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

Triple-Negative Breast Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04177108
• Other study ID #: CO41101
• Secondary ID: 2019-000810-12
• Status: Completed
• Phase: Phase 3
• Start date: November 25, 2019
• Est. completion date: February 28, 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 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 242
• Est. completion date: February 28, 2023
• Est. primary completion date: February 28, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Breast Neoplasms
• Triple Negative Breast Neoplasms
• Triple-Negative Breast Cancer

Intervention

Drug:
• Atezolizumab
Atezolizumab was administered as per the dosage regimen mentioned in arm descriptions.
• Ipatasertib
Ipatasertib was administered as per the dosage regimen mentioned in arm descriptions.
• Paclitaxel
Paclitaxel was administered as per the dosage regimen mentioned in arm descriptions.
• Placebo for Atezolizumab
Placebo was administered as per the dosage regimen mentioned in arm descriptions.
• Placebo for Ipatasertib
Placebo was administered as per the dosage regimen mentioned in arm descriptions.

Locations

Country	Name	City	State
Argentina	Fundación CENIT para la Investigación en Neurociencias	Buenos Aires
Argentina	Inst. Angel Roffo; Haematology	Buenos Aires
Argentina	Hospital Britanico	Ciudad Autonoma Bs As
Argentina	Instituto Medico Rio Cuarto	Cordoba
Argentina	Centro Oncologico Riojano Integral (CORI)	La Rioja
Argentina	Fundacion Scherbovsky	Mendoza
Australia	Monash Health Monash Medical Centre	Clayton	Victoria
Australia	Adelaide Cancer Centre	Kurralta Park	South Australia
Australia	Macquarie University Hospital	Macquarie Park	New South Wales
Australia	Peter MacCallum Cancer Centre; Medical Oncology	Melbourne	Victoria
Australia	Mid North Coast Cancer Institute	Port Macquarie	New South Wales
Australia	Sunshine Hospital; Oncology Research	St Albans	Victoria
Australia	Royal North Shore Hospital; Department of Medical Oncology	St Leonards	New South Wales
Australia	St John of God Hospital; Bendat Cancer Centre	Subiaco	Western Australia
Australia	Calvary Mater Newcastle; Medical Oncology	Waratah	New South Wales
Australia	Princess Alexandra Hospital	Woolloongabba	Queensland
Austria	Tiroler Landeskrankenanstalten Ges.M.B.H.; Abt. Für Gynäkologie	Innsbruck
Austria	Ordensklinikum Linz Barmherzige Schwestern; Interne 1 - Hämato-Onkologie	Linz
Austria	Uniklinikum Salzburg, LKH; Univ.Klinik f. Innere Medizin III der PMU	Salzburg
Austria	Medizinische Universität Wien; Univ.Klinik für Innere Medizin I	Wien
Belgium	AZ Maria Middelares	Gent
Belgium	Jessa Zkh (Campus Virga Jesse)	Hasselt
Brazil	Hospital das Clinicas - UFRGS	Porto Alegre	RS
Brazil	Hospital Sao Rafael - HSR	Salvador	BA
Brazil	Clinica de Pesquisa e Centro de Estudos em Oncologia Ginecologica e Mamaria Ltda	Sao Paulo	SP
Brazil	Núcleo de Pesquisa São Camilo; ONCOLOGIA CLINICA / QUIMIOTERAPIA	Sao Paulo	SP
Bulgaria	MHAT Nadezhda	Sofia
Canada	Royal Victoria Hospital	Barrie	Ontario
Canada	Cross Cancer Institute ; Dept of Medical Oncology	Edmonton	Alberta
Canada	McGill University; Glen Site; Oncology	Montreal	Quebec
Canada	Jewish General Hospital; Research Unit	Montréal	Quebec
Canada	The Ottawa Hospital Cancer Centre	Ottawa	Ontario
Canada	Hopital du Saint Sacrement	Quebec City	Quebec
Canada	Fraser Valley Centre British Columbia Cancer Agency	Surrey	British Columbia
Canada	Cancer Care Manitoba	Winnipeg	Manitoba
