A Study of Ipatasertib in Combination With Atezolizumab and Paclitaxel as a Treatment for Participants With Locally Advanced or Metastatic Triple-Negative Breast Cancer

A Phase III, Double-blind, Placebo-controlled, Randomized Study of Ipatasertib in Combination With Atezolizumab and Paclitaxel as a Treatment for Patients With Locally Advanced Unresectable or Metastatic Triple-Negative Breast Cancer

This study evaluated the efficacy and safety of ipatasertib in combination with atezolizumab and paclitaxel in locally advanced or metastatic Triple-Negative Breast Cancer (TNBC) previously untreated in this setting.

Study Overview

• Status: Completed
• Conditions: Triple-Negative Breast Cancer
• Intervention / Treatment: Drug: Atezolizumab; Drug: Ipatasertib; Drug: Paclitaxel; Drug: Placebo for Atezolizumab; Drug: Placebo for Ipatasertib

Detailed Description

This study will evaluate the efficacy, safety and pharmacokinetics of ipatasertib in combination with atezolizumab and paclitaxel in locally advanced unresectable or metastatic triple-negative breast cancer (TNBC) previously untreated in this setting. Participants with Programmed Death-Ligand 1 (PD-L1) non-positive and PD-L1 positive tumors will be independently enrolled in Cohorts 1 and 2, respectively. The combination of ipatasertib, atezolizumab and paclitaxel will be evaluated in Cohorts 1 and 2 and the combination of ipatasertib and paclitaxel will be evaluated in Cohort 1.

