	Up to 3.7 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Objective Response Rate (ORR)	ORR is defined as the percentage of participants with a complete response (CR) and/or partial response (PR) on at least two consecutive occasions ≥ 4 weeks apart, as determined by the investigator according to RECIST v1.1. CR is defined as the disappearance of all target lesions or any pathological lymph nodes (whether target or non-target) having a reduction in short axis to <10 mm. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the smallest sum in the study (nadir), including baseline.	Up to approximately 6 years
Percentage of Participants With Best Overall Response Rate (BOR)	BOR is defined as the percentage of participants with a CR or PR, as determined by the investigator according to RECIST v1.1. CR is defined as the disappearance of all target lesions or any pathological lymph nodes (whether target or non-target) having a reduction in short axis to <10 mm. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the smallest sum in the study (nadir), including baseline.	Up to approximately 6 years
Duration of Response (DOR)	DOR is defined as the time from the first occurrence of a CR or PR to the first occurrence of disease progression as determined by the investigator according to RECIST v1.1, or death from any cause (whichever occurs first). CR is defined as the disappearance of all target lesions or any pathological lymph nodes (whether target or non-target) having a reduction in short axis to <10 mm. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the smallest sum in the study (nadir), including baseline. PD is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum in the study, including baseline, in addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression.	Up to approximately 6 years
Percentage of Participants With Clinical Benefit Rate (CBR)	CBR is defined as the percentage of participants with a CR, PR, and/or stable disease (SD) for at least 24 weeks, as determined by the investigator according to RECIST v1.1. CR= disappearance of all target lesions or any pathological lymph nodes (whether target or non-target) having a reduction in short axis to <10 mm. PR=at least a 30% decrease in the sum of diameters of target lesions, taking as reference the smallest sum in the study (nadir), including baseline. PD=at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum in the study (nadir), including baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression. SD=neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum in the study.	Up to approximately 6 years
Overall Survival (OS)	OS is defined as the time from randomization to death from any cause.	Up to approximately 6 years
Time to Deterioration (TTD) in Pain	TTD in pain is defined as the time from randomization to the first documentation of a ≥ 2-point increase from baseline on the "worst pain" item from the Brief Pain Inventory-Short Form (BPI-SF). BPI-SF is a self-administered questionnaire in which the participant was asked to rate severity on a 10-point scale where 0 represents 'No pain/No interference' and 10 represents 'Pain/Interference as bad as you can imagine'. A ≥2-point change is defined as clinically meaningful difference.	From randomization to first documentation of a ≥ 2-point increase (Up to approximately 6 years)
TTD in Physical Function (PF)	TTD in physical function is defined as the time from randomization to the first documentation of a ≥ 10-point decrease from baseline held for two consecutive cycles or initial decrease followed by death or treatment discontinuation within three weeks of last assessment in the European Organisation for Research and Treatment of Cancer Quality of Life-Core 30 Questionnaire (EORTC QLQ-C30) PF scale (items 1-5). A ≥10-point change is defined as a clinically meaningful difference. EORTC QLQ-C30 is a cancer-specific health-related quality-of life (QoL) questionnaire with 30 questions. For the PF scale, participant responses to 5 questions about daily activities (strenuous activities, long walks, short walks, bed/chair rest & needing help with eating, dressing, washing themselves, or using the toilet) is scored on a 4-point scale (1=Not at All to 4=Very Much). Scores are linearly transformed on a scale of 0 to 100, with a high score indicating worst functioning.	Treatment: Day 1 of Cycles 1-3, then Day 1 of every other cycle until treatment discontinuation. Post-treatment: Every 8 weeks for 2 years, then every 12 weeks thereafter, to end of study (up to 6 years) (Cycle length = 28 days)]
TTD in Role Function (RF)	TTD in Role Function is defined as the time from randomization to the first documentation of a ≥ 10-point decrease from baseline held for two consecutive cycles, or initial decrease followed by death or treatment discontinuation within three weeks of last assessment in the EORTC QLQ-C30 RF scale (items 6 and 7). A ≥10-point change is defined as clinically meaningful difference. EORTC QLQ-C30 is a cancer specific health-related QoL questionnaire. For the role functioning scale, participant responses to the 2 questions "Q6: Were you limited in doing either your work or daily activities" and "Q7: Were you limited in pursuing your hobbies or other leisure time activities" were scored on a 4-point scale (1=Not at All to 4=Very Much). The scores were linearly transformed on a scale of 0 to 100, with a low score indicating better functioning.	Treatment: Day 1 of Cycles 1-3, then Day 1 of every other cycle until treatment discontinuation. Post-treatment: Every 8 weeks for 2 years, then every 12 weeks thereafter, to end of study (up to 6 years) (Cycle length = 28 days)]
TTD in Global Health Status (GHS)	TTD in (GHS)/health-related quality of life (HRQoL) is defined as the time from randomization to the first documentation of a ≥ 10-point decrease from baseline held for two consecutive cycles, or initial decrease followed by death or treatment discontinuation within three weeks of last assessment in the EORTC QLQ-30 GHS/HRQoL scale. A ≥10-point change is defined as clinically meaningful difference. EORTC QLQ-C30 is a cancer specific health-related QoL questionnaire. Participant responses to the questions regarding Global Health Status (Q29: GHS; "How would you rate your overall health during the past week?") and Quality of Life (Q30: QoL; "How would you rate your overall quality of life during the past week?") are scored on a 7-point scale (1= Very poor to 7=Excellent). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher score indicates a better outcome.	Treatment: Day 1 of Cycles 1-3, then Day 1 of every other cycle until treatment discontinuation. Post-treatment: Every 8 weeks for 2 years, then every 12 weeks thereafter, to end of study (up to 6 years) (Cycle length = 28 days)]
Number of Participants With Adverse Events (AEs)	An AE is an untoward medical occurrence in participant administered a pharmaceutical product & regardless of causal relationship with this treatment. An AE can therefore be any unfavorable & unintended sign (including an abnormal laboratory finding), symptom/disease temporally associated with use of investigational product, whether or not considered related to investigational product.	Up to approximately 6 years
Plasma Concentration of Inavolisib		Predose on Cycle 1 Days 1, 8 and 15 and Cycle 2 Day 15; 3 hours post-dose on Cycle 1 Days 1 and 15 (Cycle length = 28 days)
Plasma Concentration of Palbociclib		Predose on Cycle 1 Days 1, 8 and 15 and Cycle 2 Day 15; 3 hours post-dose on Cycle 1 Days 1 and 15 (Cycle length = 28 days)
Plasma Concentration of Fulvestrant		Predose on Cycle 1 Days 1, 8 and 15 and Cycle 2 Day 15; 3 hours post-dose on Cycle 1 Days 1 and 15 (Cycle length = 28 days)

