A Study of Ipatasertib in Combination With Paclitaxel as a Treatment for Participants With PIK3CA/AKT1/PTEN-Altered, Locally Advanced or Metastatic, Triple-Negative Breast Cancer or Hormone Receptor-Positive, HER2-Negative Breast Cancer

Breast Cancer Clinical Trial

— IPATunity130  

Official title:

A Double-Blind, Placebo-Controlled, Randomized Phase III Study of Ipatasertib in Combination With Paclitaxel as a Treatment for Patients With PIK3CA/AKT1/PTEN-Altered, Locally Advanced or Metastatic, Triple-Negative Breast Cancer or Hormone Receptor-Positive, HER2-Negative Breast Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03337724
• Other study ID #: CO40016
• Secondary ID: 2017-001548-36
• Status: Completed
• Phase: Phase 3
• Start date: January 6, 2018
• Est. completion date: January 4, 2023

Study information

• Verified date: February 2024
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will evaluate the efficacy of ipatasertib + paclitaxel versus placebo + paclitaxel in participants with histologically confirmed, locally advanced or metastatic triple-negative breast cancer (TNBC) and in participants with locally advanced or metastatic hormone receptor positive (HR+)/ human epidermal growth factor receptor 2 negative (HER2-) breast adenocarcinoma who are not suitable for endocrine therapy.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 579
• Est. completion date: January 4, 2023
• Est. primary completion date: January 4, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Women or men aged =>18 years with histologically documented triple-negative breast cancer (TNBC) or HR+/HER2- adenocarcinoma of the breast that is locally advanced or metastatic and is not amenable to resection with curative intent
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
• Adequate hematologic and organ function within 14 days prior to treatment initiation
• Histologically documented TNBC or HR+/HER2- adenocarcinoma of the breast that is locally advanced or metastatic and is not amenable to resection with curative intent
• Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
• Eligible for taxane monotherapy, as per local investigator assessment (e.g., absence of rapid clinical progression, life-threatening visceral metastases, or the need for rapid symptom and/or disease control which may require combination chemotherapy)
• HR+/HER2- breast cancer that is not considered appropriate for endocrine-based therapy and meets one of the following: patient has recurrent disease <=5 years of being on adjuvant endocrine therapy or if patient with de novo metastatic disease have progressed within 6 months of being on first line endocrine therapy.
• Consent to submit a formalin-fixed, paraffin-embedded tumor (FFPE) tissue block or freshly cut unstained, serial tumor slides from the most recently collected tumor tissue for central molecular analysis
• Confirmation of biomarker eligibility using an appropriately validated molecular assay at a diagnostic laboratory, Clinically Laboratory Improvement Amendments (CLIA) or equivalently accredited i.e., valid results from either central testing or local testing of tumor tissue or blood demonstrating PIK3CA/AKT1/PTEN-altered status
• For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception and agreement to refrain from donating eggs
• For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods and agreement to refrain from donating sperm

Exclusion Criteria:

• Treatment with approved or investigational cancer therapy within 14 days prior to treatment initiation
• Any previous chemotherapy for inoperable locally advanced or metastatic TNBC or HR+/HER2- adenocarcinoma of the breast (patients receiving neo/adjuvant chemotherapy eligible provided they have at least a 12 month disease-free interval)
• History of or known presence of brain or spinal cord metastases
• Malignancies other than breast cancer within 5 years prior to treatment initiation (except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or Stage I uterine cancer)
• Prior treatment with an Akt inhibitor (prior PI3K or mTOR inhibitors are allowed)
• History of malabsorption syndrome or other condition that would interfere with enteral absorption or results in the inability or unwillingness to swallow pills
• Active infection requiring systemic anti-microbial treatment (including antibiotics, anti-fungals, and anti-viral agents)
• Known human immunodeficiency virus (HIV) infection
• Known clinically significant history of liver disease consistent with Child-Pugh Class B or C, including active viral or other hepatitis, current drug or alcohol abuse, or cirrhosis
• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to initiation of treatment (or anticipated need during study)
• Pregnant or breastfeeding, or intending to become pregnant during the study
• Clinically significant cardiac dysfunction (including NYHA Class II/III/IV heart failure, left ventricular ejection fraction [LVEF] <50%, active ventricular arrhythmia requiring medication, history of myocardial infarction within 6 months of treatment initiation, clinically significant electrocardiogram [ECG] abnormalities).
