Study of Cabozantinib in Combination With Atezolizumab Versus Sorafenib in Participants With Advanced Hepatocellular Carcinoma (HCC) Who Have Not Received Previous Systemic Anticancer Therapy (COSMIC-312)

November 25, 2025 updated by: Exelixis

A Randomized, Controlled Phase 3 Study of Cabozantinib (XL184) in Combination With Atezolizumab Versus Sorafenib in Subjects With Advanced Hepatocellular Carcinoma Who Have Not Received Previous Systemic Anticancer Therapy

This Phase 3 study evaluates the safety and efficacy of cabozantinib in combination with atezolizumab versus the standard of care sorafenib in adults with advanced hepatocellular carcinoma (HCC) who have not received previous systemic anticancer therapy. A single-agent cabozantinib arm will be enrolled in which participants receive single agent cabozantinib in order to determine its contribution to the overall safety and efficacy of the combination with atezolizumab.

Study Overview

Status

Active, not recruiting

Conditions

Hepatocellular Carcinoma

Intervention / Treatment

Detailed Description

This is a multicenter, randomized, open-label, controlled Phase 3 trial of cabozantinib in combination with atezolizumab versus sorafenib in adults with advanced HCC who have not received previous systemic anticancer therapy in the advanced HCC setting. The primary objective of this study is to evaluate the effect of cabozantinib in combination with atezolizumab on the duration of progression-free survival (PFS) and duration of overall survival (OS) versus sorafenib. The secondary objective is to evaluate the activity of single-agent cabozantinib compared with sorafenib in this patient population.

Study Type

Interventional

Enrollment (Actual)