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche
• Investigators: Study Director: Clinical Trials, Hoffmann-La Roche

Publications and helpful links

General Publications

• Jhaveri KL, Im SA, Saura C, Loibl S, Kalinsky K, Schmid P, Loi S, Thanopoulou E, Shankar N, Jin Y, Stout TJ, Clark TD, Song C, Juric D, Turner NC. Overall Survival with Inavolisib in PIK3CA-Mutated Advanced Breast Cancer. N Engl J Med. 2025 Jul 10;393(2):151-161. doi: 10.1056/NEJMoa2501796. Epub 2025 May 31.
• Turner NC, Im SA, Saura C, Juric D, Loibl S, Kalinsky K, Schmid P, Loi S, Sunpaweravong P, Musolino A, Li H, Zhang Q, Nowecki Z, Leung R, Thanopoulou E, Shankar N, Lei G, Stout TJ, Hutchinson KE, Schutzman JL, Song C, Jhaveri KL. Inavolisib-Based Therapy in PIK3CA-Mutated Advanced Breast Cancer. N Engl J Med. 2024 Oct 31;391(17):1584-1596. doi: 10.1056/NEJMoa2404625.

Study record dates

Study Major Dates

• Study Start (Actual): January 29, 2020
• Primary Completion (Actual): September 29, 2023
• Study Completion (Estimated): November 15, 2027

Study Registration Dates

• First Submitted: December 2, 2019
• First Submitted That Met QC Criteria: December 6, 2019
• First Posted (Actual): December 9, 2019

Study Record Updates

• Last Update Posted (Actual): March 17, 2026
• Last Update Submitted That Met QC Criteria: March 13, 2026
• Last Verified: March 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; Polycyclic Compounds; Steroids; Fused-Ring Compounds; Estradiol; Estrenes; Estranes; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Fulvestrant; palbociclib; inavolisib
• Other Study ID Numbers: WO41554; 2019-002455-42 (EudraCT Number); 2023-505812-39-00 (Ctis: EU CT)

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