Study of Cabozantinib in Combination With Atezolizumab Versus Second NHT in Subjects With mCRPC

Prostate Adenocarcinoma Clinical Trial

— CONTACT-02  

Official title:

A Phase 3, Randomized, Open-Label, Controlled Study of Cabozantinib (XL184) in Combination With Atezolizumab vs Second Novel Hormonal Therapy (NHT) in Subjects With Metastatic Castration-Resistant Prostate Cancer

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04446117
• Other study ID #: XL184-315
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: June 30, 2020
• Est. completion date: August 31, 2024

Study information

• Verified date: July 2023
• Source: Exelixis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a Phase 3, multi-center, randomized, open-label, controlled study designed to evaluate the safety and efficacy of cabozantinib given in combination with atezolizumab versus a second novel hormonal therapy (NHT) in men with metastatic castration-resistant prostate cancer (mCRPC) who have previously been treated with one, and only one, NHT for their prostate cancer disease.

Description:

The primary objective of this study is to evaluate the efficacy of cabozantinib (XL184) in combination with atezolizumab versus a second NHT (abiraterone or enzalutamide) in subjects with mCRPC who have previously been treated with one, and only one, NHT (e.g. abiraterone, apalutamide, darolutamide, or enzalutamide) to treat metastatic castration-sensitive prostate cancer (mCSPC), non-metastatic CRPC (M0 CRPC), or mCRPC, and who have measurable extrapelvic disease. The multiple primary efficacy endpoints comparing the experimental arm and control arm are Duration of Progression Free Survival (PFS) per RECIST 1.1 by Blinded Independent Radiology Committee (BIRC) and Duration of Overall Survival (OS). The secondary efficacy endpoint is Objective Response Rate (ORR) per RECIST 1.1 per BIRC.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 575
• Est. completion date: August 31, 2024
• Est. primary completion date: June 30, 2023
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Men with histologically or cytologically confirmed adenocarcinoma of the prostate

• Prior treatment with one, and only one, NHT (eg, abiraterone, apalutamide, darolutamide, or enzalutamide) for castration-sensitive locally advanced (T3 or T4) or mCSPC, M0 CRPC, or mCRPC

• Surgical or medical castration, with serum testosterone = 50 ng/dL (= 1.73 nmol/L) at screening

• Measurable (extrapelvic soft tissue) metastatic disease per Investigator assessment defined by at least one of the following: measurable visceral disease (eg, adrenal, kidney, liver, lung, pancreas, spleen) per RECIST 1.1; OR measurable extrapelvic adenopathy (ie, adenopathy above the aortic bifurcation)

• Progressive disease at study entry as defined by specific criteria for prostate specific antigen (PSA) progression OR soft tissue disease progression in the opinion of the Investigator (Note: subjects with bone disease progression alone are not eligible)

• Age = 18 years old or meeting country definition of adult, whichever is older, on the day of consent

• ECOG performance status of 0 or 1

• Recovery to baseline or = Grade 1 per Common Terminology Criteria for Adverse Events (CTCAE) v5 from toxicities related to any prior treatments, unless AE(s) are clinically nonsignificant and/or stable on supportive therapy in the opinion of the Investigator

• Adequate organ and marrow function based upon specific laboratory assessments obtained within 21 days prior to randomization

• Understanding and ability to comply with protocol requirements

Exclusion Criteria:

• Any prior nonhormonal therapy initiated for the treatment of mCRPC

• Receipt of abiraterone within 1 week; cyproterone within 10 days; or flutamide, nilutamide, bicalutamide, enzalutamide, or other androgen-receptor inhibitors within 2 weeks before randomization

• Radiation therapy within 4 weeks (2 weeks for bone metastases) prior to randomization (subjects with clinically relevant ongoing complications from prior radiation therapy are not eligible)

• Known brain metastases or cranial epidural disease unless adequately treated and clinically stable at least 4 weeks prior to randomization

• Symptomatic or impending spinal cord compression or cauda equina syndrome

• Concomitant anticoagulation with oral anticoagulants (some specific exceptions apply)

• Administration of a live, attenuated vaccine within 30 days prior to randomization

• Systematic treatment with, or any condition requiring, either corticosteroids (>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days prior to randomization

• Uncontrolled, significant intercurrent or recent illness

• Major surgery within 4 weeks prior to randomization

• Corrected QT interval calculated by the Fridericia formula (QTcF) > 480 ms per ECG within 21 days before randomization

• Inability or unwillingness to swallow pills or receive IV administration

• Previously identified allergy or hypersensitivity to components of the study treatment formulations or history of severe infusion-related reactions to monoclonal antibodies

• Any other active malignancy at time of randomization or diagnosis of another malignancy within 2 years prior to randomization that requires active treatment (some exceptions apply such as locally curable cancers that have apparently been cured).