837

Phase

Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Argentina
- Buenos Aires
  - City of Buenos Aires, Buenos Aires, Argentina, C1118AAT
    - Exelixis Clinical Site #217
  - City of Buenos Aires, Buenos Aires, Argentina, C1199ABB
    - Exelixis Clinical Site #213
  - City of Buenos Aires, Buenos Aires, Argentina, C1264AAA
    - Exelixis Clinical Site #216
  - Pilar, Buenos Aires, Argentina, B1629ODT
    - Exelixis Clinical Site #219
- Santa Fe Province
  - Rosario, Santa Fe Province, Argentina, 2000
    - Exelixis Clinical Site #220
  - Rosario, Santa Fe Province, Argentina, S2000CVB
    - Exelixis Clinical Site #201
Australia
- New South Wales
  - Camperdown, New South Wales, Australia, 2050
    - Exelixis Clinical Site #78
  - Darlinghurst, New South Wales, Australia, 2010
    - Exelixis Clinical Site #165
  - Kingswood, New South Wales, Australia, 2747
    - Exelixis Clinical Site #171
  - Kogarah, New South Wales, Australia, 2217
    - Exelixis Clinical Site #126
  - Westmead, New South Wales, Australia, 2145
    - Exelixis Clinical Site #155
- Queensland
  - Greenslopes, Queensland, Australia, 4120
    - Exelixis Clinical Site #142
- South Australia
  - Kurralta Park, South Australia, Australia
    - Exelixis Clinical Site #17
- Victoria
  - Box Hill, Victoria, Australia, 3128
    - Exelixis Clinical Site #107
  - Heidelberg, Victoria, Australia, 3084
    - Exelixis Clinical Site #166
  - Parkville, Victoria, Australia, 3050
    - Exelixis Clinical Site #72
- Western Australia
  - Nedlands, Western Australia, Australia, 6009
    - Exelixis Clinical Site #190
Austria
- - Vienna, Austria, 1090
    - Exelixis Clinical Site #174
- Carinthia
  - Klagenfurt, Carinthia, Austria, 9020
    - Exelixis Clinical Site #150
- Lower Austria
  - Sankt Pölten, Lower Austria, Austria, 3100
    - Exelixis Clinical Site #137
- Styria
  - Graz, Styria, Austria, 8036
    - Exelixis Clinical Site #198
- Upper Austria
  - Linz, Upper Austria, Austria, 4010
    - Exelixis Clinical Site #64
Belgium
- - Brussels, Belgium, 1200
    - Exelixis Clinical Site #65
  - Edegem, Belgium, 2650
    - Exelixis Clinical Site #169
  - Ghent, Belgium, 9000
    - Exelixis Clinical Site #148
  - Haine-Saint-Paul, Belgium, 7100
    - Exelixis Clinical Site #57
  - Leuven, Belgium, 3000
    - Exelixis Clinical Site #188
  - Liège, Belgium, 4000
    - Exelixis Clinical Site #102
- California
  - Brussels, California, Belgium, 1070
    - Exelixis Clinical Site #50
Brazil
- - São Paulo, Brazil, 04543-000
    - Exelixis Clinical Site #91
- Estado de Bahia
  - Salvador, Estado de Bahia, Brazil, 40110-060
    - Exelixis Clinical Site #184
- Minas Gerais
  - Belo Horizonte, Minas Gerais, Brazil, 30110-022
    - Exelixis Clinical Site #89
  - Belo Horizonte, Minas Gerais, Brazil, 30130-090
    - Exelixis Clinical Site #98
- Paraná
  - Curitiba, Paraná, Brazil, 81520-060
    - Exelixis Clinical Site #113
- Rio Grande do Sul
  - Porto Alegre, Rio Grande do Sul, Brazil, 90050-170
    - Exelixis Clinical Site #203
- São Paulo
  - Barretos, São Paulo, Brazil, 14784-400
    - Exelixis Clinical Site #175