Colombia	Clinica del Country	Bogota
Colombia	Oncólogos de Occidente	Pereira
Costa Rica	Clinica CIMCA	San José
Czechia	Masaryk?v onkologický ústav; Klinika komplexní onkologické pé?e	Brno
Czechia	Fakultni nemocnice Olomouc; Onkologicka klinika	Olomouc
Denmark	Herlev Hospital; Afdeling for Kræftbehandling	Herlev
Denmark	Odense Universitetshospital, Onkologisk Afdeling R	Odense C
Finland	Docrates Cance Center	Helsinki
Finland	KYS Sadesairaala; Syopatautien poliklinikka	Kuopio
Finland	VAASAN KESKUSSAIRAALA; Onkologian poliklinikka	Vaasa
France	Centre Eugene Marquis; Service d'oncologie	Rennes
Greece	Agioi Anargyroi Cancer Hospital; 2Nd Oncology Dept.	Kifisia
Greece	Euromedical General Clinic of Thessaloniki; Oncology Department	Thessaloniki
Hong Kong	Queen Mary Hospital; Dept of Medicine	Hong Kong
Hong Kong	Tuen Mun Hospital; Clinical Onc	Hong Kong
Hong Kong	Prince of Wales Hospital; Department of Clinical Onocology	Shatin
India	Sahyadri Super Specialty Hospital Hadapsar	Pune	Maharashtra
Israel	Shaare Zedek Medical Center	Jerusalem
Italy	ASST DEGLI SPEDALI CIVILI DI BRESCIA; Oncologia Medica	Brescia	Lombardia
Italy	ASST DI LECCO; Oncologia Medica	Lecco	Lombardia
Italy	Ospedale Civile; Unita Operativa Di Oncologia Medica	Livorno	Toscana
Italy	IRST Istituto Scientifico Romagnolo Per Lo Studio E Cura Dei Tumori, Sede Meldola; Oncologia Medica	Meldola	Emilia-Romagna
Italy	Istituto Nazionale per lo Studio e la Cura dei Tumori Fondazione G. Pascale	Napoli	Campania
Italy	IOV - Istituto Oncologico Veneto - IRCCS; Oncologia Medica II	Padova	Veneto
Italy	IRCCS Istituto Clinico Humanitas; Oncologia	Rozzano (MI)	Lombardia
Italy	ASU FC S. M. DELLA MISERICORDIA; Oncologia	Udine	Friuli-Venezia Giulia
Japan	Aichi Cancer Center Hospital	Aichi
Japan	Fukushima Medical University Hospital	Fukushima
Japan	Gunma Prefectural Cancer Center	Gunma
Japan	Hiroshima University Hospital	Hiroshima
Japan	Kanagawa Cancer Center	Kanagawa
Japan	Kumamoto Shinto General Hospital	Kumamoto
Japan	Okayama University Hospital	Okayama
Japan	Osaka International Cancer Institute	Osaka
Korea, Republic of	Kyungpook National University Medical Center	Daegu
Korea, Republic of	National Cancer Center	Goyang-si
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul St Mary's Hospital	Seoul
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul
Mexico	Health Pharma Professional Research	Cdmx	Mexico CITY (federal District)
Mexico	Investigacion Oncofarmaceutica	La Paz	BAJA California SUR
Mexico	Christus Muguerza Clinica Vidriera	Monterrey	Nuevo LEON
New Zealand	Auckland City Hospital, Cancer and Blood Research	Auckland
New Zealand	Tauranga Hospital, Clinical Trials Unit; BOP Clinical School	Tauranga
New Zealand	Wellington Regional Hospital; Clinical Trials Unit	Wellington
Peru	Centro Medico Monte Carmelo	Arequipa
Peru	Instituto Regional de Enfermedades Neoplasicas	Arequipa
Peru	Clínica San Gabriel; Unidad de Investigación Oncológica de la Clínica San Gabriel	Lima
Peru	Hospital Arzobispo Loayza	Lima
Peru	Instituto Nacional de Enfermedades Neoplasicas	Lima
Peru	Oncosalud Sac; Oncología	Lima
Peru	Unidad de Investigación Oncologica; Hospital Nacional Daniel Alcides Carrion	Lima
Peru	Clinica Ricardo Palma	San Isidro
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; Centr.Diagn.i Lecz.Chor.Piersi	Gliwice
Poland	Szpital Uniwersytecki w Krakowie, Oddzia? Kliniczny Kliniki Onkologii	Kraków
Poland	Wielkopolskie Centrum Onkologii	Poznan
