A Study of Atezolizumab in Locally Advanced or Metastatic Urothelial or Non-Urothelial Carcinoma of the Urinary Tract

Urinary Tract Cancer Clinical Trial

Official title:

An Open Label, Single Arm, Multicenter, Safety Study of Atezolizumab in Locally Advanced or Metastatic Urothelial or Non-Urothelial Carcinoma of the Urinary Tract

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02928406
• Other study ID #: MO29983
• Secondary ID: 2016-002625-11
• Status: Completed
• Phase: Phase 3
• Start date: November 30, 2016
• Est. completion date: December 12, 2022

Study information

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

Clinical Trial Summary

This Phase IIIb, multicenter study will assess the safety of atezolizumab as second- to fourth-line treatment for participants with locally advanced or metastatic urothelial or non-urothelial cancer of the urinary tract in addition to evaluate the efficacy of atezolizumab and potential tumor biomarkers associated with atezolizumab.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1004
• Est. completion date: December 12, 2022
• Est. primary completion date: December 12, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Participants with histologically documented locally advanced (tumor [T] 4b, any node [N]; or any T, N 2-3) or metastatic (M1, Stage IV) urothelial or non-urothelial carcinoma of the urinary tract
• Participants with measurable and/or non-measurable disease according to RECIST v1.1
• Participants must have progressed during or following treatment with at least one prior (and not more than 3) treatments for inoperable, locally advanced or metastatic urothelial or non-urothelial carcinoma of the urinary tract
• If available, a representative formalin-fixed paraffin-embedded (FFPE) tumor specimen block should be submitted
• Eastern cooperative oncology group (ECOG) performance status 0, 1 or 2

Exclusion Criteria:

• Treatment with more than three prior lines of systemic therapy for inoperable, locally advanced or metastatic urothelial or non-urothelial carcinoma of the urinary tract
• Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 4 weeks prior to study treatment initiation

1. Participants who were in another clinical trial with therapeutic intent within 4 weeks of study treatment initiation but were not on active drug in that prior trial are eligible

2. Participants who were in another clinical trial with therapeutic intent within 4 weeks of study treatment initiation but were in the follow-up phase of that prior trial and had stopped receiving active drug 4 or more weeks before study treatment initiation are eligible

• Malignancies other than the one studied in this protocol within 5 years prior to Cycle 1, Day 1
• Evidence of significant uncontrolled concomitant disease that could affect compliance with the protocol
• Significant renal disorder indicating a need for renal transplant

Related Conditions & MeSH terms

• Urinary Tract Cancer
• Urologic Neoplasms

Intervention

Drug:
• Atezolizumab
Atezolizumab 1200 milligrams (mg) will be administered by intravenous (IV) infusion Q3W.