  - Jaú, São Paulo, Brazil, 17210-120
    - Exelixis Clinical Site #121
  - São Paulo, São Paulo, Brazil, 01246-900
    - Exelixis Clinical Site #186
  - São Paulo, São Paulo, Brazil, 01321-001
    - Exelixis Clinical Site #156
  - São Paulo, São Paulo, Brazil, 01509-010
    - Exelixis Clinical Site #187
  - São Paulo, São Paulo, Brazil, 04538-132
    - Exelixis Clinical Site #181
Canada
- Alberta
  - Calgary, Alberta, Canada, T2N 4N2
    - Exelixis Clinical Site #71
  - Edmonton, Alberta, Canada, T6G 2B7
    - Exelixis Clinical Site #205
- Manitoba
  - Winnipeg, Manitoba, Canada, R3E 0V9
    - Exelixis Clinical Site #34
- Nova Scotia
  - Halifax, Nova Scotia, Canada, B3H 2Y9
    - Exelixis Clinical Site #222
- Ontario
  - Hamilton, Ontario, Canada, L8V 5C2
    - Exelixis Clinical Site #194
  - Ottawa, Ontario, Canada, K1H 8L6
    - Exelixis Clinical Site #212
- Quebec
  - Montreal, Quebec, Canada, H3T 1E2
    - Exelixis Clinical Site #85
China
- - Beijing, China, 100034
    - Exelixis Site #239
  - Beijing, China, 100050
    - Exelixis Clinical Site #237
  - Shanghai, China, 200001
    - Exelixis Site #240
  - Shanghai, China, 201305
    - Exelixis Clinical Site #232
- Anhui
  - Hefei, Anhui, China, 230036
    - Exelixis Clinical Site #233
- Fujian
  - Fuzhou, Fujian, China, 350014
    - Exelixis Clinical Site #228
  - Xiamen, Fujian, China, 361004
    - Exelixis Clinical Site #225
- Guangdong
  - Guangzhou, Guangdong, China, 510280
    - Exelixis Clinical Site #242
- Heilongjiang
  - Harbin, Heilongjiang, China, 150081
    - Exelixis Clinical Site #227
- Henan
  - Zhengzhou, Henan, China, 450008
    - Exelixis Clinical Site #230
- Hunan
  - Changsha, Hunan, China, 410008
    - Exelixis Clinical Site #231
  - Changsha, Hunan, China, 410013
    - Exelixis Clinical Site #224
  - Changsha, Hunan, China, 410013
    - Exelixis Site #241
- Jiangsu
  - Nanjing, Jiangsu, China, 210002
    - Exelixis Clinical Site #185
- Jiangxi
  - Nanchang, Jiangxi, China, 330006
    - Exelixis Clinical Site #221
  - Nanchang, Jiangxi, China, 330006
    - Exelixis Clinical Site #238
- Jiansu
  - Jiangyin, Jiansu, China, 214400
    - Exelixis Clinical Site #234
- Jilin
  - Changchun, Jilin, China, 130012
    - Exelixis Clinical Site #246
  - Changchun, Jilin, China, 130021
    - Exelixis Clinical Site #229
- Liaoning
  - Shenyang, Liaoning, China, 110006
    - Exelixis Clinical Site #236
- Shandong
  - Linyi, Shandong, China, 276000
    - Exelixis Clinical Site #226
- Sichuan
  - Chengdu, Sichuan, China, 610041
    - Exelixis Clinical Site #235
- Zhejiang
  - Hangzhou, Zhejiang, China, 310016
    - Exelixis Clinical Site #218
  - Hangzhou, Zhejiang, China, 310022
    - Exelixis Clinical Site #223
Colombia
- Departamento de Córdoba
  - Montería, Departamento de Córdoba, Colombia, 230002
    - Exelixis Clinical Site #130
Czechia
- - Hradec Králové, Czechia, 500 05
    - Exelixis Clinical Site #18
  - Olomouc, Czechia, 779 00
    - Exelixis Clinical Site #37
  - Prague, Czechia, 140 59
    - Exelixis Clinical Site #10
  - Prague, Czechia, 150 06