• Study Type: Interventional
• Enrollment (Actual): 242
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1125ABD
    • Fundación CENIT para la Investigación en Neurociencias
  • Buenos Aires, Argentina, C1417DTB
    • Inst. Angel Roffo; Haematology
  • Ciudad Autonoma Bs As, Argentina, C1280AEB
    • Hospital Britanico
  • Cordoba, Argentina, X5800AEU
    • Instituto Medico Rio Cuarto
  • La Rioja, Argentina, F5300COE
    • Centro Oncologico Riojano Integral (Cori)
  • Mendoza, Argentina, M5500AYB
    • Fundacion Scherbovsky
• Australia
  • New South Wales
    • Macquarie Park, New South Wales, Australia, 2109
      • Macquarie University Hospital
    • Port Macquarie, New South Wales, Australia, 2444
      • Mid North Coast Cancer Institute
    • St Leonards, New South Wales, Australia, 2065
      • Royal North Shore Hospital; Department of Medical Oncology
    • Waratah, New South Wales, Australia, 2298
      • Calvary Mater Newcastle; Medical Oncology
  • Queensland
    • Woolloongabba, Queensland, Australia, 4102
      • Princess Alexandra Hospital
  • South Australia
    • Kurralta Park, South Australia, Australia, 5037
      • Adelaide Cancer Centre
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Monash Health Monash Medical Centre
    • Melbourne, Victoria, Australia, 3000
      • Peter MacCallum Cancer Centre; Medical Oncology
    • St Albans, Victoria, Australia
      • Sunshine Hospital; Oncology Research
  • Western Australia
    • Subiaco, Western Australia, Australia, 6008
      • St John of God Hospital; Bendat Cancer Centre
• Austria
  • Innsbruck, Austria, 6020
    • Tiroler Landeskrankenanstalten Ges.M.B.H.; Abt. Für Gynäkologie
  • Linz, Austria, 4010
    • Ordensklinikum Linz Barmherzige Schwestern; Interne 1 - Hämato-Onkologie
  • Salzburg, Austria, 5020
    • Uniklinikum Salzburg, LKH; Univ.Klinik f. Innere Medizin III der PMU
  • Wien, Austria, 1090
    • Medizinische Universität Wien; Univ.Klinik für Innere Medizin I
• Belgium
  • Gent, Belgium, 9000
    • AZ Maria Middelares
  • Hasselt, Belgium, 3500
    • Jessa Zkh (Campus Virga Jesse)
• Brazil
  • BA
    • Salvador, BA, Brazil, 41253-190
      • Hospital Sao Rafael - HSR
  • RS
    • Porto Alegre, RS, Brazil, 90035-903
      • Hospital das Clinicas - UFRGS
  • SP
    • Sao Paulo, SP, Brazil, 01317-001
      • Clinica de Pesquisa e Centro de Estudos em Oncologia Ginecologica e Mamaria Ltda
    • Sao Paulo, SP, Brazil, 04014-002
      • Núcleo de Pesquisa São Camilo; ONCOLOGIA CLINICA / QUIMIOTERAPIA
• Bulgaria
  • Sofia, Bulgaria, 1330
    • MHAT Nadezhda
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Cross Cancer Institute ; Dept of Medical Oncology
  • British Columbia
    • Surrey, British Columbia, Canada, V3V 1Z2
      • Fraser Valley Centre British Columbia Cancer Agency
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3E 0V9
      • Cancer Care Manitoba
  • Ontario
    • Barrie, Ontario, Canada, L4M 6M2
      • Royal Victoria Hospital
    • Ottawa, Ontario, Canada, K2H 6C2
      • The Ottawa Hospital Cancer Centre
  • Quebec
    • Montreal, Quebec, Canada, H4A 3J1
      • McGill University; Glen Site; Oncology
    • Montréal, Quebec, Canada, H3T 1E2
      • Jewish General Hospital; Research Unit
    • Quebec City, Quebec, Canada, G1S 4L8
      • Hopital du Saint Sacrement
• Colombia
  • Bogota, Colombia, 11001
    • Clínica del Country
  • Pereira, Colombia, 600004
    • Oncólogos de Occidente
• Costa Rica
  • San José, Costa Rica, 10103
    • Clinica CIMCA
• Czechia
  • Brno, Czechia, 656 53
    • Masaryk?v onkologický ústav; Klinika komplexní onkologické pé?e
  • Olomouc, Czechia, 779 00
    • Fakultni nemocnice Olomouc; Onkologicka klinika
• Denmark
  • Herlev, Denmark, 2730
    • Herlev Hospital; Afdeling for Kræftbehandling
  • Odense C, Denmark, 5000
    • Odense Universitetshospital, Onkologisk Afdeling R
• Finland
  • Helsinki, Finland, 00180
    • Docrates Cance Center
  • Kuopio, Finland, 70210
    • KYS Sadesairaala; Syopatautien poliklinikka
  • Vaasa, Finland, 65130
    • VAASAN KESKUSSAIRAALA; Onkologian poliklinikka
• France
  • Rennes, France, 35042
    • Centre Eugene Marquis; Service d'oncologie
• Greece
  • Kifisia, Greece, 145 64
    • Agioi Anargyroi Cancer Hospital; 2Nd Oncology Dept.
  • Thessaloniki, Greece, 546 45