• Need for chronic corticosteroid therapy of >=10 mg of prednisone per day or an equivalent dose of other anti-inflammatory corticosteroids or immunosuppressants for a chronic disease
• Unresolved, clinically significant toxicity from prior therapy, except for alopecia and Grade 1 peripheral neuropathy
• Uncontrolled clinical symptoms including pleural effusion, pericardial effusion, or ascites, tumor-related pain, hypercalcemia (or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy)
• History of Type I or Type II diabetes mellitus requiring insulin
• Grade >=2 uncontrolled or untreated hypercholesterolemia or hypertriglyceridemia
• History of or active inflammatory bowel disease or active bowel inflammation
• Clinically significant lung disease (including pneumonitis, interstitial lung disease, idiopathic pulmonary fibrosis, cystic fibrosis, active infection/ history of opportunistic infections)
• Treatment with strong CYP3A inhibitors or strong CYP3A inducers within 2 weeks or 5 drug-elimination half-lives, whichever is longer, prior to initiation of treatment
• Grade >=2 peripheral neuropathy

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms
• Triple Negative Breast Neoplasms

Intervention

Drug:
• Ipatasertib
Ipatasertib, 400 milligrams (mg), administered orally once a day (QD) on Days 1-21 of each 28-day cycle until disease progression, intolerable toxicity, elective withdrawal from the study, or study completion or termination.
• Paclitaxel
Paclitaxel, 80 mg/square meter (m^2), administered intravenously (IV) on Days 1, 8, and 15 of each 28-day cycle until disease progression, intolerable toxicity, elective withdrawal from the study, or study completion or termination.
• Placebo
Matching placebo, administered orally QD on Days 1-21 of each 28-day cycle until disease progression, intolerable toxicity, elective withdrawal from the study, or study completion or termination.

Locations

Country	Name	City	State
Argentina	Fundación CENIT para la Investigación en Neurociencias	Buenos Aires
Argentina	Hosp Provincial D. Centenarios; Oncology Dept	Rosario
Australia	Fiona Stanley Hospital; FSH Cancer Centre Clinical Trials Unit	Bull Creek	Western Australia
Australia	Chris O'Brien Lifehouse	Camperdown	New South Wales
Australia	Cabrini Medical Centre; Oncology	Malvern	Victoria
Australia	Mater Hospital; Cancer Services	South Brisbane	Queensland
Australia	Calvary Mater Newcastle; Medical Oncology	Waratah	New South Wales
Australia	Westmead Hospital; Medical Oncology	Wentworthville	New South Wales
Belgium	Cliniques Universitaires St-Luc	Bruxelles
Belgium	GHdC Site Notre Dame	Charleroi
Belgium	UZ Leuven Gasthuisberg	Leuven
Brazil	Hospital Araujo Jorge; Departamento de Ginecologia E Mama	Goiania	GO
Brazil	Hospital do Câncer de Londrina	Londrina	PR
Brazil	Hospital Nossa Senhora da Conceicao	Porto Alegre	RS
Brazil	Hospital Sao Lucas - PUCRS	Porto Alegre	RS
Brazil	Instituto Nacional de Cancer - INCa; Oncologia	Rio de Janeiro	RJ
Brazil	Santa Casa de Misericordia de Salvador	Salvador	BA
Brazil	Faculdade de Medicina do ABC - FMABC	Santo Andre	SP
Brazil	Hospital Perola Byington	Sao Paulo	SP
Canada	Jewish General Hospital	Montreal	Quebec
Canada	British Columbia Cancer Agency (Bcca) - Vancouver Cancer Centre	Vancouver	British Columbia
Chile	Sociedad de Investigaciones Medicas Ltda (SIM)	Temuco
Costa Rica	Clinica CIMCA	San José
Costa Rica	ICIMED Instituto de Investigación en Ciencias Médicas	San José
Czechia	Masaryk?v onkologický ústav; Klinika komplexní onkologické pé?e	Brno
Czechia	Fakultni nemocnice Olomouc; Onkologicka klinika	Olomouc
France	CHU Besançon - Hôpital Jean Minjoz	Besançon Cedex
France	Polyclinique Bordeaux Nord Aquitaine	Bordeaux