Related Conditions & MeSH terms

• Metastatic Prostate Cancer
• Prostate Adenocarcinoma
• Prostatic Neoplasms

Intervention

Drug:
• Cabozantinib
Supplied as 20-mg tablets; administered orally daily at 40mg
• Atezolizumab
Supplied as 1200 mg/20 mL vials; administered as an IV infusion once every 3 weeks (q3w)
• Abiraterone Acetate
Supplied as 500 mg tablets; administered orally daily at 1000mg with prednisone 5 mg orally bid
• Enzalutamide
Supplied as 40 mg capsules; administered orally daily at 160mg
• Prednisone
Supplied as 5 mg tablets; administered orally bid at 5 mg with abiraterone 1000mg orally daily

Locations

Country	Name	City	State
Argentina	Exelixis Clinical Site #200	Buenos Aires
Argentina	Exelixis Clinical Site #256	Caba
Argentina	Exelixis Clinical Site #122	Ciudad Autonoma de Buenos Aire	Buenos Aires
Argentina	Exelixis Clinical Site #44	Ciudad Autonoma de Buenos Aire
Argentina	Exelixis Clinical Site #210	Córdoba	Cordoba
Argentina	Exelixis Clinical Site #105	La Rioja
Argentina	Exelixis Clinical Site #120	Mar Del Plata	Buenos Aires
Argentina	Exelixis Site #170	Pergamino	Buenos Aires
Argentina	Exelixis Clinical #261	Rosario	Santa Fe
Argentina	Exelixis Clinical Site #183	Rosario	Santa Fe
Argentina	Exelixis Clinical Site #124	San Juan
Argentina	Exelixis Clinical Site #101	San Salvador De Jujuy
Argentina	Exelixis Clinical Site #152	Viedma	Rio Negro
Australia	Exelixis Clinical Site #115	Adelaide
Australia	Exelixis Clinical Site #79	Ballarat	Victoria
Australia	Exelixis Clinical Site #149	Box Hill
Australia	Exelixis Clinical Site #253	Chermside	Queensland
Australia	Exelixis Clinical Site #95	Frankston	Victoria
Australia	Exelixis Clinical Site #151	Garran	Australian Capital Territory
Australia	Exelixis Clinical #262	Geelong	Victoria
Australia	Exelixis Clinical Site #103	Launceston	Tasmania
Australia	Exelixis Clinical Site #53	Melbourne	Victoria
Australia	Exelixis Clinical Site #252	Port Macquarie	New South Wales
Australia	Exelixis Clinical Stie #260	Saint Albans	Victoria
Australia	Exelixis Clinical Site #175	Saint Leonards	New South Wales
Australia	Exelixis Clinical Site # 189	Sydney	New South Wales
Australia	Exelixis Site #162	Wollongong	New South Wales
Austria	Exelixis Clinical Site #156	Linz	Oberösterreich
Austria	Exelixis Site #158	Linz	Oberösterreich
Austria	Exelixis Clinical Site #218	Wien
Belgium	Exelixis Clinical Site #126	Bonheiden	Antwerpen
Belgium	Exelixis Clinical Site #141	Brussels
Belgium	Exelixis Clinical Site #39	Gent	Oost-Vlaanderen
Belgium	Exelixis Site #165	Roeselare
Brazil	Exelixis Clinical Site #154	Barretos
Brazil	Exelixis Clinical Site #132	Blumenau	Santa Catarina
Brazil	Exelixis Clinical Site #191	Campinas	Sao Paulo
Brazil	Exelixis Clinical Site #204	Curitiba	Parana
Brazil	Exelixis Site #163	Curitiba	Paraná
Brazil	Exelixis Clinical Site #140	Fortaleza
Brazil	Exelixis Clinical Site #153	Porto Alegre
Brazil	Exelixis Site #157	Porto Alegre	Rio Grande Do Sul
Brazil	Exelixis Clinical Site #128	Ribeirão Preto	São Paulo
Brazil	Exelixis Clinical Site #145	Ribeirão Preto
Brazil	Exelixis Clinical Site #171	Rio De Janeiro	RJ
Brazil	Exelixis Clinical Site #116	Santa Cruz Do Sul
