AzTrials
AzTrials

Hepatocellular CarcinomaPhase 3COSMIC-312NCT03755791

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

A Phase 3 study testing Cabozantinib, Sorafenib and Atezolizumab in people with Hepatocellular Carcinoma, run by Exelixis at 245 sites in 34 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Hepatocellular Carcinoma
What is being tested?
Cabozantinib, Sorafenib and Atezolizumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
837 participants
Where
245 sitesin 34 countries
Study dates
10 Jun 2018to 31 Jul 2026
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.

Trial locations and contacts

245 sites in 34 countries.

245 sites in 34 countries

United States33 sites

  • Exelixis Clinical Site #76

    Albuquerque, New Mexico, 87131

  • Exelixis Clinical Site #4

    Atlanta, Georgia, 30318

  • Exelixis Clinical Site #6

    Baltimore, Maryland, 21202

  • Exelixis Clinical Site #7

    Burlington, Massachusetts, 01805

  • Exelixis Clinical Site #12

    Chapel Hill, North Carolina, 27599-7600

  • Exelixis Clinical Site #144

    Charleston, South Carolina, 29425

  • Exelixis Clinical Site #195

    Chicago, Illinois, 60612

  • Exelixis Clinical Site #120

    Chicago, Illinois, 60637

  • Exelixis Clinical Site #199

    Dallas, Texas, 75246

  • Exelixis Clinical Site #154

    Houston, Texas, 77030

  • Exelixis Clinical Site #11

    Kansas City, Missouri, 64128

  • Exelixis Clinical Site #5

    Kansas City, Missouri, 64131

  • Exelixis Clinical Site #44

    La Jolla, California, 92037

  • Exelixis Clinical Site #1

    Las Vegas, Nevada, 89169

  • Exelixis Clinical Site #112

    Los Angeles, California, 90033

  • Exelixis Clinical Site #191

    Miami, Florida, 33125

  • Exelixis Clinical Site #14

    New Brunswick, New Jersey, 08903

  • Exelixis Clinical Site #200

    Orange, California, 92868-3201

  • Exelixis Clinical Site #88

    Philadelphia, Pennsylvania, 19107

  • Exelixis Clinical Site #208

    Phoenix, Arizona, 85004

  • Exelixis Clinical Site #176

    Portland, Oregon, 97213

  • Exelixis Clinical Site #2

    Rialto, California, 92377

  • Exelixis Clinical Site #207

    San Diego, California, 92093

  • Exelixis Clinical Site #109

    San Francisco, California, 94115

  • Exelixis Clinical Site #54

    San Francisco, California, 94158

  • Exelixis Clinical Site #13

    Seattle, Washington, 98101

  • Exelixis Clinical Site #46

    Seattle, Washington, 98109

  • Exelixis Clinical Site #3

    Spokane, Washington, 99208

  • Exelixis Clinical Site #8

    St Louis, Missouri, 63110

  • Exelixis Clinical Site #19

    Temple, Texas, 76508

  • Exelixis Clinical Site #39

    Toledo, Ohio, 43614

  • Exelixis Clinical Site #159

    Tucson, Arizona, 85719

  • Exelixis Clinical Site #58

    Washington D.C., District of Columbia, 20007

Other trials in United States

China24 sites

  • Exelixis Site #239

    Beijing, 100034

  • Exelixis Clinical Site #237

    Beijing, 100050

  • Exelixis Clinical Site #246

    Changchun, Jilin, 130012

  • Exelixis Clinical Site #229

    Changchun, Jilin, 130021

  • Exelixis Clinical Site #231

    Changsha, Hunan, 410008

  • Exelixis Clinical Site #224

    Changsha, Hunan, 410013

  • Exelixis Site #241

    Changsha, Hunan, 410013

  • Exelixis Clinical Site #235

    Chengdu, Sichuan, 610041

  • Exelixis Clinical Site #228

    Fuzhou, Fujian, 350014

  • Exelixis Clinical Site #242

    Guangzhou, Guangdong, 510280

  • Exelixis Clinical Site #218

    Hangzhou, Zhejiang, 310016

  • Exelixis Clinical Site #223

    Hangzhou, Zhejiang, 310022

  • Exelixis Clinical Site #227

    Harbin, Heilongjiang, 150081

  • Exelixis Clinical Site #233

    Hefei, Anhui, 230036

  • Exelixis Clinical Site #234

    Jiangyin, Jiansu, 214400

  • Exelixis Clinical Site #226

    Linyi, Shandong, 276000

  • Exelixis Clinical Site #221

    Nanchang, Jiangxi, 330006

  • Exelixis Clinical Site #238

    Nanchang, Jiangxi, 330006