France	Centre Georges Francois Leclerc; Oncologie 3	Dijon
France	ICM; Medecine B3	Montpellier cedex 5
France	Centre Catherine De Sienne	Nantes
France	APHP - Hospital Saint Louis	Paris
France	Institut Jean Godinot; Oncologie Medicale	Reims CEDEX
Germany	Onkologische Schwerpunktpraxis Kurfürstendamm	Berlin
Germany	Praxis für Interdisziplinäre Onkologie und Hämatologie GbR	Freiburg
Germany	Universitätsklinikum Hamburg-Eppendorf; Frauenklinik	Hamburg
Germany	Universitätsklinikum des Saarlandes; Klinik f. Frauenheilkunden und Geburtshilfe	Homburg/Saar
Germany	Praxis Dr.med. Katja Ziegler-Löhr	Köln
Germany	Dres. Andreas Köhler und Roswitha Fuchs	Langen
Germany	Mühlenkreiskliniken; Johannes Wesling Klinikum Minden; Klinik für Frauenheilkunde und Geburtshilfe	Minden
Germany	Oncologianova GmbH - Gesellschaft für Innovationen in der Onkologie	Recklinghausen
Germany	Universitätsfrauen- und Poliklinik am Klinikum Suedstadt	Rostock
Germany	Universitätsklinikum Würzburg; Frauenklinik	Würzburg
Greece	Agioi Anargyroi; 3Rd Dept. of Medical Oncology	Athens
Greece	Anticancer Hospital Ag Savas; 1St Dept of Internal Medicine	Athens
Greece	Euromedical General Clinic of Thessaloniki; Oncology Department	Thessaloniki
Hungary	Orszagos Onkologial Intezet; Onkologiai Osztaly X	Budapest
Hungary	Borsod-Abauj-Zemplen Megyei Korhaz Es Egyetemi Oktato Korhaz; Onkologiai Osztaly	Miskolc
Hungary	Szegedi Tudomanyegyetem, AOK, Szent-Gyorgyi Albert Klinikai Kozpont, Onkoterapias Klinika	Szeged
Hungary	Hetenyi Geza County Hospital; Onkologiai Kozpont	Szolnok
Hungary	Zala County Hospital ICU	Zalaegerszeg
India	Indraprastha Apollo Hospitals	New Delhi	Delhi
India	Rajiv Gandhi Cancer Inst.&Research Center; Medical Oncology	New Delhi	Delhi
Italy	Irccs Centro Di Riferimento Oncologico (CRO); Dipartimento Di Oncologia Medica	Aviano	Friuli-Venezia Giulia
Italy	Ospedale Santa Maria Annunziata; Oncologia	Bagno a Ripoli	Toscana
Italy	Azienda Ospedaliero-Universitaria S.Orsola-Malpighi; Unità Operativa Oncologia Medica	Bologna	Emilia-Romagna
Italy	Istituto Nazionale Tumori Irccs Fondazione g. PASCALE;U.O.C. Oncologia Medica Senologica	Napoli	Campania
Italy	IOV - Istituto Oncologico Veneto - IRCCS; Oncologia Medica II	Padova	Veneto
Japan	Aichi Cancer Center Hospital	Aichi
Japan	National Cancer Center Hospital East	Chiba
Japan	National Hospital Organization Kyushu Cancer Center;Breast Oncology	Fukuoka
Japan	Fukushima Medical University Hospital	Fukushima
Japan	Hyogo Medical University Hospital	Hyogo
Japan	Kanagawa Cancer Center	Kanagawa
Japan	St. Marianna University Hospital	Kanagawa
Japan	Tokai University Hospital	Kanagawa
Japan	Kumamoto Shinto General Hospital	Kumamoto
Japan	Niigata Cancer Center Hospital	Niigata
Japan	Okayama University Hospital	Okayama
Japan	Kinki University Hospital, Faculty of Medicine; Surgery	Osaka
Japan	National Hospital Organization Osaka National Hospital	Osaka
Japan	Saitama Cancer Center, Breast Oncology	Saitama
Japan	Shizuoka Cancer Center	Shizuoka
Japan	National Cancer Center Hospital	Tokyo
Japan	Showa University Hospital; Breast Surgery	Tokyo
Japan	St. Luke's International Hospital	Tokyo
Japan	The Cancer Institute Hospital of JFCR	Tokyo
Korea, Republic of	National Cancer Center	Goyang-si
Korea, Republic of	Inha University Hospital	Incheon
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam-si
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul
Mexico	Centro Medico Dalinde	Cdmx	Mexico CITY (federal District)
Mexico	Merida | Investigacion Clinica	Mérida	Yucatan
Mexico	CENEIT Oncologicos; DENTRO DE CONDOMINIO SAN FRANCISCO	Mexico City
Mexico	Centro Médico Zambrano Hellion	Monterrey	Nuevo LEON
North Macedonia	Clinical Hospital; Oncology Department	Bitola
