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

NCT04191499 | Active Not Recruiting Phase 2 Results DMC FDA Drug

• 3 other identifiers: WO415542019-002455-422023-505812-39-00
• Study Type: interventional
• Target: 325
• Locations: 28 countries
• Sites: 136

Brief Summary

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.

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (13)

• Percentage of Participants With Objective Response Rate (ORR)

  Up to approximately 6 years

• Percentage of Participants With Best Overall Response Rate (BOR)

  Up to approximately 6 years

• Duration of Response (DOR)

  Up to approximately 6 years

• Percentage of Participants With Clinical Benefit Rate (CBR)

  Up to approximately 6 years

• Overall Survival (OS)

  Up to approximately 6 years

Study Arms (2)

Inavolisib + Palbociclib + Fulvestrant

EXPERIMENTAL

Participants will receive inavolisib, palbociclib, and fulvestrant.

Drug: Inavolisib; Drug: Palbociclib; Drug: Fulvestrant

Placebo + Palbociclib + Fulvestrant

PLACEBO COMPARATOR

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: Placebo; Drug: Palbociclib; Drug: Fulvestrant

Interventions

Inavolisib DRUG

Participants will receive oral inavolisib on Days 1-28 of each 28-day cycle.

Also known as: GDC-0077

Inavolisib + Palbociclib + Fulvestrant

Placebo DRUG

Participants will receive oral placebo on Days 1-28 of each 28-day cycle.

Placebo + Palbociclib + Fulvestrant

Palbociclib DRUG

Participants will receive oral palbociclib on Days 1-21 of each 28-day cycle.

Inavolisib + Palbociclib + Fulvestrant; Placebo + Palbociclib + Fulvestrant

Fulvestrant DRUG

Participants will receive intramuscular (IM) fulvestrant approximately every 4 weeks.

Inavolisib + Palbociclib + Fulvestrant; Placebo + Palbociclib + Fulvestrant

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (136)

Beverly Hills Cancer Center

Beverly Hills, California, 90211, United States

Location

Massachusetts General Hospital.

Boston, Massachusetts, 02114, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Wake Forest University Baptist Medical Center