  • Exelixis Clinical Site #185

    Nanjing, Jiangsu, 210002

  • Exelixis Site #240

    Shanghai, 200001

  • Exelixis Clinical Site #232

    Shanghai, 201305

  • Exelixis Clinical Site #236

    Shenyang, Liaoning, 110006

  • Exelixis Clinical Site #225

    Xiamen, Fujian, 361004

  • Exelixis Clinical Site #230

    Zhengzhou, Henan, 450008

Other trials in China

France14 sites

  • Exelixis Clinical Site #43

    Amiens, 80054

  • Exelixis Clinical Site #27

    Besançon, 25030

  • Exelixis Clinical Site #56

    Bondy, 93140

  • Exelixis Clinical Site #29

    Caen, 14033

  • Exelixis Clinical Site #48

    Clichy, 92110

  • Exelixis Clinical Site #23

    Grenoble, 38043

  • Exelixis Clinical Site #55

    Lille, 59037

  • Exelixis Clinical Site #16

    Lyon, 69317

  • Exelixis Clinical Site #31

    Montbéliard, 25250

  • Exelixis Clinical Site #49

    Montpellier, 34295

  • Exelixis Clinical Site #47

    Nantes, 44093

  • Exelixis Clinical Site #51

    Nice, 06202

  • Exelixis Clinical Site #20

    Pessac, 33604

  • Exelixis Clinical Site #32

    Vandœuvre-lès-Nancy, 54511

Other trials in France

Brazil12 sites

  • Exelixis Clinical Site #175

    Barretos, São Paulo, 14784-400

  • Exelixis Clinical Site #89

    Belo Horizonte, Minas Gerais, 30110-022

  • Exelixis Clinical Site #98

    Belo Horizonte, Minas Gerais, 30130-090

  • Exelixis Clinical Site #113

    Curitiba, Paraná, 81520-060

  • Exelixis Clinical Site #121

    Jaú, São Paulo, 17210-120

  • Exelixis Clinical Site #203

    Porto Alegre, Rio Grande do Sul, 90050-170

  • Exelixis Clinical Site #184

    Salvador, Estado de Bahia, 40110-060

  • Exelixis Clinical Site #186

    São Paulo, São Paulo, 01246-900

  • Exelixis Clinical Site #156

    São Paulo, São Paulo, 01321-001

  • Exelixis Clinical Site #187

    São Paulo, São Paulo, 01509-010

  • Exelixis Clinical Site #181

    São Paulo, São Paulo, 04538-132

  • Exelixis Clinical Site #91

    São Paulo, 04543-000

Other trials in Brazil

Australia11 sites

  • Exelixis Clinical Site #107

    Box Hill, Victoria, 3128

  • Exelixis Clinical Site #78

    Camperdown, New South Wales, 2050

  • Exelixis Clinical Site #165

    Darlinghurst, New South Wales, 2010

  • Exelixis Clinical Site #142

    Greenslopes, Queensland, 4120

  • Exelixis Clinical Site #166

    Heidelberg, Victoria, 3084

  • Exelixis Clinical Site #171

    Kingswood, New South Wales, 2747

  • Exelixis Clinical Site #126

    Kogarah, New South Wales, 2217

  • Exelixis Clinical Site #17

    Kurralta Park, South Australia

  • Exelixis Clinical Site #190

    Nedlands, Western Australia, 6009

  • Exelixis Clinical Site #72

    Parkville, Victoria, 3050

  • Exelixis Clinical Site #155

    Westmead, New South Wales, 2145

Other trials in Australia

Italy11 sites

  • Exelixis Clinical Site #158

    Bologna, 40138

  • Exelixis Clinical Site #152

    Brescia, 25124

  • Exelixis Clinical Site #147

    Milan, 20122

  • Exelixis Clinical Site #149

    Naples, 80131

  • Exelixis Clinical Site #131

    Novara, 28100

  • Exelixis Clinical Site #167

    Roma, 00168

  • Exelixis Clinical Site #53

    Rozzano, Milano, 20089

  • Exelixis Clinical Site #177

    Torino, 10126

  • Exelixis Clinical Site #182

    Torino, 10128

  • Exelixis Clinical Site #163

    Tricase, Lecce, 73039

  • Exelixis Clinical Site #243

    Udine, 33100

Other trials in Italy

South Korea11 sites

  • Exelixis Clinical Site #77

    Busan, 47392

  • Exelixis Clinical Site #86

    Busan, 49201

  • Exelixis Clinical Site #114

    Busan, 49241

  • Exelixis Clinical Site #157

    Goyang-si, Gyeonggi-do, 10408

  • Exelixis Clinical Site #75

    Incheon, 22332

  • Exelixis Clinical Site #104

    Seoul, 03080

  • Exelixis Clinical Site #105

    Seoul, 03080

  • Exelixis Clinical Site #99

    Seoul, 05505

  • Exelixis Clinical Site #79

    Seoul, 06273

  • Exelixis Clinical Site #93