    • Euromedical General Clinic of Thessaloniki; Oncology Department
• Hong Kong
  • Hong Kong, Hong Kong
    • Queen Mary Hospital; Dept of Medicine
  • Hong Kong, Hong Kong
    • Tuen Mun Hospital; Clinical Onc
  • Shatin, Hong Kong
    • Prince of Wales Hospital; Department of Clinical Onocology
• India
  • Maharashtra
    • Pune, Maharashtra, India, 411028
      • Sahyadri Super Specialty Hospital Hadapsar
• Israel
  • Jerusalem, Israel, 9103102
    • Shaare Zedek Medical Center
• Italy
  • Campania
    • Napoli, Campania, Italy, 80131
      • Istituto Nazionale per lo Studio e la Cura dei Tumori Fondazione G. Pascale
  • Emilia-Romagna
    • Meldola, Emilia-Romagna, Italy, 47014
      • IRST Istituto Scientifico Romagnolo Per Lo Studio E Cura Dei Tumori, Sede Meldola; Oncologia Medica
  • Friuli-Venezia Giulia
    • Udine, Friuli-Venezia Giulia, Italy, 33100
      • ASU FC S. M. DELLA MISERICORDIA; Oncologia
  • Lombardia
    • Brescia, Lombardia, Italy, 25123
      • ASST DEGLI SPEDALI CIVILI DI BRESCIA; Oncologia Medica
    • Lecco, Lombardia, Italy, 23900
      • ASST DI LECCO; Oncologia Medica
    • Rozzano (MI), Lombardia, Italy, 20089
      • IRCCS Istituto Clinico Humanitas; Oncologia
  • Toscana
    • Livorno, Toscana, Italy, 57100
      • Ospedale Civile; Unita Operativa Di Oncologia Medica
  • Veneto
    • Padova, Veneto, Italy, 35128
      • IOV - Istituto Oncologico Veneto - IRCCS; Oncologia Medica II
• Japan
  • Aichi, Japan, 464-8681
    • Aichi Cancer Center Hospital
  • Fukushima, Japan, 960-1295
    • Fukushima Medical University Hospital
  • Gunma, Japan, 373-8550
    • Gunma Prefectural Cancer Center
  • Hiroshima, Japan, 734-8551
    • Hiroshima University Hospital
  • Kanagawa, Japan, 241-8515
    • Kanagawa Cancer Center
  • Kumamoto, Japan, 862-8655
    • Kumamoto Shinto General Hospital
  • Okayama, Japan, 700-8558
    • Okayama University Hospital
  • Osaka, Japan, 541-8567
    • Osaka International Cancer Institute
• Korea, Republic of
  • Daegu, Korea, Republic of, 41404
    • Kyungpook National University Medical Center
  • Goyang-si, Korea, Republic of, 10408
    • National Cancer Center
  • Seoul, Korea, Republic of, 03722
    • Severance Hospital, Yonsei University Health System
  • Seoul, Korea, Republic of, 05505
    • Asan Medical Center
  • Seoul, Korea, Republic of, 06351
    • Samsung Medical Center
  • Seoul, Korea, Republic of, 06591
    • Seoul St Mary's Hospital
• Mexico
  • BAJA California SUR
    • La Paz, BAJA California SUR, Mexico, 23040
      • Investigacion Oncofarmaceutica
  • Mexico CITY (federal District)
    • Cdmx, Mexico CITY (federal District), Mexico, 03100
      • Health Pharma Professional Research
  • Nuevo LEON
    • Monterrey, Nuevo LEON, Mexico, 64570
      • Christus Muguerza Clinica Vidriera
• New Zealand
  • Auckland, New Zealand, 1023
    • Auckland City Hospital, Cancer and Blood Research
  • Tauranga, New Zealand, 3112
    • Tauranga Hospital, Clinical Trials Unit; BOP Clinical School
  • Wellington, New Zealand, 6021
    • Wellington Regional Hospital; Clinical Trials Unit
• Peru
  • Arequipa, Peru, 04001
    • Centro Medico Monte Carmelo
  • Arequipa, Peru, 04002
    • Instituto Regional de Enfermedades Neoplasicas
  • Lima, Peru, Lima 34
    • Instituto Nacional de Enfermedades Neoplasicas
  • Lima, Peru, 07016
    • Unidad de Investigación Oncologica; Hospital Nacional Daniel Alcides Carrion
  • Lima, Peru, 15088
    • Clínica San Gabriel; Unidad de Investigación Oncológica de la Clínica San Gabriel
  • Lima, Peru, 1
    • Hospital Arzobispo Loayza
  • Lima, Peru, 41
    • Oncosalud Sac; Oncología
  • San Isidro, Peru, Lima 27
    • Clinica Ricardo Palma
• Poland
  • ?ód?, Poland, 93-338
    • Instyt. Centrum Zdrowia Matki Polki; Klinika Chirurgii Onk. Chorób Piersi z Podod. Onko Klinicznej
  • Gliwice, Poland, 44-101
    • Narodowy Inst.Onkol.im.Sklodowskiej-Curie Panstw.Inst.Bad Gliwice; Centr.Diagn.i Lecz.Chor.Piersi
  • Kraków, Poland, 30-688
    • Szpital Uniwersytecki w Krakowie, Oddzia? Kliniczny Kliniki Onkologii
  • Poznan, Poland, 61-866
    • Wielkopolskie Centrum Onkologii
  • Warszawa, Poland, 02-781
    • Narodowy Instytut Onkologii im. M.Sklodowskiej-Curie; Klinika Nowotworow Piersi i Chirurgii Rekonstr
• Portugal
  • Lisboa, Portugal, 1500-650