Locations

Country	Name	City	State
Argentina	Inst. Alexander Fleming; Oncologia	Buenos Aires
Argentina	Hospital Aleman	Caba
Argentina	Hospital Britanico de Buenos Aires	Ciudad Autonoma Buenos Aires
Australia	Royal Adelaide Hospital	Adelaide	South Australia
Australia	Box Hill Hospital	Box Hill	Victoria
Australia	Canberra Hospital; Medical Oncology	Canberra	Australian Capital Territory
Australia	Austin Hospital Olivia Newton John Cancer Centre	Heidelberg	Victoria
Australia	Royal Hobart Hospital; Hematology/Oncology	Hobart	Tasmania
Australia	Macquarie University Hospital	Macquarie Park	New South Wales
Australia	Prince of Wales Hospital; Oncology	Randwick	New South Wales
Australia	Icon Cancer Foundation	South Brisbane	Queensland
Australia	Northern Cancer Institute	St Leonards	New South Wales
Australia	Calvary Mater Newcastle; Medical Oncology	Waratah	New South Wales
Austria	Medizinische Universität Innsbruck; Universitätsklinik für Urologie	Innsbruck
Austria	Ordensklinikum Linz Elisabethinen; Abteilung für Urologie und Andrologie	Linz
Austria	Landeskrankenhaus Salzburg; Universitätsklinik für Urologie und Andrologie der PMU	Salzburg
Austria	Medizinische Universität Wien; Univ.Klinik für Innere Medizin I - Abt. für Onkologie	Wien
Austria	Medizinische Universität Wien; Universitätsklinik für Urologie	Wien
Belgium	UZ Brussel	Brussel
Belgium	Cliniques Universitaires St-Luc	Bruxelles
Belgium	UZ Leuven Gasthuisberg	Leuven
Belgium	CHU Sart-Tilman	Liège
Brazil	Hospital de Cancer de Barretos	Barretos	SP
Brazil	Centro Integrado de Oncologia de Curitiba	Curitiba	PR
Brazil	Pronutrir - suporte nutricional e quimioterapia ltda.	Fortaleza	CE
Brazil	Hospital Sao Lucas - PUCRS	Porto Alegre	RS
Brazil	Hospital Alemao Oswaldo Cruz	Sao Paulo	SP
Brazil	Hospital Sírio-Libanês	Sao Paulo	SP
Bulgaria	Complex Oncology Center (COC)-Plovidiv	Plovdiv
Bulgaria	SHATOD - Sofia	Sofia
Bulgaria	University Multiprofile Hospital for Active Treatment Tsaritsa Yoanna - ISUL EAD	Sofia
Canada	Royal Victoria Hospital	Barrie	Ontario
Canada	Tom Baker Cancer Centre-Calgary	Calgary	Alberta
Canada	Cross Cancer Institute ; Dept of Medical Oncology	Edmonton	Alberta
Canada	Queen Elizabeth II Health Sciences Centre	Halifax	Nova Scotia
Canada	The Ottawa Hospital Cancer Center; General Campus	Ottawa	Ontario
China	Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School	Nanjing City
Colombia	Clinica del Country	Bogota
Croatia	Clinical Hospital Centre Zagreb	Zagreb
Czechia	Fakultni nemocnice u sv. Anny v Brne	Brno
Czechia	Fakultni nemocnice Kralovske Vinohrady	Praha
Czechia	Fakultni Thomayerova Nemocnice; Onkologicke Oddeleni	Praha
Denmark	Aalborg Universitetshospital; Onkologisk Afdeling	Aalborg
Denmark	Aarhus Universitetshospital; Kræftafdelingen	Aarhus N
Denmark	Herlev Hospital; Afdeling for Kræftbehandling	Herlev
Denmark	Rigshospitalet; Onkologisk Klinik	København Ø
Estonia	East Tallinn Central Hospital; Clinic of Internal Medicine	Tallinn
Estonia	North Estonia Medical Centre Foundation; Oncology Center	Tallinn
Germany	Universitätsklinikum "Carl Gustav Carus"; Klinik und Poliklinik für Urologie	Dresden
Germany	Universitätsklinikum Erlangen; Medizinische Klinik 5 - Hämatound Internist Onko	Erlangen
Germany	Universitätsmedizin Göttingen Georg-August-Universität; Klinik für Urologie	Göttingen
Germany	Krankenhaus Martha-Maria Halle-Dölau, Klinik für Urologie	Halle (Saale)
Germany	Medizinische Hochschule Hannover; Klinik für Urologie und Onkologische Urologie	Hannover
Germany	Onkologische Schwerpunktpraxis	Heidelberg
Germany	Universitätsklinikum Schleswig-Holstein / Campus Lübeck; Klinik für Urologie	Lübeck
Germany	Kliniken Maria Hilf GmbH, Krankenhaus St. Franziskus	Mönchengladbach
Germany	Klinikum rechts der Isar der TU München; Urologische Klinik und Poliklinik	München
Germany	Universitätsklinikum Münster, Klinik für Urologie und Kinderurologie	Münster
Germany	Universitätsklinikum Tübingen; Klinik für Urologie	Tübingen
Germany	Universitätsklinikum Ulm; Klinik für Urologie	Ulm
Greece	Alexandras General Hospital of Athens; Oncology Department	Athens