    Seoul, 06351

  • Exelixis Clinical Site #127

    Suwon, Gyeonggi-do, 16499

Other trials in South Korea

Russia9 sites

  • Exelixis Clinical Site #81

    Kaluga, 248007

  • Exelixis Clinical Site #74

    Kislino, Kursk Oblast, 305524

  • Exelixis Clinical Site #95

    Krasnodar, 350040

  • Exelixis Clinical Site #108

    Moscow, 115478

  • Exelixis Clinical Site #101

    Murmansk, 183047

  • Exelixis Clinical Site #80

    Nizhny Novgorod, 603137

  • Exelixis Clinical Site #111

    Saint Petersburg, 197758

  • Exelixis Clinical Site #90

    Saint Petersburg, 197758

  • Exelixis Clinical Site #73

    Sochi, 354057

Other trials in Russia

Spain9 sites

  • Exelixis Clinical Site #103

    Barcelona, 08908

  • Exelixis Clinical Site #164

    Madrid, 28007

  • Exelixis Clinical Site #63

    Madrid, 28046

  • Exelixis Clinical Site #21

    Majadahonda, Madrid, 28222

  • Exelixis Clinical Site #22

    Majadahonda, Madrid, 28222

  • Exelixis Clinical Site #59

    Pamplona, Navarre, 31008

  • Exelixis Clinical Site #28

    Santander, Cantabria, 39008

  • Exelixis Clinical Site #168

    Valencia, 46009

  • Exelixis Clinical Site #45

    Zaragoza, 50009

Other trials in Spain

Taiwan9 sites

  • Exelixis Clinical Site #119

    Changhua, 500

  • Exelixis Clinical Site #162

    Kaohsiung City, 833

  • Exelixis Clinical Site #161

    Taichung, 407

  • Exelixis Clinical Site #197

    Tainan, 704

  • Exelixis Clinical Site #145

    Tainan, 736

  • Exelixis Clinical Site #82

    Taipei, 10002

  • Exelixis Clinical Site #128

    Taipei, 10491

  • Exelixisi Clinical Site #100

    Taipei, 11217

  • Exelixis Clinical Site #94

    Taoyuan, 333

Other trials in Taiwan

Belgium7 sites

  • Exelixis Clinical Site #50

    Brussels, California, 1070

  • Exelixis Clinical Site #65

    Brussels, 1200

  • Exelixis Clinical Site #169

    Edegem, 2650

  • Exelixis Clinical Site #148

    Ghent, 9000

  • Exelixis Clinical Site #57

    Haine-Saint-Paul, 7100

  • Exelixis Clinical Site #188

    Leuven, 3000

  • Exelixis Clinical Site #102

    Liège, 4000

Other trials in Belgium

Canada7 sites

  • Exelixis Clinical Site #71

    Calgary, Alberta, T2N 4N2

  • Exelixis Clinical Site #205

    Edmonton, Alberta, T6G 2B7

  • Exelixis Clinical Site #222

    Halifax, Nova Scotia, B3H 2Y9

  • Exelixis Clinical Site #194

    Hamilton, Ontario, L8V 5C2

  • Exelixis Clinical Site #85

    Montreal, Quebec, H3T 1E2

  • Exelixis Clinical Site #212

    Ottawa, Ontario, K1H 8L6

  • Exelixis Clinical Site #34

    Winnipeg, Manitoba, R3E 0V9

Other trials in Canada

Mexico7 sites

  • Exelixis Clinical Site #135

    León, Guanajuato, 37000

  • Exelixis Clinical Site #133

    Mexico City, 06700

  • Exelixis Clinical Site #160

    Mexico City, 06760

  • Exelixis Clinical Site #132

    Monterrey, Nuevo León, 64000

  • Exelixis Clinical Site #134

    San Luis Potosí City, 78250

  • Exelixis Clinical Site #141

    Tuxtla Gutiérrez, Chiapas, 29038

  • Exelixis Clinical Site #153

    Veracruz, 94300

Other trials in Mexico

Argentina6 sites

  • Exelixis Clinical Site #217

    City of Buenos Aires, Buenos Aires, C1118AAT

  • Exelixis Clinical Site #213

    City of Buenos Aires, Buenos Aires, C1199ABB

  • Exelixis Clinical Site #216

    City of Buenos Aires, Buenos Aires, C1264AAA

  • Exelixis Clinical Site #219

    Pilar, Buenos Aires, B1629ODT

  • Exelixis Clinical Site #220

    Rosario, Santa Fe Province, 2000

  • Exelixis Clinical Site #201

    Rosario, Santa Fe Province, S2000CVB

Other trials in Argentina

Turkey (Türkiye)6 sites

  • Exelixis Clinical Site #193

    Ankara, 06010

  • Exelixis Clinical Site #178

    Ankara, 06230

  • Exelixis Clinical Site #173

    Edirne, 22030

  • Exelixis Clinical Site #189

    Istanbul, Instanbul, 34098

  • Exelixis Clinical Site #179

    Istanbul, 34214

  • Exelixis Clinical Site #180

    Malatya, 44280

Other trials in Turkey (Türkiye)