Winston-Salem, North Carolina, 27157, United States

Location

Sarah Cannon Research Institute / Tennessee Oncology

Chattanooga, Tennessee, 37403, United States

Location

Sarah Cannon Research Institute / Tennessee Oncology

Nashville, Tennessee, 37203, United States

Location

Texas Oncology - Central South

Austin, Texas, 78731, United States

Location

Texas Tech University Health Sciences Center

El Paso, Texas, 79905, United States

Location

Texas Oncology - Northeast Texas

Tyler, Texas, 75702, United States

Location

Northwest Medical Specialties

Tacoma, Washington, 98405, United States

Location

Centro de Investigaciones Médicas y Desarrollo LC S.R.L

Buenos Aires, Ciudad Autónoma de BuenosAires, C1113AAE, Argentina

Location

Centro Oncologico Korben

Ciudad Autonoma Buenos Aires, C1426AGE, Argentina

Location

Hosp Provincial D. Centenarios

Rosario, S2002KDS, Argentina

Location

Macquarie University Hospital

Macquarie Park, New South Wales, 2109, Australia

Location

Southern Medical Day Care Centre

Wollongong, New South Wales, 2500, Australia

Location

Mater Adult Hospital

South Brisbane, Queensland, 4101, Australia

Location

Princess Alexandra Hospital

Woolloongabba, Queensland, 4102, Australia

Location

Western Health

Fitzroy, Victoria, 3065, Australia

Location

Peninsula and South Eastern Haematology and Oncology Group

Frankston, Victoria, 3199, Australia

Location

UZ Leuven Gasthuisberg

Leuven, 3000, Belgium

Location

Santa Casa de Misericordia de Porto Alegre

Porto Alegre, Rio Grande do Sul, 90050-170, Brazil

Location

Arthur J.E. Child Comprehensive Cancer Center-Calgary

Calgary, Alberta, T2N 5G2, Canada

Location

London Regional Cancer Program, London Health Sciences Centre, Baines Centre

London, Ontario, N6A 4L6, Canada

Location

Ottawa Hospital

Ottawa, Ontario, K1H 8L6, Canada

Location

Princess Margaret Cancer Center

Toronto, Ontario, M5G 1Z5, Canada

Location

Hopital du Saint Sacrement

Québec, Quebec, G1S 4L8, Canada

Location

Beijing Cancer Hospital

Beijing, 100142, China

Location

The First Hospital of Jilin University

Changchun, 130021, China

Location

The First Affiliated Hospital, Chongqing Medical University

Chongqing, 400016, China

Location

Fujian Medical University Union Hospital

Fujian, 350001, China

Location

Sun Yet-sen University Cancer Center

Guangzhou, 510060, China

Location

Zhejiang Cancer Hospital

Hangzhou, 310022, China

Location

Harbin Medical University Cancer Hospital

Harbin, 150081, China

Location

Fudan University Shanghai Cancer Center

Shanghai, 201315, China

Location

Hebei Medical University Fourth Hospital

Shijiazhuang, 050035, China

Location

Tianjin Cancer Hospital

Tianjin, 300060, China

Location

Hubei Cancer Hospital

Wuhan, 430079, China

Location

First Affiliated Hospital of Medical College of Xi'an Jiaotong University

Xi'an, 710061, China

Location

Henan Cancer Hospital

Zhengzhou, 450008, China

Location

Vejle Sygehus

Vejle, 7100, Denmark

Location

Centre Jean Perrin Centre Regional de Lutte Contre Le Cancer D auvergne

Clermont-Ferrand, 63003, France

Location

Centre Georges Francois Leclerc

Dijon, 21079, France

Location

Centre Oscar Lambret

Lille, 59020, France

Location

Hopital Prive Jean Mermoz

Lyon, 69373, France

Location

Institut régional du Cancer Montpellier

Montpellier, 34298, France

Location

Institut Universitaire du Cancer de Toulouse-Oncopole

Toulouse, 31059, France

Location

Israel-Georgian Medical Research Clinic Healthycore

Tbilisi, 0112, Georgia

Location

Tbilisi Oncology Dispensary

Tbilisi, 0159, Georgia

Location

Ambulantes Tumorzentrum Spandau

Berlin, 13581, Germany

Location

Klinikum Essen-Mitte Ev. Huyssens-Stiftung / Knappschafts GmbH

Essen, 45136, Germany

Location

Nationales Centrum für Tumorerkrankungen (NCT)

Heidelberg, 69120, Germany

Location

Universitätsklinikum Mannheim

Mannheim, 68167, Germany

Location

Klinikum Mutterhaus der Borromaeerinnen gGmbH

Trier, 54290, Germany

Location

Universitätsfrauenklinik Ulm

Ulm, 89075, Germany

Location

Anticancer Hospital Ag. Savas

Athens, 115 22, Greece

Location

Univ General Hosp Heraklion

Heraklion, 711 10, Greece

Location

Euromedical General Clinic of Thessaloniki

Thessaloniki, 546 45, Greece

Location

European Interbalkan Medical Center

Thessaloniki, 570 01, Greece

Location

Queen Mary Hospital

Hong Kong, Hong Kong

Location

Orszagos Onkologiai Intezet

Budapest, 1122, Hungary

Location

Uzsoki Utcai Korhaz

Budapest, 1145, Hungary

Location

Jasz-Nagykun-Szolnok Megyei Hetenyi Geza Korhaz-Rendelointezet

Szolnok, 5004, Hungary

Location

A.O. Universitaria Di Parma

Parma, Emilia-Romagna, 43100, Italy

Location

Az. Osp. Spedali Civili

Brescia, Lombardy, 25123, Italy

Location

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, Lombardy, 20133, Italy

Location

Ospedale Santa Maria Annunziata

Bagno a Ripoli, Tuscany, 50012, Italy

Location

IOV - Istituto Oncologico Veneto - IRCCS

Padua, Veneto, 35128, Italy

Location

National Cancer Institute IKN

Putrajaya, Federal Territory of Putrajaya, 62250, Malaysia

Location

Hospital Sultan Ismail

Johor Bahru, Johor, 81100, Malaysia

Location

Sarawak General Hospital

Sarawak, Sarawak, 93586, Malaysia

Location

Palmerston North Hospital

Palmerston North, 4442, New Zealand

Location

Narodowy Instytut Onkologii Odzia? w Gliwicach

Gliwice, 44-102, Poland

Location

Przychodnia Lekarska KOMED, Roman Karaszewski

Konin, 625000, Poland

Location

Narodowy Inst.Onkologii im.Sklodowskiej-Curie Panstw.Inst.Bad

Warsaw, 02-781, Poland

Location

Centro Clinico Champalimaud

Lisbon, 1400-038, Portugal

Location

IPO do Porto

Porto, 4200-072, Portugal

Location

Moscow Clinical Scientific Center

Moscow, Moscow Oblast, 111123, Russia

Location

Blokhin Cancer Research Center

Moscow, Moscow Oblast, 115552, Russia

Location

MEDSI Clinical Hospital on Pyatnitsky Highway

Moscow, Moscow Oblast, 143422, Russia

Location

LLC Medscan

Moskva, Moscow Oblast, 119421, Russia

Location

Clinical Hospital Lapino (LLC Haven)

Yudino, Moscow Oblast, 143081, Russia

Location

Medical Clinic "AB Medical group"

Saint Petersburg, Sankt-Peterburg, 197082, Russia

Location

Volgograd Regional Clinical Oncology Dispensary

Volgograd, 400138, Russia

Location

Regional Clinical Oncology Hospital

Yaroslavl, 150040, Russia

Location

National University Hospital

Singapore, 119228, Singapore

Location

National Cancer Centre

Singapore, 168583, Singapore

Location

Pusan National University Hospital

Busan, 49241, South Korea

Location

Kyungpook National University Medical Center

Daegu, 41404, South Korea

Location

National Cancer Center

Gyeonggi-do, 10408, South Korea

Location

Seoul National University Bundang Hospital

Gyeonggi-do, 13620, South Korea

Location

Korea University Anam Hospital

Seoul, 02841, South Korea

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Severance Hospital, Yonsei University Health System