Poland	Narodowy Instytut Onkologii im. M.Sklodowskiej-Curie; Klinika Nowotworow Piersi i Chirurgii Rekonstr	Warszawa
Portugal	Hospital da Luz; Departamento de Oncologia Medica	Lisboa
Portugal	Hospital de Santa Maria; Servico de Oncologia Medica	Lisboa
Portugal	Hospital Beatriz Angelo; Departamento de Oncologia	Loures
Portugal	Centro Hospitalar do Porto ? Hospital de Santo António; Oncologia	Porto
Portugal	IPO do Porto; Servico de Oncologia Medica	Porto
Romania	Oncology Center Sf. Nectarie	Craiova
Russian Federation	Arkhangelsk Regional Clinical Oncology Dispensary	Arkhangelsk	Arhangelsk
Russian Federation	Clinical Oncology Dispensary of Ministry of Health of Tatarstan	Kazan	Tatarstan
Russian Federation	P.A. Gertsen Cancer Research Inst. ; Chemotherapy Dept	Moscow	Moskovskaja Oblast
Russian Federation	University ?linic of headaches	Moscow	Moskovskaja Oblast
Russian Federation	Fed State Budgetary Inst "N.N. Blokhin Med Center of Oncology" MHRF	Moskva	Moskovskaja Oblast
Russian Federation	FSAI Treatment and rehabilitation Centre Ministry of Health; Clinical research and chemotherapy.	Moskva	Moskovskaja Oblast
Russian Federation	SBIH "Moscow Clinical Scientific and Practical Center named after A.S. Loginov of DHM"	Moskva	Moskovskaja Oblast
Russian Federation	Limited Liability Company "RC Medical"	Novosibirsk
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
South Africa	National Hospital; Oncotherapy Dept	Bloemfontein
South Africa	Cancercare	George
South Africa	Wits Clinical Research	Johannesberg
South Africa	Cancercare	Port Elizabeth
South Africa	Wilgers Oncology Centre	Pretoria
Spain	Complejo Hospitalario Universitario A Coruña (CHUAC); Servicio de Oncologia	A Coruña	LA Coruña
Spain	Hospital Clínic i Provincial; Servicio de Hematología y Oncología	Barcelona
Spain	Hospital Provincial de Castellon; Servicio de Oncologia	Castellon de La Plana	Castellon
Spain	Centro Integral Oncologico Clara Campal; Servicio de Oncología	Madrid
Spain	Hospital General Universitario Gregorio Marañon; Servicio de Oncologia	Madrid
Spain	Hospital Ramon y Cajal; Servicio de Oncologia	Madrid
Spain	Hospital Universitario Clínico San Carlos; Servicio de Oncologia	Madrid
Spain	Hospital Universitario Puerta de Hierro; Servicio de Oncologia	Majadahonda	Madrid
Spain	Hospital Clinico Universitario Virgen de la Victoria; Servicio de Oncologia	Malaga
Spain	Hospital Univ Vall d'Hebron; Servicio de Oncologia	Sant Andreu de La Barca	Barcelona
Spain	Hospital Clínico Universitario de Valencia; Servicio de Oncología	Valencia
Switzerland	Universitätsspital Basel	Basel
Switzerland	Universitätsspital Zürich Gynäkologische Klinik; Klinik für Gynäkologie	Zürich
Taiwan	China Medical University Hospital; Surgery	Taichung
Taiwan	National Taiwan Uni Hospital; General Surgery	Taipei
Taiwan	VETERANS GENERAL HOSPITAL; Department of General Surgery	Taipei
Taiwan	Chang Gung Memorial Hosipital at Linkou	Taoyuan City
Thailand	Chulalongkorn Hospital; Medical Oncology	Bangkok
Thailand	Faculty of Med. Siriraj Hosp.; Med.-Div. of Med. Oncology	Bangkok
Thailand	Rajavithi Hospital; Division of Medical Oncology	Bangkok
Thailand	Maharaj Nakorn Chiang Mai Hospital; Department of Surgery/Head Neck and Breast Unit; Clinical Trial	Chiang Mai
Thailand	Khonkaen Hospital	Khonkaen
Thailand	Songklanagarind Hospital; Department of Oncology	Songkhla
Turkey	Memorial Ankara Hastanesi	Ankara
Turkey	Medipol University Medical Faculty; Oncology Department	Istanbul
Turkey	Hacettepe Uni Medical Faculty Hospital; Oncology Dept	Sihhiye/Ankara