Brazil	Exelixis Clinical Site #106	São José Do Rio Preto	São Paulo
Brazil	Exelixis Site #161	Sao Paulo	SP
Canada	Exelixis Clinical Site #69	Edmonton	Alberta
Canada	Exelixis Clinical Site #178	Granby	Quebec
Canada	Exelixis Clinical Site #83	Hamilton	Ontario
Canada	Exelixis Clinical Site #112	Kelowna	British Columbia
Canada	Exelixis Clinical Site #127	London	Ontario
Canada	Exelixis Clinical Site #147	Moncton	New Brunswick
Canada	Exelixis Site #160	Montréal	Quebec
Canada	Exelixis Clinical Site #7	Oakville	Ontario
Chile	Exelixis Clinical Site #142	Providencia
Chile	Exelixis Clinical Site #148	Recoleta
Chile	Exelixis Clinical #263	Santiago	Región Metropolitana
Chile	Exelixis Clinical Site #90	Santiago
Chile	Exelixis Clinical Site #139	Santiago de Chile	Región Metropolitana De Santiago
Chile	Exelixis Clinical Site #113	Temuco
Chile	Exelixis Clinical Site #119	Valparaíso
Chile	Exelixis Clinical Site #247	Viña del Mar	Región De Valparaíso
Czechia	Exelixis Clinical Site #129	Brno
Czechia	Exelixis Clinical Site #130	Olomouc
Czechia	Exelixis Clinical Site #31	Praha
Czechia	Exelixis Clinical Site #63	Praha 2	Praha
Czechia	Exelixis Clinical Site #80	Praha 2
Czechia	Exelixis Clinical Site #47	Praha 8
France	Exelixis Clinical Site #134	Brest
France	Exelixis Clinical Site #77	Clermont-Ferrand
France	Exelixis Clinical Site #155	Dijon cedex
France	Exelixis Clinical Site #74	Hyères
France	Exelixis Clinical Site #222	La Roche-sur-Yon Cedex 9
France	Exelixis Clinical Site #146	Nîmes
France	Exelixis Clinical Site #38	Paris
France	Exelixis Clinical Site #66	Quimper
France	Exelixis Clinical Site #214	Reims
France	Exelixis Clinical Site #135	Saint-Grégoire
France	Exelixis Clinical Site #213	Strasbourg
France	Exelixis Clinical Site #36	Strasbourg
France	Exelixis Clinical Site #73	Toulouse
France	Exelixis Clinical Site #85	Toulouse
France	Exelixis Clinical Site #230	Vandoeuvre les nancy
Georgia	Exelixis Clinical Site #10	Tbilisi
Georgia	Exelixis Clinical Site #11	Tbilisi
Georgia	Exelixis Clinical Site #15	Tbilisi
Georgia	Exelixis Clinical Site #16	Tbilisi
Georgia	Exelixis Clinical Site #8	Tbilisi
Georgia	Exelixis Clinical Site #9	Tbilisi
Germany	Exelixis Clinical Site #227	Berlin
Germany	Exelixis Clinical Site #180	Duisburg	North Rhine-Westphalia
Germany	Exelixis Clinical Site #98	Gutersloh	Nordrhein-Westfalen
Germany	Exelixis Clinical Site #239	Hamburg
Germany	Exelixis Clinical Site #273	Hannover
Germany	Exelixis Clinical Site #185	Lübeck	Schleswig-Holstein
Germany	Exelixis Clinical Site #179	Münster	North Rhine-Westphalia
Germany	Exelixis Clinical Site #176	Nürtingen	Baden-Wuerttemberg
Germany	Exelixis Clinical Site #136	Tübingen
Greece	Exelixis Clinical Site #238	Athens	Attica
Greece	Exelixis Clinical Site #93	Cholargós	Attica
Greece	Exelixis Clinical Site #45	Heraklion	Crete
Greece	Exelixis Clinical Site #97	Larissa	Thessaly
Greece	Exelixis Clinical Site #92	Maroúsi	Attica
Greece	Exelixis Clinical Site #202	Maroussi	Attica
Greece	Exelixis Clinical Site #244	Nea Kifisia	Attica
Greece	Exelixis Clinical Site #99	Néo Fáliro	Attica
Greece	Exelixis Clinical Site #64	Thessaloníki	Macedonia
Hungary	Exelixis Clinical Site #109	Budapest
Hungary	Exelixis Clinical Site #118	Budapest