Greece	IASO General Hospital of Athens	Athens
Greece	Agioi Anargyroi Cancer Hospital; 2Nd Oncology Dept.	Kifisia
Greece	Metropolitan Hospital; 2Nd Oncology Clinic	Piraeus
Greece	Thermi Clinic; Oncology Clinic	Thermi Thessalonikis
Greece	Euromedical General Clinic of Thessaloniki; Oncology Department	Thessaloniki
Greece	Papageorgiou General Hospital; Medical Oncology	Thessaloniki
Hungary	Honvédelmi Minisztérium Állami Egészségügyi Központ; Onkológiai Osztály; Oncology department	Budapest
Hungary	Orszagos Onkologiai Intezet	Budapest
Hungary	Semmelwies University of Medicine; Urology Dept.	Budapest
Hungary	Szegedi Tudomanyegyetem, AOK, Szent-Gyorgyi Albert Klinikai Kozpont, Onkoterapias Klinika	Szeged
Hungary	Jász-Nagykun-Szolnok Megyei Hetényi Géza Kórház; Onkológiai Osztály	Szolnok
India	HealthCare Global Cancer Centre; Medical Oncology	Ahmedabad	Gujarat
India	Artemis Health Institute	Gurgaon	Haryana
India	TATA Medical Centre; Medical Oncology	Kolkata	WEST Bengal
India	Max Super Speciality Hospital	New Delhi	Delhi
Ireland	Cork University Hospital	Cork
Ireland	Adelaide & Meath Hospital, Dublin, Incorporating the National Children's Hospital; Oncology Day Unit	Dublin
Italy	Azienda USL8 Arezzo-Presidio Ospedaliero 1 San Donato;U.O.C. Oncologia	Arezzo	Toscana
Italy	Irccs Ist. Tumori Giovanni Paolo Ii; Dipartimento Oncologia Medica	Bari	Puglia
Italy	Asst Papa Giovanni XXIII; Oncologia Medica	Bergamo	Lombardia
Italy	AZ.Osp S. Orsola ? Malpighi-Reparto di Oncologia Medica	Bologna	Emilia-Romagna
Italy	A.O.U. Cagliari-P.O. Monserrato;U.O. Oncologia	Cagliari	Sardegna
Italy	Ospedale Cannizzaro, Oncologia	Catania	Sicilia
Italy	Policlinico Ospedaliero Ss Annunziata; U.O. Di Clinica Oncologica	Chieti	Abruzzo
Italy	ASST DI CREMONA; Dip. Medicina - S.C. Oncologia	Cremona	Lombardia
Italy	IRCCS Istituto Nazionale Per La Ricerca Sul Cancro (IST); Oncologia Medica A	Genova	Liguria
Italy	IRST Istituto Scientifico Romagnolo Per Lo Studio E Cura Dei Tumori, Sede Meldola; Oncologia Medica	Meldola	Emilia-Romagna
Italy	Irccs Istituto Nazionale Dei Tumori (Int);S.C. Medicina Oncologica 2	Milano	Lombardia
Italy	Istituto Europeo Di Oncologia	Milano	Lombardia
Italy	A.O. Universitaria Policlinico Di Modena; Oncologia	Modena	Emilia-Romagna
Italy	Azienda Ospedaliera Universitaria Federico II	Napoli	Campania
Italy	ISTITUTO NAZIONALE TUMORI IRCCS FONDAZIONE G. PASCALE; Dipartimento Uro-Ginecologico	Napoli	Campania
Italy	A.O. UNIVERSITARIA S. LUIGI GONZAGA; Oncologia Medica	Orbassano	Piemonte
Italy	IRCCS Istituto Oncologico Veneto (IOV); Oncologia Medica Prima	Padova	Veneto
Italy	Azlenda Ospendaliero-Universitaria Pisana; C.O. Oncologia 2	Pisa	Toscana
Italy	Arcispedale Santa Maria Nuova; Oncologia	Reggio Emilia	Emilia-Romagna
Italy	Azienda Ospedaliera San Camillo Forlanini; Oncologia Medica	Roma	Lazio
Italy	Policlinico Universitario "Agostino Gemelli"; U.O.C. Oncologia Medica	Roma	Lazio
Italy	Policlinico Universitario Campus Biomedico Di Roma; U.O.Oncologia Medica	Roma	Lazio
Italy	IRCCS Ospedale Casa Sollievo Della Sofferenza; Oncologia	San Giovanni Rotondo	Puglia
Italy	Azienda Ospedaliera S. Maria - Terni; Oncologia	Terni	Umbria
Italy	A.O. Universitaria S. Maria Della Misericordia Di Udine; Oncologia	Udine	Friuli-Venezia Giulia
Italy	Azienda Ospedaliera di Verona-Policlinico G.B. Rossi; Oncologia Medica	Verona	Veneto
Lebanon	Hotel Dieu de France; Oncology	Beirut
Lithuania	Hospital of Lithuanian University of Health Sciences Kaunas Clinics - Endocrinology clinic	Kaunas
Lithuania	National Cancer Institute	Vilnius
Netherlands	NKI/AvL	Amsterdam
Netherlands	VU MEDISCH CENTRUM; Dept. of Medical Oncology	Amsterdam
Netherlands	Academ Ziekenhuis Groningen; Medical Oncology	Groningen
Netherlands	Maastricht University Medical Centre; Medical Oncology	Maastricht
Netherlands	St. Antonius locatie Leidsche Rijn	Utrecht
Poland	NZOZ Onko-Dent G. L. Slomian, Spolka Jawna	?ory
Poland	Centrum Onkologii Ziemi LUBELSKIEJ im. Sw Jana z Dukli, I oddz. Chemioterapii	Lublin
Poland	Szpital Kliniczny Przemienienia Pa?skiego Uniwersytetu Medycznego im. Karola Marcinkowskiego	Poznan