United Kingdom6 sites

  • Exelixis Clinical Site #196

    Belfast, Northern Ireland, BT9 7AB

  • Exelixis Clinical Site #83

    Bristol, England, BS2 8ED

  • Exelixis Clinical Site #87

    Cambridge, England, CB2 0QQ

  • Exelixis Clinical Site #151

    London, England, NW3 2QG

  • Exelixis Clinical Site #129

    London, England, W12 0HS

  • Exelixis Clinical Site #192

    Manchester, England, M20 4BX

Other trials in United Kingdom

Austria5 sites

  • Exelixis Clinical Site #198

    Graz, Styria, 8036

  • Exelixis Clinical Site #150

    Klagenfurt, Carinthia, 9020

  • Exelixis Clinical Site #64

    Linz, Upper Austria, 4010

  • Exelixis Clinical Site #137

    Sankt Pölten, Lower Austria, 3100

  • Exelixis Clinical Site #174

    Vienna, 1090

Other trials in Austria

Georgia5 sites

  • Exelixis Clinical Site #69

    Batumi, 6000

  • Exelixis Clinical Site #66

    Tbilisi, 0112

  • Exelixis Clinical Site #68

    Tbilisi, 0114

  • Exelixis Clinical Site #67

    Tbilisi, 0144

  • Exelixis Clinical Site #70

    Tbilisi, 0186

Other trials in Georgia

Romania5 sites

  • Exelixis Clinical Site #206

    Bucharest, 022328

  • Exelixis Clinical Site #204

    Cluj-Napoca, Cluj, 400015

  • Exelixis Clinical Site #211

    Cluj-Napoca, Cluj, 400015

  • Exelixis Clinical Site #202

    Cluj-Napoca, Cluj, 400641

  • Exelixis Clinical Site #209

    Iași, 700483

Other trials in Romania

Ukraine5 sites

  • Exelixis Clinical Site #125

    Chernivtsi, 58013

  • Exelixis Clinical Site #122

    Dnipro, 49102

  • Exelixis Clinical Site #123

    Kharkiv, 61070

  • Exelixis Clinical Site #124

    Odesa, 65055

  • Exelixis Clinical Site #138

    Uzhhorod, 88000

Other trials in Ukraine

Czechia4 sites

  • Exelixis Clinical Site #18

    Hradec Králové, 500 05

  • Exelixis Clinical Site #37

    Olomouc, 779 00

  • Exelixis Clinical Site #10

    Prague, 140 59

  • Exelixis Clinical Site #38

    Prague, 150 06

Other trials in Czechia

Germany4 sites

  • Exelixis Clinical Site #214

    Berlin, 13125

  • Exelixis Clinical Site #244

    Frankfurt am Main, Hesse, 60590

  • Exelixis Clinical Site #215

    Hamburg, 20246

  • Exelixis Clinical Site #210

    Kassel, Hesse, 34125

Other trials in Germany

Israel4 sites

  • Exelixis Clinical Site #30

    Jerusalem, 9112001

  • Exelixis Clinical Site #33

    Petah Tikva, 4941492

  • Exelixis Clinical Site #40

    Ramat Gan, 5262101

  • Exelixis Clinical Site #35

    Rehovot, 7661041

Other trials in Israel

Netherlands4 sites

  • Exelixis Clinical Site #52

    Amsterdam, North Holland, 1105 AZ

  • Exelixis Clinical Site #92

    Maastricht, Limburg, 6229 HX

  • Exelixis Clinical Site #84

    Rotterdam, South Holland, 3015 GD

  • Exelixis Clinical Site #36

    Utrecht, 3584 CX

Other trials in Netherlands

Switzerland4 sites

  • Exelixis Clinical Site #115

    Basel, 4031

  • Exelixis Clinical Site #172

    Bern, 3010

  • Exelixis Clinical Site #110

    Sankt Gallen, 9007

  • Exelixis Clinical Site #61

    Zurich, 8091

Other trials in Switzerland

Thailand4 sites

  • Exelixis Clinical Site #143

    Chiang Mai, 50200

  • Exelixis Clinical Site #139

    Hat Yai, Changwat Songkhla, 90110

  • Exelixis Clinical Site #183

    Khon Kaen, 40002

  • Exelixis Clinical Site #96

    Pathum Wan, Bangkok, 10330

Other trials in Thailand

Hong Kong3 sites

  • Exelixis Clinical Site #146