    • Hospital da Luz; Departamento de Oncologia Medica
  • Lisboa, Portugal, 1649-035
    • Hospital de Santa Maria; Servico de Oncologia Medica
  • Loures, Portugal, 2674-514
    • Hospital Beatriz Angelo; Departamento de Oncologia
  • Porto, Portugal, 4200-072
    • IPO do Porto; Servico de Oncologia Medica
  • Porto, Portugal, 4099-001
    • Centro Hospitalar do Porto ? Hospital de Santo António; Oncologia
• Romania
  • Craiova, Romania, 200347
    • Oncology Center Sf. Nectarie
• Russian Federation
  • Novosibirsk, Russian Federation, 630005
    • Limited Liability Company "RC Medical"
  • Arhangelsk
    • Arkhangelsk, Arhangelsk, Russian Federation, 163045
      • Arkhangelsk Regional Clinical Oncology Dispensary
  • Moskovskaja Oblast
    • Moscow, Moskovskaja Oblast, Russian Federation, 121467
      • University ?linic of headaches
    • Moscow, Moskovskaja Oblast, Russian Federation, 125284
      • P.A. Gertsen Cancer Research Inst. ; Chemotherapy Dept
    • Moskva, Moskovskaja Oblast, Russian Federation, 111123
      • SBIH "Moscow Clinical Scientific and Practical Center named after A.S. Loginov of DHM"
    • Moskva, Moskovskaja Oblast, Russian Federation, 115478
      • Fed State Budgetary Inst "N.N. Blokhin Med Center of Oncology" MHRF
    • Moskva, Moskovskaja Oblast, Russian Federation, 125367
      • FSAI Treatment and rehabilitation Centre Ministry of Health; Clinical research and chemotherapy.
  • Sankt Petersburg
    • Saint-Petersburg, Sankt Petersburg, Russian Federation, 197758
      • S-Pb clinical scientific practical center of specialized kinds of medical care (oncological)
  • Tatarstan
    • Kazan, Tatarstan, Russian Federation, 420029
      • Clinical Oncology Dispensary of Ministry of Health of Tatarstan
• Singapore
  • Singapore, Singapore, 168583
    • National Cancer Centre; Medical Oncology
• South Africa
  • Bloemfontein, South Africa, 9301
    • National Hospital; Oncotherapy Dept
  • George, South Africa, 6529
    • Cancercare
  • Johannesberg, South Africa, 2013
    • Wits Clinical Research
  • Port Elizabeth, South Africa, 6045
    • Cancercare
  • Pretoria, South Africa, 0001
    • Wilgers Oncology Centre
• Spain
  • Barcelona, Spain, 08036
    • Hospital Clínic i Provincial; Servicio de Hematología y Oncología
  • Madrid, Spain, 28034
    • Hospital Ramon y Cajal; Servicio de Oncologia
  • Madrid, Spain, 28040
    • Hospital Universitario Clínico San Carlos; Servicio de Oncologia
  • Madrid, Spain, 28007
    • Hospital General Universitario Gregorio Marañon; Servicio de Oncologia
  • Madrid, Spain, 28050
    • Centro Integral Oncologico Clara Campal; Servicio de Oncología
  • Malaga, Spain, 29010
    • Hospital Clinico Universitario Virgen de la Victoria; Servicio de Oncologia
  • Valencia, Spain, 46010
    • Hospital Clínico Universitario de Valencia; Servicio de Oncología
  • Barcelona
    • Sant Andreu de La Barca, Barcelona, Spain, 08740
      • Hospital Univ Vall d'Hebron; Servicio de Oncologia
  • Castellon
    • Castellon de La Plana, Castellon, Spain, 12002
      • Hospital Provincial de Castellon; Servicio de Oncologia
  • LA Coruña
    • A Coruña, LA Coruña, Spain, 15006
      • Complejo Hospitalario Universitario A Coruña (CHUAC); Servicio de Oncologia
  • Madrid
    • Majadahonda, Madrid, Spain, 28222
      • Hospital Universitario Puerta de Hierro; Servicio de Oncologia
• Switzerland
  • Basel, Switzerland, 4031
    • Universitätsspital Basel
  • Zürich, Switzerland, 8091
    • Universitätsspital Zürich Gynäkologische Klinik; Klinik für Gynäkologie
• Taiwan
  • Taichung, Taiwan, 404
    • China Medical University Hospital; Surgery
  • Taipei, Taiwan, 00112
    • VETERANS GENERAL HOSPITAL; Department of General Surgery
  • Taipei, Taiwan, 100
    • National Taiwan Uni Hospital; General Surgery
  • Taoyuan City, Taiwan, 333
    • Chang Gung Memorial Hosipital at Linkou
• Thailand
  • Bangkok, Thailand, 10330
    • Chulalongkorn Hospital; Medical Oncology
  • Bangkok, Thailand, 10700
    • Faculty of Med. Siriraj Hosp.; Med.-Div. of Med. Oncology
  • Bangkok, Thailand, 10400
    • Rajavithi Hospital; Division of Medical Oncology
  • Chiang Mai, Thailand, 50200
    • Maharaj Nakorn Chiang Mai Hospital; Department of Surgery/Head Neck and Breast Unit; Clinical Trial