North Macedonia	PHI University Clinic of Radiotherapy and Oncology; Breast malignancy	Skopje
North Macedonia	PHI University Clinic of Radiotherapy and Oncology; Malignant diseases of thorax	Skopje
Peru	Centro Medico Monte Carmelo	Arequipa
Peru	Hospital Daniel Alcides Carrion	Callao
Peru	Clínica San Gabriel; Unidad de Investigación Oncológica de la Clínica San Gabriel	Lima
Peru	Hospital Nacional Cayetano Heredia; Ocología; Servicio de Hematología Oncología Médica	Lima
Peru	Instituto Nacional de Enfermedades Neoplasicas	Lima
Peru	Oncosalud Sac; Oncología	Lima
Peru	Clinica Ricardo Palma	San Isidro
Peru	Instituto Regional de Enfermedades Neoplasicas - IREN Norte	Trujillo
Poland	Instyt. Centrum Zdrowia Matki Polki; Klinika Chirurgii Onk. Chorób Piersi z Podod. Onko Klinicznej	?ód?
Poland	Narodowy Inst.Onkol.im.Sklodowskiej-Curie Panstw.Inst.Bad Gliwice; III Klin. Radioter. i Chemioter.	Gliwice
Poland	Narodowy Instytut Onkologii im. M.Sklodowskiej-Curie; Klinika Nowotworow Piersi i Chirurgii Rekonstr	Warszawa
Russian Federation	Arkhangelsk Regional Clinical Oncology Dispensary	Arkhangelsk	Arhangelsk
Russian Federation	Ivanovo Regional Oncology Dispensary	Ivanovo
Russian Federation	SBIH Kaluga Region Clinical Oncology Dispensary	Kaluga
Russian Federation	Clinical Oncology Dispensary of Ministry of Health of Tatarstan	Kazan	Tatarstan
Russian Federation	Moscow City Oncology Hospital #62	Moscovskaya Oblast	Moskovskaja Oblast
Russian Federation	Federal State Institution, Moscow Research Oncology Institute n.a. P.A. Hertzen; Oncourology	Moscow	Moskovskaja Oblast
Russian Federation	Blokhin Cancer Research Center; Combined Treatment	Moskva	Moskovskaja Oblast
Russian Federation	FSI Rostov research oncological institute of MoH and SD of RF; PAD	Rostov-on-Don	Rostov
Russian Federation	S-Pb clinical scientific practical center of specialized kinds of medical care (oncological)	Saint-Petersburg	Sankt Petersburg
Singapore	National Cancer Centre; Medical Oncology	Singapore
Singapore	National University Hospital; National University Cancer Institute, Singapore (NCIS)	Singapore
Slovenia	Institute of Oncology Ljubljana	Ljubljana
South Africa	Medical Oncology Centre of Rosebank; Oncology	Johannesburg
Spain	Hospital Clinic Barcelona; Servicio de oncologia	Barcelona
Spain	Hospital del Mar; Servicio de Oncologia	Barcelona
Spain	Vall d?Hebron Institute of Oncology (VHIO), Barcelona	Barcelona
Spain	Hospital Provincial de Castellon; Servicio de Oncologia	Castellon de La Plana	Castellon
Spain	Hospital Universitario Reina Sofia; Servicio de Oncologia	Córdoba	Cordoba
Spain	Hospital de Donostia; Servicio de Oncologia	Guipuzcoa
Spain	HOSPITAL DE MADRID NORTE SANCHINARRO- CENTRO INTEGRAL ONCOLOGICO CLARA CAMPAL; Servicio de Oncologia	Madrid
Spain	Hospital Ramon y Cajal; Servicio de Oncologia	Madrid
Spain	Hospital Universitario Puerta de Hierro; Servicio de Oncologia	Majadahonda	Madrid
Spain	Complejo Hospitalario Universitario de Santiago (CHUS) ; Servicio de Oncologia	Santiago de Compostela	LA Coruña
Spain	Hospital Universitario Virgen del Rocio; Servicio de Oncologia	Sevilla
Spain	Hospital Clinico Universitario; Oncologia	Valencia
Taiwan	Chi Mei Medical Center Liou Ying Campus	Liuying Township
Taiwan	National Taiwan Uni Hospital; General Surgery	Taipei
Taiwan	VETERANS GENERAL HOSPITAL; Department of General Surgery	Taipei
Taiwan	Koo Foundation Sun Yat-Sen Cancer Center; Hemato-Oncology	Taipei City
Turkey	Ankara Bilkent City Hospital	Ankara
Turkey	Dicle Uni Medical Faculty; Internal Medicine	Diyarbakir
Turkey	Medipol University Medical Faculty; Oncology Department	Istanbul
Turkey	Prof. Dr. Cemil Tascioglu City Hospital; Med Onc	Istanbul
Turkey	Katip Celebi University Ataturk Training and Research Hospital; Oncology	Izmir