Hungary	Exelixis Clinical Site #207	Budapest
Hungary	Exelixis Clinical Site #57	Budapest
Hungary	Exelixis Clinical Site #240	Debrecen
Hungary	Exelixis site #167	Gyula
Israel	Exelixis Clinical Site #55	Haifa
Israel	Exelixis Clinical Site #27	Jerusalem
Israel	Exelixis Clinical Site #150	Petah tikva
Israel	Exelixis Clinical Site #117	Ramat Gan
Israel	Exelixis Clinical Site #30	Safed
Israel	Exelixis Clinical Site #35	Tel Aviv
Italy	Exelixis Clinical Site #217	Ancona
Italy	Exelixis Clinical Site #121	Firenze
Italy	Exelixis Site #168	Meldola	FC
Italy	Exelixis Clinical Site #192	Milan
Italy	Exelixis Clinical Site #258	Milano
Italy	Exelixis Clinical #267	Parma
Italy	Exelixis Clinical Site #237	Pavia
Italy	Exelixis Clinical Site #107	Perugia
Italy	Exelixis Clinical #269	Pisa
Italy	Exelixis Clinical Site #234	Roma
Italy	Exelixis Clinical Site #62	Roma
Italy	Exelixis Clinical Site #246	Rozzano	Milano
Italy	Exelixis Site #156	Sondrio	SO
Italy	Exelixis Clinical Site #96	Terni
Italy	Exelixis Clinical Site #199	Trento	Trentino
Japan	Exelixis Clinical Site #100	Akita-Shi	Akita
Japan	Exelixis Clinical Site #78	Chiba
Japan	Exelixis Clinical Site #88	Chuo-Ku	Osaka-shi
Japan	Exelixis Clinical Site #209	Fukuoka
Japan	Exelixis Clinical Site #51	Hidaka	Saitama
Japan	Exelixis Clinical Site #104	Hirosaki	Aomori
Japan	Exelixis Clinical Site #43	Kashiwa-shi	Chiba
Japan	Exelixis Clinical Site #84	Kita-gun	Kagawa
Japan	Exelixis Clinical Site #52	Kobe	Hyogo
Japan	Exelixis Clinical Site #70	Kobe	Hyogo
Japan	Exelixis Clinical Site #26	Nagano
Japan	Exelixis Clinical Site #211	Natori-shi	Miyagi
Japan	Exelixis Clinical Site #81	Osaka-sayama
Japan	Exelixis Clinical Site #68	Sagamihara	Kanagawa
Japan	Exelixis Clinical Site #54	Sakura-shi	Chiba
Japan	Exelixis Clinical Site #37	Sapporo	Hokkaido
Japan	Exelixis Clinical Site #72	Sapporo	Hokkaido
Japan	Exelixis Clinical Site #65	Shinjuku-Ku	Tokyo
Japan	Exelixis Clinical Site #216	Shizuoka City	Shizuoka
Japan	Exelixis Clinical Site #75	Tokyo
Japan	Exelixis Clinical Site #232	Toyota-shi	Aichi
Japan	Exelixis Clinical Site #61	Ube	Yamaguchi
Japan	Exelixis Clinical Site #32	Wakayama
Japan	Exelixis Clinical Site #22	Yokohama-shi	Kanagawa
Korea, Republic of	Exelixis Clinical Site #24	Busan
Korea, Republic of	Exelixis Clinical Site #58	Busan
Korea, Republic of	Exelixis Clinical Site #21	Daegu
Korea, Republic of	Exelixis Clinical Site #94	Daegu
Korea, Republic of	Exelixis Clinical Site #49	Goyang-si	Gyeonggi-do
Korea, Republic of	Exelixis Clinical Site #40	Gwangju
Korea, Republic of	Exelixis Clinical Site #34	Hwasun	Jeollanam-do
Korea, Republic of	Exelixis Clinical Site #20	Junggu	Daejeon
Korea, Republic of	Exelixis Clinical Site #60	Seongnam-si	Gyeonggi-Do
Korea, Republic of	Exelixis Clinical Site #25	Seoul
Korea, Republic of	Exelixis Clinical Site #46	Seoul
Korea, Republic of	Exelixis Clinical Site #48	Seoul
Korea, Republic of	Exelixis Clinical Site #59	Seoul
Mexico	Exelixis Clinical Site #208	Culiacán	Sinaloa
Mexico	Exelixis Clinical Site #173	Guadalajara	Jalisco
Mexico	Exelixis Clinical Site #212	Guadalajara	Jalisco
Mexico	Exelixis Clinical Site #254	Leon	Guanajuato
Mexico	Exelixis Clinical Site #174	Mexico City