  • Khonkaen, Thailand, 40000
    • Khonkaen Hospital
  • Songkhla, Thailand, 90110
    • Songklanagarind Hospital; Department of Oncology
• Turkey
  • Ankara, Turkey, 06520
    • Memorial Ankara Hastanesi
  • Istanbul, Turkey, 34214
    • Medipol University Medical Faculty; Oncology Department
  • Sihhiye/Ankara, Turkey, 06230
    • Hacettepe Uni Medical Faculty Hospital; Oncology Dept
• Ukraine
  • Chernigiv, Ukraine, 14029
    • Regional Oncology Center; Department of Mammology
  • Dnipropetrovsk, Ukraine, 49102
    • Chemotherapy SI Dnipropetrovsk MA of MOHU
  • Kryvyi Rih, Ukraine, 50048
    • ME Kryviy Rih Oncology Dispensary of Dnipropetrovs?k Regional Council; Chemotherapy Department
  • Kyiv, Ukraine, 04107
    • MI Kyiv Regional Council Kyiv Regional Oncological Dispensary; Department of Mammology
  • Odesa, Ukraine, 65025
    • Municipal Institution Odesa Regional Clinical Hospital
  • Sumy, Ukraine, 40005
    • RCI Sumy Regional Clinical Oncological Dispensary
  • Kharkiv Governorate
    • Kharkiv, Kharkiv Governorate, Ukraine, 61018
      • SI Institute of general&urgent surgery n/a Zaytseva V.T NAMSU; Purulent Surgery department
• United Kingdom
  • Glasgow, United Kingdom, G12 0YN
    • BEATSON WEST OF SCOTLAND CANCER CENTRE; Clinical Research Unit ? Level 1
  • London, United Kingdom, SW3 6JJ
    • The Royal Marsden Hospital, Fulham
  • Nottingham, United Kingdom, NG7 2UH
    • Nottingham University Hospitals NHS Trust
• United States
  • Alabama
    • Mobile, Alabama, United States, 36688
      • USA Mitchell Cancer Institute
  • Arkansas
    • Springdale, Arkansas, United States, 72762
      • Highlands Oncology Group
  • California
    • Los Angeles, California, United States, 90095
      • UCLA
    • San Diego, California, United States, 92108
      • Kaiser Permanente-SCPMG; Oncology Research
    • Stanford, California, United States, 94305-5820
      • Stanford Cancer Center
  • Colorado
    • Denver, Colorado, United States, 80205
      • Kaiser Permanente - Franklin
  • Connecticut
    • Stamford, Connecticut, United States, 06904
      • Stamford Hospital; BCC, MOHR
  • Florida
    • Fort Lauderdale, Florida, United States, 33308
      • Holy Cross Hospital
    • Hollywood, Florida, United States, 33021
      • Memorial Healthcare System - Memorial Regional Hospital
    • Pembroke Pines, Florida, United States, 33028
      • Memorial Cancer Institute at Memorial West
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Winship Cancer Institute
    • Savannah, Georgia, United States, 31405
      • Nancy N. and J.C. Lewis Cancer & Research Pavillion -St. Josephs / Candler Health System-CCD PRIME
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70809
      • Ochsner Clinic Foundation
    • New Orleans, Louisiana, United States, 70121
      • Ochsner Health System
  • Maryland
    • Baltimore, Maryland, United States, 21202
      • Mercy Medical Center
    • Baltimore, Maryland, United States, 21201
      • University of Maryland Medical Center
    • Baltimore, Maryland, United States, 21237
      • MedStar Franklin Square Medical Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48106
      • St. Joseph Mercy Hospital; Cancer Care Center.
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System
  • Mississippi
    • Jackson, Mississippi, United States, 39202
      • Jackson Oncology Associates, PLLC
  • Nebraska
    • Grand Island, Nebraska, United States, 68803
      • CHI Health Saint Francis; Oncology
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth Hitchcock Medical Center
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Hackensack Univ Med Ctr
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University Baptist Medical Center
  • Oregon
    • Portland, Oregon, United States, 97227
      • Kaiser Permanente - Portland
    • Portland, Oregon, United States, 97229
      • Oregon Health and Science University
  • South Carolina
    • Charleston, South Carolina, United States, 29414
      • Charleston Oncology, P .A
    • Greenville, South Carolina, United States, 29605-4292
      • Greenville Health System; Cancer Center
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • The West Clinic; West Cancer Center
    • Nashville, Tennessee, United States, 37203
      • Vanderbilt Univ Medical Ctr