Seoul, 03722, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Gangnam Severance Hospital

Seoul, 06273, South Korea

Location

Ewha Womans University Mokdong Hospital

Seoul, 07985, South Korea

Location

Samsung Medical Center

Seoul, 6351, South Korea

Location

Hospital Universitari Germans Trias i Pujol

Badalona, Barcelona, 08916, Spain

Location

Clinica Universitaria de Navarra

Pamplona, Navarre, 31008, Spain

Location

Hospital Universitario de Canarias

San Cristóbal de La Laguna, Tenerife, 38320, Spain

Location

Hospital del Mar

Barcelona, 08003, Spain

Location

Vall d?Hebron Institute of Oncology (VHIO), Barcelona

Barcelona, 08035, Spain

Location

Insituto Catalán de Oncologia (ICO)

Barcelona, 08907, Spain

Location

Complejo Hospitalario de Jaen-Hospital Universitario Medico Quirurgico

Jaén, 23007, Spain

Location

Hospital General Universitario Gregorio Marañon

Madrid, 28007, Spain

Location

Clinica Universidad de Navarra-Madrid

Madrid, 28027, Spain

Location

Hospital Clinico San Carlos

Madrid, 28040, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Universitario Puerta de Hierro

Madrid, 28222, Spain

Location

Hospital Universitario Virgen Macarena

Seville, 41009, Spain

Location

Instituto Valenciano Oncologia

Valencia, 46009, Spain

Location

Hospital Clinico Universitario de Valencia

Valencia, 46010, Spain

Location

Kaohsiung Medical Uni Chung-Ho Hospital

Kaohsiung City, 807, Taiwan

Location

Veterans General Hospital

Taipei, 00112, Taiwan

Location

National Taiwan Uni Hospital

Taipei, 100, Taiwan

Location

Koo Foundation Sun Yat-Sen Cancer Center

Taipei, 112, Taiwan

Location

Tri-Service General Hospital, Division of General Surgery

Taipei, 114, Taiwan

Location

Ramathibodi Hospital

Bangkok, 10400, Thailand

Location

Maharaj Nakorn Chiang Mai Hospital

Chiang Mai, 50200, Thailand

Location

Chulabhorn Hospital

Lak Si, 10210, Thailand

Location

Songklanagarind Hospital

Songkhla, 90110, Thailand

Location

Adana Baskent University Hospital

Adana, 01120, Turkey (Türkiye)

Location

Gulhane Training and Research Hospital

Ankara, 06010, Turkey (Türkiye)

Location

Ege University Medical Faculty

Bornova, ?zm?r, 35100, Turkey (Türkiye)

Location

Istanbul University Cerrahpasa Faculty of Medicine

Istanbul, 34098, Turkey (Türkiye)

Location

Prof. Dr. Cemil Tascioglu City Hospital

Istanbul, 34384, Turkey (Türkiye)

Location

SI Institute of general&urgent surgery n/a Zaytseva V.T NAMSU

Kharkiv, Kharkiv Governorate, 61018, Ukraine

Location

Municipal Institution SubCarpathian Clinical Oncological Centre

Ivano-Frankivsk, KIEV Governorate, 76018, Ukraine

Location

Uzhhorod Central City Clinical Hospital

Uzhhorod, KIEV Governorate, 88000, Ukraine

Location

City Clinical Hospital #4

Dnipropetrovsk, 49102, Ukraine

Location

ME Kryviy Rih Oncology Dispensary of Dnipropetrovs?k Regional Council

Kryvyi Rih, 50048, Ukraine

Location

Kyiv City Clinical Oncological Center

Kyiv, 03115, Ukraine

Location

Royal Marsden Hospital - Fulham

London, SW3 6JJ, United Kingdom

Location

Mount Vernon Hospital

Northwood, HA6 2RN, United Kingdom

Location

Churchill Hospital

Oxford, OX3 7LJ, United Kingdom

Location

Derriford Hospital

Plymouth, PL6 8DH, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 40454641 DERIVED

• 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.

  PMID: 39476340 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

inavolisib; palbociclib; Fulvestrant

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800 821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 2, 2019
• First Posted: December 9, 2019
• Study Start: January 29, 2020
• Primary Completion: September 29, 2023
• Study Completion (Estimated): November 15, 2027
• Last Updated: March 17, 2026
• Results First Posted: October 9, 2024

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

PT (2); GB (4); PL (3); GE (2); SG (2); GR (4); ES (15); HU (3); BR (1); DE (6); HK (1); CN (13); CA (5); BE (1); FR (6); NZ (1); RU (8); TH (4); DK (1); AR (3); AU (6); TW (5); TU (5); UA (6); MY (3); US (10); IT (5); KR (11)