Mexico	Exelixis Clinical Site #187	Mexico City	Distrito Federal
Mexico	Exelixis Clinical Site #257	Monterrey	Nuevo Leon
Mexico	Exelixis Clinical Site #272	Puebla
Mexico	Exelixis Clinical Site #172	Querétaro	Queretaro
Mexico	Exelixis Clinical Site #182	Querétaro	Queretaro
Mexico	Exelixis Clinical Site #184	San Luis Potosí	San Luis Potosi
Mexico	Exelixis Clinical Site #250	San Luis Potosí	San Luis Potosi
Mexico	Exelixis Clinical Site #206	Tuxtla Gutiérrez	Chiapas
Mexico	Exelixis Clinical Site #219	Zapopan	Jalisco
Poland	Exelixis Clinical Site #82	Bydgoszcz
Poland	Exelixis Clinical #268	Lódz
Poland	Exelixis Clinical Site #243	Otwock	Mazowieckie
Poland	Exelixis Clinical Site #89	Poznan
Portugal	Exelixis Clinical Site #110	Braga
Portugal	Exelixis Clinical Site #188	Guimarães
Portugal	Exelixis Clinical Site #197	Lisboa
Portugal	Exelixis Site #164	Lisboa
Portugal	Exelixis Clinical Site #196	Loures
Portugal	Exelixis Clinical Site #223	Porto
Portugal	Exelixis Clinical Site #56	Porto
Portugal	Exelixis Clinical Site #193	Vila Real
Russian Federation	Exelixis Site #166	Moscow
Russian Federation	Exelixis Clinical Site #137	Saint Petersburg
Russian Federation	Exelixis Clinical Site #195	Saint Petersburg
Singapore	Exelixis Clinical Site #181	Singapore
Singapore	Exelixis Clinical Site #50	Singapore
Singapore	Exelixis Clinical Site #87	Singapore
Spain	Exelixis Clinical Site #17	Alcorcón	Madrid
Spain	Exelixis Clinical Site #274	Badalona
Spain	Exelixis Clinical Site #190	Barcelona
Spain	Exelixis Clinical Site #228	Barcelona
Spain	Exelixis Clinical Site #23	Barcelona
Spain	Exelixis Clinical Site #255	Barcelona
Spain	Exelixis Clinical Site #226	Cadiz
Spain	Exelixis Clinical Site #33	Córdoba
Spain	Exelixis Clinical Site #229	Elche	Alicante
Spain	Exelixis Clinical Site #28	Lugo
Spain	Exelixis Clinical Site #13	Madrid
Spain	Exelixis Clinical Site #131	Madrid
Spain	Exelixis Clinical Site #236	Madrid
Spain	Exelixis Clinical Site #248	Madrid
Spain	Exelixis Clinical Site #251	Madrid
Spain	Exelixis Clinical #270	Málaga
Spain	Exelixis Clinical Site #12	Manresa	Barcelona
Spain	Exelixis Clinical Site #225	Oviedo	Asturias
Spain	Exelixis Clinical Site #220	Palma De Mallorca	Islas Baleares
Spain	Exelixis Clinical Site #233	Santiago de Compostela	La Coruna
Spain	Exelixis Clinical Site #29	Sevilla
Taiwan	Exelixis Clinical #266	Kaohsiung
Taiwan	Exelixis Clinical Site #138	Kaohsiung
Taiwan	Exelixis Clinical Site #133	Taichung
Taiwan	Exelixis Clinical Site #86	Taichung City
Taiwan	Exelixis Clinical Site #111	Tainan
Taiwan	Exelixis Clinical Site #271	Tainan City
Taiwan	Exelixis Clinical #264	Taipei city
Taiwan	Exelixis Clinical #265	Taoyuan
Ukraine	Exelixis Clinical Site #102	Dnipro
Ukraine	Exelixis Clinical Site #186	Dnipro
Ukraine	Exelixis Clinical Site #76	Kyiv
Ukraine	Exelixis Clinical Site #71	Luts'k
United Kingdom	Exelixis Clinical Site #249	Blackburn	Lancashire
United Kingdom	Exelixis Clinical Site #205	London	England
United Kingdom	Exelixis Clinical Site #231	Northwood	Middlesex
United Kingdom	Exelixis Clinical Site #235	Surrey Quays	England
United Kingdom	Exelixis Clinical Site #194	Swansea	Wales
United Kingdom	Exelixis Clinical Site #241	Taunton	England