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Willingness and ability to complete all study-related assessments, including Participant-Reported Outcome (PRO) assessments, in the investigator's judgement.
2. Adequate hematologic and organ function within 14 days before the first study treatment on Day 1 of Cycle 1.
3. Life expectancy of at least 6 months.
4. Measurable disease according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v 1.1).
5. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
6. For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception, and agreement to refrain from donating eggs.
7. For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods, and agreement to refrain from donating sperm.
8. Appropriate candidate for paclitaxel monotherapy if tumor programmed death-ligand 1 (PD-L1) status is unknown or non-positive; appropriate candidate for paclitaxel and atezolizumab if tumor PD-L1 status is positive.
9. Histologically documented triple-negative adenocarcinoma of the breast that is locally advanced or metastatic and is not amenable to resection with curative intent.

Exclusion Criteria:

1. Inability to comply with study and follow-up procedures.
2. History of malabsorption syndrome or other condition that would interfere with enteral absorption or results in the inability or unwillingness to swallow pills.
3. Severe infection within 4 weeks prior to initiation of study treatment (including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia) as well as those who have received treatment with therapeutic oral or intravenous (IV) antibiotics within 2 weeks prior to initiation of study treatment.
4. Known human immunodeficiency virus (HIV) infection (there must be a negative HIV test at screening).
5. Known clinically significant history of liver disease consistent with Child-Pugh Class B or C.
6. Current treatment with anti-viral therapy for hepatitis B virus (HBV).
7. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 1 of Cycle 1 or anticipation of need for a major surgical procedure during the study.
8. Pregnancy or breastfeeding, or intention to become pregnant during the study or within 28 days after the final dose of ipatasertib or (/) placebo, 5 months after the final dose of atezolizumab/placebo, and 6 months after the final dose of paclitaxel whichever occurs later.
9. New York Heart Association Class II, III, or IV heart failure, left ventricular ejection fraction less than (<) 50 percent (%), or active ventricular arrhythmia requiring medication.
10. Current unstable angina or history of myocardial infarction within 6 months prior to Day 1 of Cycle 1.
11. Congenital long QT syndrome or screening QT interval corrected through use Fridericia's formula (QTcF) greater than (>) 480 milliseconds (ms).
12. Current treatment with medications used at doses known to cause clinically relevant prolongation of QT/QTc interval.
13. History or presence of an abnormal ECG that is clinically significant in the investigator's opinion (including complete left bundle branch block, second- or third-degree heart block, or evidence of prior myocardial infarction).
14. Requirement for chronic corticosteroid therapy of > 10 mg of prednisone per day or an equivalent dose of other anti-inflammatory corticosteroids or immunosuppressant agents for a chronic disease.
15. Treatment with approved or investigational cancer therapy within 14 days prior to Day 1 of Cycle 1.
16. Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that, in the investigator's opinion, gives reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or renders the participant at high risk from treatment complications.
17. History of or known presence of spinal cord metastases, as determined by computed tomography (CT) or magnetic resonance imaging (MRI) evaluation during screening or prior radiographic assessments.
18. Known central nervous system (CNS) disease, except for treated asymptomatic CNS metastases.
19. Known germline breast cancer gene (BRCA)1/2 deleterious mutation, unless the participant is not an appropriate candidate for a poly adenosine diphosphate ribose polymerase (PARP)-inhibitor.
20. Any previous systemic therapy for inoperable locally advanced or metastatic triple-negative adenocarcinoma of the breast.
21. Unresolved, clinically significant toxicity from prior therapy, except for alopecia and Grade 1 peripheral neuropathy.
22. Participants who have received palliative radiotherapy to peripheral sites (e.g., bone metastases) for pain control and whose last treatment was completed 14 days prior to Day 1 of Cycle 1 may be enrolled in the study if they have recovered from all acute, reversible effects (e.g., to Grade 1 or resolved by enrolment).
23. Uncontrolled pleural effusion, pericardial effusion or ascites.
24. Uncontrolled tumor-related pain.
25. Malignancies other than breast cancer within 5 years prior to Day 1 of Cycle 1, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or Stage I uterine cancer.
26. Known hypersensitivity or contraindication to any component of the study treatments, including the paclitaxel excipient, macrogolglycerol ricinoleate.
27. Grade greater than or equal to (≥) 2 peripheral neuropathy.
28. History of Type I or Type II diabetes mellitus requiring insulin.