Turkey	Sakarya University Medical School; Medical Oncology	Sakarya
Ukraine	Chemotherapy SI Dnipropetrovsk MA of MOHU	Dnipropetrovsk
Ukraine	Kyiv City Clinical Oncological Center, Day Hospital Department for Oncological patients	Kiev
Ukraine	National Cancer Institute MOH of Ukraine	Kiev
Ukraine	Lviv State Oncological Regional Treatment and Diagnostic Center	Lviv
United Kingdom	Velindre Cancer Centre	Cardiff
United Kingdom	University Hospital coventry; Oncology Department	Coventry
United Kingdom	The Beatson West of Scotland Cancer Centre; Cancer Clinical Trials Unit	Glasgow
United Kingdom	Royal Marsden Hospital - London	London
United Kingdom	Derriford Hospital	Plymouth
United Kingdom	Royal Stoke University Hospital	Stoke-on-Trent
United Kingdom	Royal Marsden Hospital; Dept of Medical Oncology	Sutton
United States	Johns Hopkins Sidney Kimmel Comprehensive Cancer Center	Baltimore	Maryland
United States	Mercy Medical Center	Baltimore	Maryland
United States	University of Maryland	Baltimore	Maryland
United States	Texas Oncology, P.A.	Dallas	Texas
United States	UT Southwestern Medical Center; Simmons Comprehensive Cancer Center, Simmons Pharmacy	Dallas	Texas
United States	West Clinic	Germantown	Tennessee
United States	Memorial Sloan Kettering Cancer Center at Westchester	Harrison	New York
United States	Memorial Regional Hospital	Hollywood	Florida
United States	Oncology Consultants PA	Houston	Texas
United States	UCSD Moores Cancer Center	La Jolla	California
United States	USC Norris Cancer Center	Los Angeles	California
United States	Mount Sinai Comprehensive Cancer Center	Miami Beach	Florida
United States	Memorial Sloan Kettering	New York	New York
United States	USC Norris Cancer Center; USC Oncology Hematology Newport Beach	Newport Beach	California
United States	Kaiser Permanente - Oakland	Oakland	California
United States	UF Health Cancer Center at Orlando Health	Orlando	Florida
United States	Memorial Hospital West	Pembroke Pines	Florida
United States	Kaiser Permanente - Roseville	Roseville	California
United States	Kaiser Permanente Sacramento Medical Center	Sacramento	California
United States	UC Davis; Comprehensive Cancer Center	Sacramento	California
United States	Kaiser Permanente - San Francisco (2238 Geary)	San Francisco	California
United States	UCSF Comprehensive Cancer Ctr	San Francisco	California
United States	K. Permanente - San Jose	San Jose	California
United States	Kaiser Permanente - San Leandro	San Leandro	California
United States	K. Permanente - Santa Clara	Santa Clara	California
United States	Kaiser Permanente - South San Francisco	South San Francisco	California
United States	Kaiser Permanente - Vallejo	Vallejo	California
United States	K. Permanente - Walnut Creek	Walnut Creek	California

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Belgium,  Brazil,  Canada,  Chile,  Costa Rica,  Czechia,  France,  Germany,  Greece,  Hungary,  India,  Italy,  Japan,  Korea, Republic of,  Mexico,  North Macedonia,  Peru,  Poland,  Russian Federation,  Singapore,  Slovenia,  South Africa,  Spain,  Taiwan,  Turkey,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cohort A: Progression-Free Survival (PFS)	PFS was defined as the time from randomization to the first occurrence of disease progression, as determined locally by the investigator through the use of Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v.1.1), or death from any cause, whichever occurred first, assessed up to 27 months for this outcome measure. 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 on 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.	From randomization up to 27 months