    - Exelixis Clinical Site #38
France
- - Amiens, France, 80054
    - Exelixis Clinical Site #43
  - Besançon, France, 25030
    - Exelixis Clinical Site #27
  - Bondy, France, 93140
    - Exelixis Clinical Site #56
  - Caen, France, 14033
    - Exelixis Clinical Site #29
  - Clichy, France, 92110
    - Exelixis Clinical Site #48
  - Grenoble, France, 38043
    - Exelixis Clinical Site #23
  - Lille, France, 59037
    - Exelixis Clinical Site #55
  - Lyon, France, 69317
    - Exelixis Clinical Site #16
  - Montbéliard, France, 25250
    - Exelixis Clinical Site #31
  - Montpellier, France, 34295
    - Exelixis Clinical Site #49
  - Nantes, France, 44093
    - Exelixis Clinical Site #47
  - Nice, France, 06202
    - Exelixis Clinical Site #51
  - Pessac, France, 33604
    - Exelixis Clinical Site #20
  - Vandœuvre-lès-Nancy, France, 54511
    - Exelixis Clinical Site #32
Georgia
- - Batumi, Georgia, 6000
    - Exelixis Clinical Site #69
  - Tbilisi, Georgia, 0112
    - Exelixis Clinical Site #66
  - Tbilisi, Georgia, 0114
    - Exelixis Clinical Site #68
  - Tbilisi, Georgia, 0144
    - Exelixis Clinical Site #67
  - Tbilisi, Georgia, 0186
    - Exelixis Clinical Site #70
Germany
- - Berlin, Germany, 13125
    - Exelixis Clinical Site #214
  - Hamburg, Germany, 20246
    - Exelixis Clinical Site #215
- Hesse
  - Frankfurt am Main, Hesse, Germany, 60590
    - Exelixis Clinical Site #244
  - Kassel, Hesse, Germany, 34125
    - Exelixis Clinical Site #210
Hong Kong
- - Hong Kong, Hong Kong
    - Exelixis Clinical Site #146
  - Hong Kong, Hong Kong
    - Exelixis Clinical Site #42
  - Hong Kong, Hong Kong
    - Exelixis Clinical Site #9
Hungary
- - Budapest, Hungary, 1083
    - Exelixis Clinical Site #140
  - Debrecen, Hungary, 4032
    - Exelixis Clinical Site #25
  - Szeged, Hungary, 6720
    - Exelixis Clinical Site #26
Ireland
- - Dublin, Ireland, 8
    - Exelixis Clinical Site #170
Israel
- - Jerusalem, Israel, 9112001
    - Exelixis Clinical Site #30
  - Petah Tikva, Israel, 4941492
    - Exelixis Clinical Site #33
  - Ramat Gan, Israel, 5262101
    - Exelixis Clinical Site #40
  - Rehovot, Israel, 7661041
    - Exelixis Clinical Site #35
Italy
- - Bologna, Italy, 40138
    - Exelixis Clinical Site #158
  - Brescia, Italy, 25124
    - Exelixis Clinical Site #152
  - Milan, Italy, 20122
    - Exelixis Clinical Site #147
  - Napoli, Italy, 80131
    - Exelixis Clinical Site #149
  - Novara, Italy, 28100
    - Exelixis Clinical Site #131
  - Roma, Italy, 00168
    - Exelixis Clinical Site #167
  - Torino, Italy, 10126
    - Exelixis Clinical Site #177
  - Torino, Italy, 10128
    - Exelixis Clinical Site #182
  - Udine, Italy, 33100
    - Exelixis Clinical Site #243
- Lecce
  - Tricase, Lecce, Italy, 73039
    - Exelixis Clinical Site #163
- Milano
  - Rozzano, Milano, Italy, 20089
    - Exelixis Clinical Site #53
Mexico
- - Mexico City, Mexico, 06760
    - Exelixis Clinical Site #160
  - Mexico City, Mexico, 06700
    - Exelixis Clinical Site #133
  - San Luis Potosí City, Mexico, 78250
    - Exelixis Clinical Site #134
  - Veracruz, Mexico, 94300