29. Grade ≥ 2 uncontrolled or untreated hypercholesterolemia or hypertriglyceridemia.
30. History of or active inflammatory bowel disease (e.g., Crohn disease and ulcerative colitis) or active bowel inflammation (e.g., diverticulitis).
31. Lung disease: pneumonitis, interstitial lung disease, idiopathic pulmonary fibrosis, cystic fibrosis, Aspergillosis, active tuberculosis, or history of opportunistic infections (pneumocystis pneumonia or cytomegalovirus pneumonia).
32. Treatment with strong Cytochrome P450 (CYP)3A inhibitors or strong CYP3A inducers within 2 weeks or 5 drug-elimination half-lives, whichever is longer, prior to initiation of study drug.
33. Prior treatment with an Protein kinase B (Akt) inhibitor.
34. Active or history of autoimmune disease or immune deficiency.
35. History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan.
36. Prior allogeneic stem cell or solid organ transplantation.
37. Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, or anticipation of need for such a vaccine during treatment with atezolizumab or within 5 months after the final dose of atezolizumab.
38. History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins.
39. Known hypersensitivity to Chinese hamster ovary cell products or recombinant human antibodies.
40. Treatment with systemic immunostimulatory agents (including, but not limited to, interferon and interleukin-2) within 4 weeks or 5 half-lives of the drug (whichever is longer) prior to initiation of study treatment.
41. Treatment with systemic immunosuppressive medication (including, but not limited to corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor-alpha agents) within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressive medication during the study.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1 Arm A: Ipatasertib + Atezolizumab + Paclitaxel; TNBC participants with programmed death-ligand 1 (PD-L1) non-positive received a combination of paclitaxel, 80 milligrams per meter square (mg/m^2), intravenous (IV) infusion on Days 1, 8, and 15 of each 28-day cycle and ipatasertib, 400 mg, orally (PO), once daily (QD), from Day 1 to Day 21 of each 28-day cycle and atezolizumab, 840 mg, IV infusion on Day 1 and 15 of each 28-day cycle until loss of clinical benefit, unacceptable toxicity, or withdrawal of consent, whichever occurred first.	Drug: Atezolizumab; Atezolizumab was administered as per the dosage regimen mentioned in arm descriptions.; Drug: Ipatasertib; Ipatasertib was administered as per the dosage regimen mentioned in arm descriptions.; Drug: Paclitaxel; Paclitaxel was administered as per the dosage regimen mentioned in arm descriptions.
Experimental: Cohort 1 Arm B: Ipatasertib + Placebo + Paclitaxel; TNBC participants with PD-L1 non-positive received a combination of paclitaxel, 80 mg/m^2, IV infusion on Days 1, 8, and 15 of each 28-day cycle and ipatasertib, 400 mg, PO, QD, from Day 1 to Day 21 of each 28-day cycle and atezolizumab-matching placebo, IV infusion on Day 1 and 15 of each 28-day cycle until loss of clinical benefit, unacceptable toxicity, or withdrawal of consent, whichever occurred first.	Drug: Ipatasertib; Ipatasertib was administered as per the dosage regimen mentioned in arm descriptions.; Drug: Paclitaxel; Paclitaxel was administered as per the dosage regimen mentioned in arm descriptions.; Drug: Placebo for Atezolizumab; Placebo was administered as per the dosage regimen mentioned in arm descriptions.
Experimental: Cohort 1 Arm C: Placebo + Placebo + Paclitaxel; TNBC participants with PD-L1 non-positive received a combination of paclitaxel, 80 mg/m^2, IV infusion on Days 1, 8, and 15 of each 28-day cycle and ipatasertib-matching placebo, PO, QD, from Day 1 to Day 21 of each 28-day cycle and atezolizumab-matching placebo, IV infusion on Day 1 and 15 of each 28-day cycle until loss of clinical benefit, unacceptable toxicity, or withdrawal of consent, whichever occurred first.	Drug: Paclitaxel; Paclitaxel was administered as per the dosage regimen mentioned in arm descriptions.; Drug: Placebo for Atezolizumab; Placebo was administered as per the dosage regimen mentioned in arm descriptions.; Drug: Placebo for Ipatasertib; Placebo was administered as per the dosage regimen mentioned in arm descriptions.
Experimental: Cohort 2 Arm A: Ipatasertib + Atezolizumab + Paclitaxel; TNBC participants with PD-L1 positive received a combination of paclitaxel, 80 mg/m^2, IV infusion on Days 1, 8, and 15 of each 28-day cycle and ipatasertib, 400 mg, PO, QD, from Day 1 to Day 21 of each 28-day cycle and atezolizumab, 840 mg, IV infusion on Day 1 and 15 of each 28-day cycle until loss of clinical benefit, unacceptable toxicity, or withdrawal of consent, whichever occurred first.	Drug: Atezolizumab; Atezolizumab was administered as per the dosage regimen mentioned in arm descriptions.; Drug: Ipatasertib; Ipatasertib was administered as per the dosage regimen mentioned in arm descriptions.; Drug: Paclitaxel; Paclitaxel was administered as per the dosage regimen mentioned in arm descriptions.