Primary	Cohort B: PFS	PFS was defined as the time from randomization to the first occurrence of disease progression, as determined locally by the investigator through the use of RECIST v.1.1, or death from any cause, whichever occurred first, assessed up to 24.4 months for this outcome measure. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on 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 was also considered progression. Abbreviation used in statistical analysis: PI3K=phosphoinositide 3-kinase and mTOR=mammalian target of rapamycin inhibitor.	From randomization up to 24.4 months
Primary	Cohort C: PFS	PFS for Cohort C was defined as the time from enrollment to the first occurrence of disease progression, as determined locally by the investigator through the use of RECIST v.1.1, or death from any cause, whichever occurred first, assessed up to 31 months for this outcome measure. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on 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 was also considered progression.	From enrollment up to 31 months
Secondary	Cohort A and B: Objective Response Rate (ORR)	ORR was defined as percentage of participants with partial response (PR) or complete response (CR) on 2 consecutive occasions =4 weeks apart as determined by the investigator using RECIST v.1.1, assessed up to 27 months for Cohort A and up to 24.4 months for Cohort B, for this outcome measure. CR was 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 was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. Percentages are rounded off to the nearest decimal point.	From randomization up to 27 months for Cohort A and up to 24.4 months for Cohort B
Secondary	Cohort C: ORR	ORR was defined as percentage of participants with PR or CR on 2 consecutive occasions =4 weeks apart as determined by the investigator using RECIST v.1.1, assessed up to 31 months for this outcome measure. CR was 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 was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. Percentages are rounded off to the nearest decimal point.	From enrollment up to 31 months
Secondary	Cohort A and B: Duration of Response (DOR)	DOR was defined as the time from the first occurrence of a documented OR (CR or PR) to PD, as determined locally by the investigator through the use of RECIST v1.1, or death from any cause, whichever occurred first assessed up to 27 months for Cohort A and up to 24.4 months for Cohort B, for this outcome measure. CR was 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 was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on 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 was also considered progression.	From randomization up to 27 months for Cohort A and up to 24.4 months for Cohort B
Secondary	Cohort C: DOR	DOR was defined as the time from the first occurrence of a documented OR (CR or PR) to PD, as determined locally by the investigator through the use of RECIST v1.1, or death from any cause, whichever occurred first, assessed up to 31 months for this outcome measure. CR was 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 was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on 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 was also considered progression.	From enrollment up to 31 months
Secondary	Cohort A and B: Clinical Benefit Rate (CBR)	CBR was defined as percentage of participants with an objective response (CR or PR), or stable disease (SD) for at least 24 weeks, as determined by the investigator through the use of RECIST v.1.1. assessed up to From randomization up to 27 months for Cohort A and up to 24.4 months for Cohort B for this outcome measure. CR was 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 was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. Percentages are rounded off to the nearest decimal point.	From randomization up to 27 months for Cohort A and up to 24.4 months for Cohort B