    - Exelixis Clinical Site #153
- Chiapas
  - Tuxtla Gutiérrez, Chiapas, Mexico, 29038
    - Exelixis Clinical Site #141
- Guanajuato
  - León, Guanajuato, Mexico, 37000
    - Exelixis Clinical Site #135
- Nuevo León
  - Monterrey, Nuevo León, Mexico, 64000
    - Exelixis Clinical Site #132
Netherlands
- - Utrecht, Netherlands, 3584 CX
    - Exelixis Clinical Site #36
- Limburg
  - Maastricht, Limburg, Netherlands, 6229 HX
    - Exelixis Clinical Site #92
- North Holland
  - Amsterdam, North Holland, Netherlands, 1105 AZ
    - Exelixis Clinical Site #52
- South Holland
  - Rotterdam, South Holland, Netherlands, 3015 GD
    - Exelixis Clinical Site #84
New Zealand
- Auckland
  - Grafton, Auckland, New Zealand, 1023
    - Exelixis Clinical Site #60
- Wellington Region
  - Newton, Wellington Region, New Zealand, 6021
    - Exelixis Clinical Site #62
Philippines
- - Cebu City, Philippines, 6000
    - Exelixis Clinical Site #118
  - Pasig, Philippines, 1605
    - Exelixis Clinical Site #117
  - Quezon City, Philippines, 1102
    - Exelixis Clinical Site #136
Poland
- Masovian Voivodeship
  - Warsaw, Masovian Voivodeship, Poland, 02-507
    - Exelixis Clinical Site #41
- Pomeranian Voivodeship
  - Gdansk, Pomeranian Voivodeship, Poland, 80-952
    - Exelixis Clinical Site #24
- Silesian Voivodeship
  - Mysłowice, Silesian Voivodeship, Poland, 41-400
    - Exelixis Clinical Site #15
Romania
- - Bucharest, Romania, 022328
    - Exelixis Clinical Site #206
  - Iași, Romania, 700483
    - Exelixis Clinical Site #209
- Cluj
  - Cluj-Napoca, Cluj, Romania, 400015
    - Exelixis Clinical Site #204
  - Cluj-Napoca, Cluj, Romania, 400015
    - Exelixis Clinical Site #211
  - Cluj-Napoca, Cluj, Romania, 400641
    - Exelixis Clinical Site #202
Russia
- - Kaluga, Russia, 248007
    - Exelixis Clinical Site #81
  - Krasnodar, Russia, 350040
    - Exelixis Clinical Site #95
  - Moscow, Russia, 115478
    - Exelixis Clinical Site #108
  - Murmansk, Russia, 183047
    - Exelixis Clinical Site #101
  - Nizhny Novgorod, Russia, 603137
    - Exelixis Clinical Site #80
  - Saint Petersburg, Russia, 197758
    - Exelixis Clinical Site #111
  - Saint Petersburg, Russia, 197758
    - Exelixis Clinical Site #90
  - Sochi, Russia, 354057
    - Exelixis Clinical Site #73
- Kursk Oblast
  - Kislino, Kursk Oblast, Russia, 305524
    - Exelixis Clinical Site #74
Singapore
- - Singapore, Singapore, 169610
    - Exelixis Clinical Site #106
  - Singapore, Singapore, 217562
    - Exelixis Clinical Site #97
  - Singapore, Singapore, 308433
    - Exelixis Clinical Site #116
South Korea
- - Busan, South Korea, 47392
    - Exelixis Clinical Site #77
  - Busan, South Korea, 49201
    - Exelixis Clinical Site #86
  - Busan, South Korea, 49241
    - Exelixis Clinical Site #114
  - Incheon, South Korea, 22332
    - Exelixis Clinical Site #75
  - Seoul, South Korea, 03080
    - Exelixis Clinical Site #104
  - Seoul, South Korea, 03080
    - Exelixis Clinical Site #105
  - Seoul, South Korea, 05505
    - Exelixis Clinical Site #99
  - Seoul, South Korea, 06273
    - Exelixis Clinical Site #79
  - Seoul, South Korea, 06351