Poland	Szpital Grochowski im. dr med. Rafa?a Masztaka Sp. z o.o.	Warszawa
Portugal	Hospital de Braga; Servico de Oncologia Medica X	Braga
Portugal	HUC; Servico de Urologia e Transplantacao Renal	Coimbra
Portugal	Hospital de Santa Maria; Servico de Oncologia Medica	Lisboa
Portugal	IPO do Porto; Servico de Oncologia Medica	Porto
Romania	Oncopremium Team Srl	Baia Mare
Romania	Institutul Oncologic Prof. Dr. Ion Chiricuta Cluj-Napoca; Spital de zi-Parter	Cluj-Napoca
Romania	Centrul de Oncologie Sfantul Nectarie	Craiova
Romania	Centrul de Radioterapie AMETHYST	Floresti
Romania	Oncomed SRL; Oncologie	Timisoara
Russian Federation	Blokhin Cancer Research Center; Urological Dept	Moscow	Moskovskaja Oblast
Russian Federation	P.A. Herzen Oncological Inst. ; Oncology	Moscow	Moskovskaja Oblast
Saudi Arabia	King Faisal Specialist Hospital & Research Centre; Oncology	Riyadh
Slovakia	Narodny onkologicky ustav	Bratislava
Spain	Hospital Universitari Germans Trias i Pujol; Servicio de Oncologia	Badalona	Barcelona
Spain	Hospital Clínic i Provincial; Servicio de Oncología	Barcelona
Spain	Hospital de la Santa Creu i Sant Pau; Servicio de Oncologia	Barcelona
Spain	Hospital del Mar Barcelona	Barcelona
Spain	Hospital Duran i Reynals; Oncologia	Barcelona
Spain	Hospital de Basurto; Servicio de Oncologia	Bilbao	Vizcaya
Spain	Hospital San Pedro De Alcantara; Servicio de Oncologia	Caceres
Spain	Hospital Universitario Reina Sofia; Servicio de Oncologia	Córdoba	Cordoba
Spain	Hospital Universitari de Girona Dr. Josep Trueta; Servicio de Oncologia	Girona
Spain	Hospital General Universitario de Guadalajara; Servicio de Oncologia	Guadalajara
Spain	Hospital Universitario de Canarias;servicio de Oncologia	La Laguna	Tenerife
Spain	Hospital Lucus Augusti; Servicio de Oncologia	Lugo
Spain	Hospital Clinico San Carlos; Servicio de Oncologia	Madrid
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 12 de Octubre; Servicio de Oncologia	Madrid
Spain	Hospital Universitario La Paz; Servicio de Oncologia	Madrid
Spain	Hospital Clinico Universitario Virgen de la Victoria; Servicio de Oncologia	Malaga
Spain	Complejo Hospitalario de Althaia; Servicio de Oncologia	Manresa	Barcelona
Spain	Hospital General Universitario J.M Morales Meseguer; Servicio de Oncologia	Murcia
Spain	Hospital de Navarra; Servicio de Oncologia	Navarra
Spain	Complejo Hospitalario de Orense; Servicio de Oncologia	Orense
Spain	Hospital Univ. Central de Asturias; Servicio de Oncologia	Oviedo	Asturias
Spain	Hospital Universitario Son Espases; Servicio de Oncologia	Palma De Mallorca	Islas Baleares
Spain	Corporacio Sanitaria Parc Tauli; Servicio de Oncologia	Sabadell	Barcelona
Spain	Hospital Univ Vall d'Hebron; Servicio de Oncologia	Sant Andreu de La Barca	Barcelona
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	Complejo Hospitalario de Toledo- H. Virgen de la Salud; Servicio de Oncologia	Toledo
Spain	Hospital Clínico Universitario de Valencia; Servicio de Oncología	Valencia
Spain	Hospital General Universitario de Valencia; Servicio de oncologia	Valencia
Spain	Hospital La Fe	Valencia
Switzerland	Universitaetsspital Basel; Onkologie	Basel
Switzerland	Ospedale Regionale di Bellinzona Medizin Onkologie	Bellinzona
Switzerland	Inselspital Bern; Universitätsklinik für Medizinische Onkologie, Klinische Forschungseinheit	Bern
Switzerland	Kantonsspital Graubünden Medizin Onkologie; Onkologie und Hämatologie	Chur
Switzerland	Hôpitaux Universit. de Genève Médecine Oncologie; Oncologie	Geneve
Switzerland	Luzerner Kantonsspital; Medizinische Onkologie	Luzern
Switzerland	Kantonsspital Winterthur; Medizinische Onkologie	Winterthur
Taiwan	National Cheng Kung Uni Hospital; Dept of Hematology and Oncology	Tainan
Taiwan	Chang Gung Medical Foundation-Linkou, Urinary Oncology	Taoyuan
United Kingdom	Velindre Cancer Centre	Cardiff
United Kingdom	Raigmore Hospital; Dept of Radiotherapy & Oncology	Inverness
United Kingdom	Leicester Royal Infirmary NHS Trust	Leicester
United Kingdom	Barts and the London NHS Trust.	London
United Kingdom	Royal Marsden NHS Foundation Trust	Sutton