United States	Winship Cancer Institute of Emory University	Atlanta	Georgia
United States	Exelixis Clinical Site #91	Aurora	Colorado
United States	Exelixis Clinical Site #6	Baltimore	Maryland
United States	Exelixis Clinical Site #198	Bronx	New York
United States	Exelixis Site #159	Cleveland	Ohio
United States	Exelixis Clinical Site #14	Denver	Colorado
United States	Non-participating Site	Detroit	Michigan
United States	Exelixis Clinical Site #42	Duarte	California
United States	Exelixis Clinical Site #123	East Brunswick	New Jersey
United States	Exelixis Clinical Site #2	Fullerton	California
United States	Exelixis Clinical Site #177	Houston	Texas
United States	Exelixis Clinical Site #259	Houston	Texas
United States	Exelixis Clinical Site #5	Houston	Texas
United States	Exelixis Clinical Site #224	La Jolla	California
United States	Exelixis Clinical Site #144	Las Vegas	Nevada
United States	Non-participating Site	Lawrenceville	New Jersey
United States	Exelixis Clinical Site #242	Louisville	Kentucky
United States	Exelixis Clinical Site #108	Miami	Florida
United States	Exelixis Clinical Site #1	Nashville	Tennessee
United States	Yale University School of Medicine	New Haven	Connecticut
United States	Yale University, School of Medicine	New Haven	Connecticut
United States	Weill Cornell Medical College	New York	New York
United States	Exelixis Clinical Site #221	Oklahoma City	Oklahoma
United States	Exelixis Clinical Site #19	Omaha	Nebraska
United States	Exelixis Clinical Site #18	Philadelphia	Pennsylvania
United States	Exelixis Clinical Site #201	Pittsburgh	Pennsylvania
United States	Exelixis Clinical Site #143	Roanoke	Virginia
United States	Exelixis Clinical Site #203	Rochester	Minnesota
United States	Exelixis Clinical Site #67	Salt Lake City	Utah
United States	Exelixis Clinical Site #114	San Diego	California
United States	Exelixis Clinical Site #125	Santa Monica	California
United States	Exelixis Clinical Site #245	Stanford	California
United States	Exelixis Clinical Site #41	Temple	Texas
United States	Exelixis Clinical Site #4	Tucson	Arizona
United States	Exelixis Clinical Site #215	Westwood	Kansas

Sponsors (3)

Lead Sponsor	Collaborator
Exelixis	Roche-Genentech, Takeda

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belgium,  Brazil,  Canada,  Chile,  Czechia,  France,  Georgia,  Germany,  Greece,  Hungary,  Israel,  Italy,  Japan,  Korea, Republic of,  Mexico,  Poland,  Portugal,  Russian Federation,  Singapore,  Spain,  Taiwan,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Duration of Progression Free Survival per Response Evaluable Criteria in Solid Tumors version 1.1 (RECIST 1.1)	Defined as time from randomization to the earlier of progressive disease (PD) per RECIST 1.1 as determined by the Blinded Independent Radiology Committee (BIRC) or death from any cause	Approximately 21 months after the first subject is randomized.
Primary	Duration of Overall Survival (OS)	Defined as time from randomization to date of death from any cause	Approximately 37 months after the first subject is randomized
Secondary	Objective response rate (ORR)	ORR per RECIST 1.1 by BIRC	Approximately 37 months after the first subject is randomized