    - Exelixis Clinical Site #93
- Gyeonggi-do
  - Goyang-si, Gyeonggi-do, South Korea, 10408
    - Exelixis Clinical Site #157
  - Suwon, Gyeonggi-do, South Korea, 16499
    - Exelixis Clinical Site #127
Spain
- - Barcelona, Spain, 08908
    - Exelixis Clinical Site #103
  - Madrid, Spain, 28007
    - Exelixis Clinical Site #164
  - Madrid, Spain, 28046
    - Exelixis Clinical Site #63
  - Valencia, Spain, 46009
    - Exelixis Clinical Site #168
  - Zaragoza, Spain, 50009
    - Exelixis Clinical Site #45
- Cantabria
  - Santander, Cantabria, Spain, 39008
    - Exelixis Clinical Site #28
- Madrid
  - Majadahonda, Madrid, Spain, 28222
    - Exelixis Clinical Site #21
  - Majadahonda, Madrid, Spain, 28222
    - Exelixis Clinical Site #22
- Navarre
  - Pamplona, Navarre, Spain, 31008
    - Exelixis Clinical Site #59
Switzerland
- - Basel, Switzerland, 4031
    - Exelixis Clinical Site #115
  - Bern, Switzerland, 3010
    - Exelixis Clinical Site #172
  - Sankt Gallen, Switzerland, 9007
    - Exelixis Clinical Site #110
  - Zurich, Switzerland, 8091
    - Exelixis Clinical Site #61
Taiwan
- - Changhua, Taiwan, 500
    - Exelixis Clinical Site #119
  - Kaohsiung City, Taiwan, 833
    - Exelixis Clinical Site #162
  - Taichung, Taiwan, 407
    - Exelixis Clinical Site #161
  - Tainan, Taiwan, 736
    - Exelixis Clinical Site #145
  - Tainan, Taiwan, 704
    - Exelixis Clinical Site #197
  - Taipei, Taiwan, 10002
    - Exelixis Clinical Site #82
  - Taipei, Taiwan, 10491
    - Exelixis Clinical Site #128
  - Taipei, Taiwan, 11217
    - Exelixisi Clinical Site #100
  - Taoyuan District, Taiwan, 333
    - Exelixis Clinical Site #94
Thailand
- - Chiang Mai, Thailand, 50200
    - Exelixis Clinical Site #143
  - Khon Kaen, Thailand, 40002
    - Exelixis Clinical Site #183
- Bangkok
  - Pathum Wan, Bangkok, Thailand, 10330
    - Exelixis Clinical Site #96
- Changwat Songkhla
  - Hat Yai, Changwat Songkhla, Thailand, 90110
    - Exelixis Clinical Site #139
Turkey (Türkiye)
- - Ankara, Turkey (Türkiye), 06010
    - Exelixis Clinical Site #193
  - Ankara, Turkey (Türkiye), 06230
    - Exelixis Clinical Site #178
  - Edirne, Turkey (Türkiye), 22030
    - Exelixis Clinical Site #173
  - Istanbul, Turkey (Türkiye), 34214
    - Exelixis Clinical Site #179
  - Malatya, Turkey (Türkiye), 44280
    - Exelixis Clinical Site #180
- Instanbul
  - Istanbul, Instanbul, Turkey (Türkiye), 34098
    - Exelixis Clinical Site #189
Ukraine
- - Chernivtsi, Ukraine, 58013
    - Exelixis Clinical Site #125
  - Dnipro, Ukraine, 49102
    - Exelixis Clinical Site #122
  - Kharkiv, Ukraine, 61070
    - Exelixis Clinical Site #123
  - Odesa, Ukraine, 65055
    - Exelixis Clinical Site #124
  - Uzhhorod, Ukraine, 88000
    - Exelixis Clinical Site #138
United Kingdom
- England
  - Bristol, England, United Kingdom, BS2 8ED
    - Exelixis Clinical Site #83
  - Cambridge, England, United Kingdom, CB2 0QQ
    - Exelixis Clinical Site #87
  - London, England, United Kingdom, NW3 2QG
    - Exelixis Clinical Site #151
  - London, England, United Kingdom, W12 0HS
    - Exelixis Clinical Site #129