Experimental: Cohort 2 Arm B: Placebo+ Atezolizumab + Paclitaxel; TNBC participants with PD-L1 positive received a combination of paclitaxel, 80 mg/m^2, IV infusion on Days 1, 8, and 15 of each 28-day cycle and ipatasertib-matching placebo, PO, QD, from Day 1 to Day 21 of each 28-day cycle and atezolizumab, 840 mg, IV infusion on Day 1 and 15 of each 28-day cycle until loss of clinical benefit, unacceptable toxicity, or withdrawal of consent, whichever occurred first.	Drug: Atezolizumab; Atezolizumab was administered as per the dosage regimen mentioned in arm descriptions.; Drug: Paclitaxel; Paclitaxel was administered as per the dosage regimen mentioned in arm descriptions.; Drug: Placebo for Ipatasertib; Placebo was administered as per the dosage regimen mentioned in arm descriptions.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1	PFS was defined as the time from randomization to the first occurrence of disease progression as determined locally by RECIST or death from any cause during treatment, whichever occurs first.	From Randomization to disease progression, study completion, or death (up to 39 months)
Overall Survival (OS)	OS was defined as the time from randomization to the time of death from any cause on study.	From randomization up to study completion or death (Up to 39 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Adverse Events (AEs)	An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.	Up to 39 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate (ORR)	Defined as the proportion of participants with a complete response (CR) or partial response (PR) on two consecutive occasions >= 4 weeks apart, as determined by the investigator according to RECIST v1.1.	Up to 49 months
Duration of Response (DOR)	Defined as the time from the first occurrence of a documented objective response 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.	Up to 49 months
Clinical Benefit Rate (CBR)	Defined as the proportion of participants who have a CR, PR, or stable disease for >= 24 weeks, as determined by the investigator according to RECIST v1.1.	Up to 49 months
Mean and mean changes from baseline score in participant-reported function (role, physical)	Assessed by EORTC QLC-C30 Selected Scales: Physical Function (Questions 1-5) and Role Function (Questions 6 and 7).	Up to 49 months
Mean and mean changes from baseline score in function in participant-reported Global Health Status (GHS)/Quality of Life (QoL) by assessment timepoint and between treatment arms	Assessed by EORTC QLC-C30 Selected Scale: GHS/QoL (Questions 29 and 30).	Up to 49 months
Progression Free Survival (PFS) for participants with Programmed Death-Ligand 1 (PD-L1)-non-positive tumors	Participants administered with atezolizumab in combination with ipatasertib and paclitaxel (Arm A vs. Arm B in Cohort 1).	Up to 49 months
Overall Survival (OS) for participants with PD-L1-non-positive tumors	Participants administered with atezolizumab in combination with ipatasertib and paclitaxel (Arm A vs. Arm B in Cohort 1).	Up to 49 months
Overall Response Rate (ORR) for participants with PD-L1-non-positive tumors	Participants administered with atezolizumab in combination with ipatasertib and paclitaxel (Arm A vs. Arm B in Cohort 1).	Up to 49 months
Progression Free Survival (PFS) for participants with PIK3CA/AKT1/PTEN-altered tumors	Participants in experimental treatment arm will be compared with participants in control treatment arm.	Up to 49 months
Overall Survival (OS) for participants with PIK3CA/AKT1/PTEN-altered tumors	Participants in experimental treatment arm will be compared with participants in control treatment arm.	Up to 49 months
Overall Response Rate (ORR) for participants with PIK3CA/AKT1/PTEN-altered tumors	Participants in experimental treatment arm will be compared with participants in control treatment arm.	Up to 49 months
Duration of Response (DOR) for participants with PIK3CA/AKT1/PTEN-altered tumors	Participants in experimental treatment arm will be compared with participants in control treatment arm.	Up to 49 months
Plasma concentration of ipatasertib and its metabolite (G037720) (ng/mL) at specified timepoints		Up to 49 months
Serum concentration of atezolizumab (µg/mL) at specified timepoints		Up to 49 months
Level of Anti-Drug Antibodies (ADAs) (%) to Atezolizumab		Up to 49 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): November 25, 2019
• Primary Completion (Actual): February 28, 2023
• Study Completion (Actual): February 28, 2023

Study Registration Dates

• First Submitted: November 7, 2019
• First Submitted That Met QC Criteria: November 22, 2019
• First Posted (Actual): November 26, 2019

Study Record Updates

• Last Update Posted (Actual): March 27, 2024
• Last Update Submitted That Met QC Criteria: February 26, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Neoplasms; Atezolizumab; Antineoplastic Agents; Paclitaxel; Breast Neoplasms; Antibodies, Monoclonal; Tubulin Modulators; Skin Diseases; Ipatasertib; Triple Negative Breast Neoplasms; Neoplasms by Site; Breast Diseases; Antineoplastic Agents, Phytogenic; Antimitotic Agents; Mitosis Modulators
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Triple Negative Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Antineoplastic Agents, Immunological; Protein Kinase Inhibitors; Immune Checkpoint Inhibitors; Paclitaxel; Antibodies, Monoclonal; Atezolizumab; Ipatasertib
• Other Study ID Numbers: CO41101; 2019-000810-12 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

Drug and device information, study documents

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