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

Argentina,  Australia,  Austria,  Belgium,  Brazil,  Bulgaria,  Canada,  China,  Colombia,  Croatia,  Czechia,  Denmark,  Estonia,  Germany,  Greece,  Hungary,  India,  Ireland,  Italy,  Lebanon,  Lithuania,  Netherlands,  Poland,  Portugal,  Romania,  Russian Federation,  Saudi Arabia,  Slovakia,  Spain,  Switzerland,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Adverse Events (AEs)	AEs were defined as any untoward medical occurrence in a subject administered a pharmaceutical product, regardless of causal attribution. An AE can be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. New disease, exacerbation of existing disease, recurrence of an intermittent medical condition not present at baseline, any deterioration in a laboratory value or other clinical test associated with symptoms or leading to a change in study/concomitant treatment or discontinuation from study drug as well as events related to protocol-mandated interventions are considered AEs.	Baseline up to end of study (up to approximately 6 years)
Secondary	Overall Survival (OS)	OS was defined as date of death (due to any cause) or censoring minus date of start of study treatment plus 1.	Randomization until death from any cause (up to approximately 6 years)
Secondary	Progression Free Survival (PFS) as Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)	PFS was defined as the date of first occurrence of tumor progression (earliest of the dates of the RECIST component indicating tumor progression) or date of death (in the absence of tumor progression) by any cause, whichever occurred first, or date of censoring minus date of start of study treatment plus 1.	Randomization up to disease progression or death from any cause, whichever occurred first (up to approximately 6 years)
Secondary	PFS as Per Modified Response Evaluation Criteria in Solid Tumors (Modified RECIST)	PFS as per Modified RECIST was defined as: date of first occurrence of tumor progression after a modified confirmed response if the participant was a responder according to modified RECIST or; date of first occurrence of tumor progression in case the participant was not a responder according to modified RECIST or; date of death (in the absence of tumor progression) by any cause, or; date of censoring whichever occurred first, minus date of start of study treatment plus 1	Randomization up to disease progression or death from any cause, whichever occurred first (up to approximately 6 years)
Secondary	Percentage of Participants With Best Overall Response (BOR) as Assessed by RECIST v1.1	BOR was assessed by the investigators according to the RECIST v1.1. BOR was defined as a complete response (CR) or partial response (PR) determined on two consecutive investigator assessments >= 4 weeks apart in participants with measurable disease at baseline. CR = Disappearance of all target lesions. Any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to <10 millimeters (mm); PR = At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. Progressive Disease (PD) = At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (nadir), including baseline. In addition to the relative increase of 20%, the sum must have demonstrated an absolute increase of at least 5 mm. Stable Disease (SD) = Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum on study.	Randomization up to disease progression or death from any cause, whichever occurred first (up to approximately 6 years)
Secondary	Percentage of Participants With BOR as Assessed by Modified RECIST	BOR was assessed by the investigators according to the modified RECIST. BOR was defined as complete response (CR) or partial response (PR). CR includes complete disappearance of all tumor lesions and no new measurable or unmeasurable lesions confirmed by a consecutive assessment >=4 weeks from the first documented date. PR is a decrease in the sum of the diameters of all target and all new measurable lesions >=30%, relative to baseline, in the absence of CR confirmed by a consecutive assessment >=4 weeks from the first documented date. The assessment of BOR included post-screening RECIST assessments obtained up to: 1) death from any cause, 2) last evaluable RECIST assessment in the absence of death, 3) start of a subsequent anti-cancer therapy, whichever occurred first.	Randomization up to disease progression or death from any cause, whichever occurred first (up to approximately 6 years)