  - Manchester, England, United Kingdom, M20 4BX
    - Exelixis Clinical Site #192
- Northern Ireland
  - Belfast, Northern Ireland, United Kingdom, BT9 7AB
    - Exelixis Clinical Site #196
United States
- Arizona
  - Phoenix, Arizona, United States, 85004
    - Exelixis Clinical Site #208
  - Tucson, Arizona, United States, 85719
    - Exelixis Clinical Site #159
- California
  - La Jolla, California, United States, 92037
    - Exelixis Clinical Site #44
  - Los Angeles, California, United States, 90033
    - Exelixis Clinical Site #112
  - Orange, California, United States, 92868-3201
    - Exelixis Clinical Site #200
  - Rialto, California, United States, 92377
    - Exelixis Clinical Site #2
  - San Diego, California, United States, 92093
    - Exelixis Clinical Site #207
  - San Francisco, California, United States, 94115
    - Exelixis Clinical Site #109
  - San Francisco, California, United States, 94158
    - Exelixis Clinical Site #54
- District of Columbia
  - Washington D.C., District of Columbia, United States, 20007
    - Exelixis Clinical Site #58
- Florida
  - Miami, Florida, United States, 33125
    - Exelixis Clinical Site #191
- Georgia
  - Atlanta, Georgia, United States, 30318
    - Exelixis Clinical Site #4
- Illinois
  - Chicago, Illinois, United States, 60612
    - Exelixis Clinical Site #195
  - Chicago, Illinois, United States, 60637
    - Exelixis Clinical Site #120
- Maryland
  - Baltimore, Maryland, United States, 21202
    - Exelixis Clinical Site #6
- Massachusetts
  - Burlington, Massachusetts, United States, 01805
    - Exelixis Clinical Site #7
- Missouri
  - Kansas City, Missouri, United States, 64128
    - Exelixis Clinical Site #11
  - Kansas City, Missouri, United States, 64131
    - Exelixis Clinical Site #5
  - St Louis, Missouri, United States, 63110
    - Exelixis Clinical Site #8
- Nevada
  - Las Vegas, Nevada, United States, 89169
    - Exelixis Clinical Site #1
- New Jersey
  - New Brunswick, New Jersey, United States, 08903
    - Exelixis Clinical Site #14
- New Mexico
  - Albuquerque, New Mexico, United States, 87131
    - Exelixis Clinical Site #76
- North Carolina
  - Chapel Hill, North Carolina, United States, 27599-7600
    - Exelixis Clinical Site #12
- Ohio
  - Toledo, Ohio, United States, 43614
    - Exelixis Clinical Site #39
- Oregon
  - Portland, Oregon, United States, 97213
    - Exelixis Clinical Site #176
- Pennsylvania
  - Philadelphia, Pennsylvania, United States, 19107
    - Exelixis Clinical Site #88
- South Carolina
  - Charleston, South Carolina, United States, 29425
    - Exelixis Clinical Site #144
- Texas
  - Dallas, Texas, United States, 75246
    - Exelixis Clinical Site #199
  - Houston, Texas, United States, 77030
    - Exelixis Clinical Site #154
  - Temple, Texas, United States, 76508
    - Exelixis Clinical Site #19
- Washington
  - Seattle, Washington, United States, 98101
    - Exelixis Clinical Site #13
  - Seattle, Washington, United States, 98109
    - Exelixis Clinical Site #46
  - Spokane, Washington, United States, 99208
    - Exelixis Clinical Site #3