Secondary	Cohort C: CBR	CBR was defined as percentage of participants with an objective response (CR or PR), or SD for at least 24 weeks, as determined by the investigator through the use of RECIST v.1.1 assessed up to 31 months for this outcome measure. CR was 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 was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. Percentages are rounded off to the nearest decimal point.	From enrollment up to 31 months
Secondary	Overall Survival (OS)	OS was defined as the time from randomization to death from any cause.	From randomization/ enrollment (Cohort C) up to death from any cause, up to 45 months for Cohort A, up to 46 months for Cohort B and up to 31 months for Cohort C
Secondary	Cohort A and B: Change From Baseline in Global Health Status (GHS)/Health-Related Quality of Life (HRQoL) Score Measured by GHS/HRQoL Scale (Questions 29 and 30) of the EORTC QLQ-C30	European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) is a cancer-specific instrument with 30 questions covering symptoms, functioning, and health-related quality of life (HRQoL). The participant's assessment of overall HRQoL is assessed by using the last 2 questions (29 and 30) of the instrument, with each of these items based on a 7-point scale (1=very poor to 7=excellent), which are then combined into the GHS/QoL multi-item scale. The scores obtained for each question were averaged into a raw score for the scale, and this raw score for the scale was then subsequently linearly transformed to a scale score of 0 to 100, with a high score indicating better GHS/QoL. Negative change from Baseline values in the GHS/QoL change from baseline analysis indicated deterioration in HRQoL and positive values indicated improvement.	Baseline, Day 1 of Cycles 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23 and 24 (cycle length=28 days)
Secondary	Cohort C: Change From Baseline in GHS/HRQoL Score Measured by GHS/HRQoL Scale (Questions 29 and 30) of the EORTC QLQ-C30	EORTC QLQ-C30 is a cancer-specific instrument with 30 questions covering symptoms, functioning, and health-related quality of life (HRQoL). The participant's assessment of overall HRQoL is assessed by using the last 2 questions (29 and 30) of the instrument, with each of these items based on a 7-point scale (1=very poor to 7=excellent), which are then combined into the GHS/QoL multi-item scale. The scores obtained for each question were averaged into a raw score for the scale, and this raw score for the scale was then subsequently linearly transformed to a scale score of 0 to 100, with a high score indicating better GHS/QoL. Negative change from Baseline values in the GHS/QoL change from baseline analysis indicated deterioration in HRQoL and positive values indicated improvement.	Baseline, Day 1 of Cycles 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, and 44 (cycle length=28 days)
Secondary	Cohort B: Time to Deterioration (TTD) in Pain	Time to deterioration in GHS/HRQoL was defined as the time from randomization to first observed = 11-point increase from Baseline in pain scale score (Question 9 and 19) in EORTC QLQ-C30 linearly transformed GHS/HRQoL scale score, assessed up 24.4 months for this outcome measure. TTD was planned to be assessed only in cohort with HR+/HER2 - breast cancer participants (Cohort B). Questions 9 and 19 that assessed pain, used 4-point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much). The scores were linearly transformed on a scale of 0 to 100, with higher scores indicating increased severity in symptoms.	Baseline up to 24.4 months