Ukraine	Regional Oncology Center; Department of Mammology	Chernigiv
Ukraine	Chemotherapy SI Dnipropetrovsk MA of MOHU	Dnipropetrovsk
Ukraine	SI Institute of general&urgent surgery n/a Zaytseva V.T NAMSU; Purulent Surgery department	Kharkiv	Kharkiv Governorate
Ukraine	ME Kryviy Rih Oncology Dispensary of Dnipropetrovs?k Regional Council; Chemotherapy Department	Kryvyi Rih
Ukraine	MI Kyiv Regional Council Kyiv Regional Oncological Dispensary; Department of Mammology	Kyiv
Ukraine	Municipal Institution Odesa Regional Clinical Hospital	Odesa
Ukraine	RCI Sumy Regional Clinical Oncological Dispensary	Sumy
United Kingdom	BEATSON WEST OF SCOTLAND CANCER CENTRE; Clinical Research Unit ? Level 1	Glasgow
United Kingdom	The Royal Marsden Hospital, Fulham	London
United Kingdom	Nottingham University Hospitals NHS Trust	Nottingham
United States	St. Joseph Mercy Hospital; Cancer Care Center.	Ann Arbor	Michigan
United States	Winship Cancer Institute	Atlanta	Georgia
United States	Medstar Franklin Square Medical Center	Baltimore	Maryland
United States	Mercy Medical Center	Baltimore	Maryland
United States	University of Maryland Medical Center	Baltimore	Maryland
United States	Ochsner Clinic Foundation	Baton Rouge	Louisiana
United States	Charleston Oncology, P .A	Charleston	South Carolina
United States	Rush University	Chicago	Illinois
United States	Kaiser Permanente - Franklin	Denver	Colorado
United States	Henry Ford Health System	Detroit	Michigan
United States	Holy Cross Hospital	Fort Lauderdale	Florida
United States	The West Clinic; West Cancer Center	Germantown	Tennessee
United States	CHI Health Saint Francis; Oncology	Grand Island	Nebraska
United States	Greenville Health System; Cancer Center	Greenville	South Carolina
United States	Hackensack Univ Med Ctr	Hackensack	New Jersey
United States	Memorial Healthcare System - Memorial Regional Hospital	Hollywood	Florida
United States	Jackson Oncology Associates, PLLC	Jackson	Mississippi
United States	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire
United States	UCLA	Los Angeles	California
United States	USA Mitchell Cancer Institute	Mobile	Alabama
United States	Vanderbilt Univ Medical Ctr	Nashville	Tennessee
United States	Ochsner Health System	New Orleans	Louisiana
United States	Memorial Cancer Institute at Memorial West	Pembroke Pines	Florida
United States	Kaiser Permanente - Portland	Portland	Oregon
United States	Oregon Health and Science University	Portland	Oregon
United States	Kaiser Permanente-SCPMG; Oncology Research	San Diego	California
United States	Nancy N. and J.C. Lewis Cancer & Research Pavillion -St. Josephs / Candler Health System-CCD PRIME	Savannah	Georgia
United States	Highlands Oncology Group	Springdale	Arkansas
United States	Stamford Hospital; BCC, MOHR	Stamford	Connecticut
United States	Stanford Cancer Center	Stanford	California
United States	Wake Forest University Baptist Medical Center	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belgium,  Brazil,  Bulgaria,  Canada,  Colombia,  Costa Rica,  Czechia,  Denmark,  Finland,  France,  Greece,  Hong Kong,  India,  Israel,  Italy,  Japan,  Korea, Republic of,  Mexico,  New Zealand,  Peru,  Poland,  Portugal,  Romania,  Russian Federation,  Singapore,  South Africa,  Spain,  Switzerland,  Taiwan,  Thailand,  Turkey,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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	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