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Description

Key Inclusion Criteria:

Histological or cytological diagnosis of HCC or clinical diagnosis of HCC in cirrhotic patients by Computed Tomography (CT) or Computed Tomography (MRI) per the American Association for the Study of Liver Diseases (AASLD) 2018 or European Association for the Study of the Liver (EASL) 2018 guidelines.
The participant has disease that is not amenable to a curative treatment approach (eg, transplant, surgery, ablation therapy) or locoregional therapy (eg, TACE).
Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as determined by the Investigator.
Barcelona Clinic Liver Cancer (BCLC) stage Category B or C.
Child-Pugh Score of A.
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

Key Exclusion Criteria:

Known fibrolamellar carcinoma, sarcomatoid HCC or mixed hepatocellular cholangiocarcinoma.
Prior systemic anticancer therapy for advanced HCC including but not limited to chemotherapy, small molecule kinase inhibitors, and immune checkpoint inhibitors (ICIs). Participants who have received local intratumoral or arterial chemotherapy are eligible; local anticancer therapy within ≥ 28 days before randomization
Radiation therapy for bone metastasis within 2 weeks, any other radiation therapy within 8 weeks prior to randomization.
Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 8 weeks prior to randomization.
Concomitant anticoagulation with oral anticoagulants

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Interventional Model: Parallel Assignment
Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm Participant Group / Arm A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.	Intervention / Treatment Intervention / Treatment A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Experimental arm Participants with advanced HCC will receive cabozantinib 40 milligrams (mg) oral, once daily (qd) + atezolizumab 1200 mg infusion, once every 3 weeks (q3w)	Drug: Cabozantinib Supplied as 20-mg tablets; administered orally daily at 40 mg Other Names: XL184 Cabometyx® Drug: Cabozantinib Supplied as 60-mg tablets; administered orally once daily at 60 mg Other Names: XL184 Cabometyx® Drug: Atezolizumab Supplied as 1200 mg/20 mL (60 mg/mL) in sing-dose vials; administered as an intravenous (IV) infusion q3w Other Names: Tecentriq®
Active Comparator: Control arm Participants with advanced HCC will receive sorafenib 400 mg twice a day (bid)	Drug: Sorafenib Supplied as 200-mg tablets; administered orally twice daily at 400 mg Other Names: Nexavar®
Other: Single-Agent Cabozantinib arm Participants with advanced HCC will receive cabozantinib 60 mg qd	Drug: Cabozantinib Supplied as 20-mg tablets; administered orally daily at 40 mg Other Names: XL184 Cabometyx® Drug: Cabozantinib Supplied as 60-mg tablets; administered orally once daily at 60 mg Other Names: XL184 Cabometyx®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS) for the Experimental Arm Versus the Control Arm in the PFS Intent to Treat (PITT) Population Time Frame: From the date of first participant randomization up to 28 months	PFS was defined as the time from randomization to the earlier of either the date of radiographic progression defined as a 20% increase in the sum of the longest diameters of target lesions, or the unequivocal appearance of new lesions, or progression of non-target disease per Blinded Independent Radiology Committee (BIRC) or the date of death due to any cause per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.	From the date of first participant randomization up to 28 months
Overall Survival (OS) for the Experimental Arm Versus the Control Arm in the ITT Population Time Frame: From the date of first participant randomization up to 36 months	OS was defined as the time from randomization to death due to any cause.	From the date of first participant randomization up to 36 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PFS for the Single-Agent Cabozantinib Arm Versus the Control Arm in the ITT Population Time Frame: From the date of first participant randomization up to 28 months	PFS was defined as the time from randomization to the earlier of either the date of radiographic progression per BIRC or the date of death due to any cause per RECIST version 1.1.	From the date of first participant randomization up to 28 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Exelixis

Investigators

Study Director: Medical Director, Exelixis

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 10, 2018

Primary Completion (Actual)

November 30, 2021

Study Completion (Estimated)

July 31, 2026

Study Registration Dates

First Submitted

November 26, 2018

First Submitted That Met QC Criteria

November 26, 2018

First Posted (Actual)

November 28, 2018

Study Record Updates

Last Update Posted (Actual)

December 11, 2025

Last Update Submitted That Met QC Criteria

November 25, 2025

Last Verified

November 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

XL184-312
2024-516479-34-00 (Ctis)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

product manufactured in and exported from the U.S.

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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Study Overview

Status

Conditions

Intervention / Treatment

Detailed Description

Study Type

Enrollment (Actual)

Phase

Contacts and Locations

Study Locations

Participation Criteria

Eligibility Criteria

Ages Eligible for Study

Accepts Healthy Volunteers

Description

Study Plan

How is the study designed?

Design Details

Number of Arms

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure

Measure Description

Time Frame

Secondary Outcome Measures

Outcome Measure

Measure Description

Time Frame

Collaborators and Investigators

Sponsor

Investigators

Publications and helpful links

General Publications

Study record dates

Study Major Dates

Study Start (Actual)

Primary Completion (Actual)

Study Completion (Estimated)

Study Registration Dates

First Submitted

First Submitted That Met QC Criteria

First Posted (Actual)

Study Record Updates

Last Update Posted (Actual)

Last Update Submitted That Met QC Criteria

Last Verified

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Studies a U.S. FDA-regulated device product

product manufactured in and exported from the U.S.

Clinical Trials on Hepatocellular Carcinoma

Clinical Trials on Cabozantinib

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Drug Interventions

Conditions

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