Secondary	Number of Participants With Adverse Events (AEs)	An AE is any untoward medical occurrence in a participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. AEs were reported based on the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 4.0.	Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
Secondary	Number of Participants With at Least One Adverse Events of Special Interest (AESI)	An AE is any untoward medical occurrence in a participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. AEs were reported based on the NCI CTCAE, Version 4.0. AESI include cases of potential drug-induced liver injury that include an elevated alanine aminotransferase (ALT) or aspartate aminotransferase (AST) in combination with either an elevated bilirubin or clinical jaundice, as defined by Hy's Law. Suspected transmission of an infectious agent by the study drug, Grade >= 3 fasting hyperglycemia, hepatotoxicity, diarrhea, rash, ALT/AST elevations. Grade >= 2 colitis/enterocolitis.	Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C
Secondary	Cohorts A and B:Plasma Concentration of Ipatasertib		Days 1 and 15 of Cycle 1: 1 to 3 hours post dose, and on Day 15 of Cycle 3: 2 to 4 hours post dose (cycle length= 28 days)
Secondary	Cohort C: Plasma Concentration of Ipatasertib		Days 1 and 15 of Cycle 1: 1 to 3 hours post dose, and on Day 15 of Cycle 3: 2 to 4 hours post dose (cycle length= 28 days)
Secondary	Cohorts A and B: Plasma Concentration of G-037720	G-037720 was a metabolite of ipatasertib.	Days 1 and 15 of Cycle 1: 1 to 3 hours post dose, and on Day 15 of Cycle 3: 2 to 4 hours post dose (cycle length= 28 days )
Secondary	Cohort C: Plasma Concentration of G-037720	G-037720 was a metabolite of ipatasertib.	Days 1 and 15 of Cycle 1: 1 to 3 hours post dose, and on Day 15 of Cycle 3: 2 to 4 hours post dose (cycle length= 28 days )
Secondary	Cohort C: 1-year Event-free PFS Rate	PFS was defined as the time from enrollment to the first occurrence of disease progression, as determined locally by the investigator through the use of RECIST v.1.1, or death from any cause, whichever occurred first. Event-free PFS rate was defined as percentage of participants who did not experience any event and survived at 1 year after enrollment. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on 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 was also considered progression. Percentages are rounded off to the nearest decimal point. As prespecified in the protocol, this outcome measure was applicable only to Cohort C.	From enrollment until the occurrence of disease progression or death from any cause, whichever occurred earlier, up to 1 year
Secondary	Cohort C: 1-year Event-free OS Rate	OS was defined as the time from enrollment to death from any cause. Event-free OS rate was defined as percentage of participants who did not experience any event and survived at 1 year after enrollment. As prespecified in the protocol, this outcome measure was applicable only to Cohort C. Percentages were rounded off to the nearest decimal.	From enrollment up to death from any cause, up to 1 year
Secondary	Cohort C: Serum Concentration of Atezolizumab	As prespecified in the protocol, this outcome measure was applicable only to Cohort C.	Day 1 of Cycle 1: 30 minutes post dose, predose on Day 15 of Cycle 1 and predose on Day 1 of Cycles 2, 3, 4, 8, 12 and 16 (cycle length=28 days)
Secondary	Cohort C: Number of Participants With Anti-Drug Antibodies (ADAs) to Atezolizumab	The numbers of ADA-positive participants after drug administration were summarized for participants exposed to atezolizumab. As prespecified in the protocol, this outcome measure was applicable only to Cohort C.	Up to 45.5 months