Secondary	Percentage of Participants With Disease Control as Assessed by RECIST v1.1	Disease control was determined separately on disease status using RECIST v1.1 by the investigator. Disease control rate was defined as the sum of the complete response, partial response, and stable disease rates.	Randomization up to disease progression or death from any cause, whichever occurred first (up to approximately 6 years)
Secondary	Percentage of Participants With Disease Control as Assessed by Modified RECIST	Disease control was determined separately on disease status using modified RECIST by the investigator. Disease control rate was defined as the sum of the complete response, partial response, and stable disease rates.	Randomization up to disease progression or death from any cause, whichever occurred first (up to approximately 6 years)
Secondary	Duration of Response (DOR) as Assessed by RECIST v1.1	Duration of response was determined separately on disease status using RECIST v1.1 by the investigator. For overall responders, DoR was defined as the time from the date of first occurrence of a confirmed response (complete response or partial response) to date of tumor progression or death from any cause, or to censoring date: 1) end of response coincided with the date of tumor progression or death (in the absence of tumor progression) used for the PFS endpoint, 2) for a participant without disease progression or death following a response, the censored end of response coincided with the PFS censoring date (that was latest RECIST assessment or start of subsequent cancer therapy, whichever occurred first).	Time from first occurrence of a documented response to disease progression or death from any cause, whichever occurred first (up to approximately 6 years)
Secondary	DOR as Assessed by Modified RECIST	Duration of response was determined separately on disease status using modified RECIST by the investigator. For overall responders, DoR was defined as the time from the date of first occurrence of a confirmed response (complete response or partial response) to date of tumor progression following that confirmed response or death from any cause, or to censoring date: 1) end of response was the date of tumor progression after that confirmed response or death (in the absence of tumor progression), 2) for a participant without disease progression or death following a response, the censored end of response was the latest RECIST assessment or start of subsequent cancer therapy, whichever occurred first.	Time from first occurrence of a documented response to disease progression or death from any cause, whichever occurred first (up to approximately 6 years)
Secondary	Change From Baseline in Health-Related Quality of Life (HRQoL), as Assessed Using European Organization for Research and Treatment of Cancer (EORTC) Quality-of-Life Questionnaire Core 30 (QLQ-C30) Score	The EORTC QLQ-C30 included global health status, functional scales (physical, role, emotional, cognitive, and social), symptom scales (fatigue, nausea/vomiting, and pain) and single items (dyspnoea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Most questions used a 4-point scale (1 'Not at all' to 4 'Very much'; 2 questions used 7-point scale [1 'very poor' to 7 'Excellent']). Scores were averaged and transformed to 0 - 100 scale. Higher scores on the global health status and functional scales indicated better health status/function. Higher scores on the symptoms scales and symptom items indicated greater symptom burden.	Baseline, Day 1 of Cycles 1, 2, 3 and thereafter every 9 weeks for 54 weeks from study treatment start; and then every 12 weeks until progression/study discontinuation (up to approximately 6 years) (Cycle length = 21 days)
Secondary	Change From Baseline in European Quality of Life (EuroQoL) Group 5-Dimension 5-Level (EQ-5D-5L) Self Report Questionnaire Health Utility Score	The EuroQol 5-Dimension Questionnaire (EQ-5D-5L) is a self-report health status questionnaire that consists of 6 questions used to calculate a health utility score for use in health economic analysis. There are two components to the EuroQol EQ-5D: 1) five health dimensions that assess mobility, self-care, usual activities, pain/discomfort, and anxiety/depression; 2) a visual analogue scale (VAS) that measures health state. There are 5 response levels for each dimension (1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems, and 5=extreme problems) with the highest level representing the worst outcome. The VAS is scored on a scale from 0 to 100, with 0 representing the worst imaginable health and 100 representing the best imaginable health.	Baseline, Day 1 of Cycles 1, 2, 3 and thereafter every 9 weeks for 54 weeks from study treatment start; and then every 12 weeks until progression/study discontinuation (up to approximately 6 years) (Cycle length = 21 days)