    Hong Kong

  • Exelixis Clinical Site #42

    Hong Kong

  • Exelixis Clinical Site #9

    Hong Kong

Other trials in Hong Kong

Hungary3 sites

  • Exelixis Clinical Site #140

    Budapest, 1083

  • Exelixis Clinical Site #25

    Debrecen, 4032

  • Exelixis Clinical Site #26

    Szeged, 6720

Other trials in Hungary

Philippines3 sites

  • Exelixis Clinical Site #118

    Cebu City, 6000

  • Exelixis Clinical Site #117

    Pasig, 1605

  • Exelixis Clinical Site #136

    Quezon City, 1102

Other trials in Philippines

Poland3 sites

  • Exelixis Clinical Site #24

    Gdansk, Pomeranian Voivodeship, 80-952

  • Exelixis Clinical Site #15

    Mysłowice, Silesian Voivodeship, 41-400

  • Exelixis Clinical Site #41

    Warsaw, Masovian Voivodeship, 02-507

Other trials in Poland

Singapore3 sites

  • Exelixis Clinical Site #106

    Singapore, 169610

  • Exelixis Clinical Site #97

    Singapore, 217562

  • Exelixis Clinical Site #116

    Singapore, 308433

Other trials in Singapore

New Zealand2 sites

  • Exelixis Clinical Site #60

    Grafton, Auckland, 1023

  • Exelixis Clinical Site #62

    Newton, Wellington Region, 6021

Other trials in New Zealand

Colombia1 site

  • Exelixis Clinical Site #130

    Montería, Departamento de Córdoba, 230002

Other trials in Colombia

Ireland1 site

  • Exelixis Clinical Site #170

    Dublin, 8

Other trials in Ireland

About this study

Official title: 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.

Read the 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.

Keywords
liver, cancer, hepatocellular, carcinoma
Medical subject headings
Carcinoma, Hepatocellular, Neoplasms, Carcinoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CabozantinibDrug

    Also called XL184, Cabometyx®

    Supplied as 20-mg tablets; administered orally daily at 40 mg

  • CabozantinibDrug

    Also called XL184, Cabometyx®

    Supplied as 60-mg tablets; administered orally once daily at 60 mg

  • SorafenibDrug

    Also called Nexavar®

    Supplied as 200-mg tablets; administered orally twice daily at 400 mg

  • AtezolizumabDrug

    Also called Tecentriq®

    Supplied as 1200 mg/20 mL (60 mg/mL) in sing-dose vials; administered as an intravenous (IV) infusion q3w

Study groups in NCT03755791
Study groupRoleWhat they receive
Experimental armExperimentalParticipants with advanced HCC will receive cabozantinib 40 milligrams (mg) oral, once daily (qd) + atezolizumab 1200 mg infusion, once every 3 weeks (q3w)
Receives: Drug: Cabozantinib; Drug: Atezolizumab
Control armActive comparatorParticipants with advanced HCC will receive sorafenib 400 mg twice a day (bid)
Receives: Drug: Sorafenib
Single-Agent Cabozantinib armOtherParticipants with advanced HCC will receive cabozantinib 60 mg qd
Receives: Drug: Cabozantinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression Free Survival (PFS) for the Experimental Arm Versus the Control Arm in the PFS Intent to Treat (PITT) Population

    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.

    Measured: From the date of first participant randomization up to 28 months

  2. Overall Survival (OS) for the Experimental Arm Versus the Control Arm in the ITT Population

    OS was defined as the time from randomization to death due to any cause.

    Measured: From the date of first participant randomization up to 36 months

Secondary outcomes (1)

  1. PFS for the Single-Agent Cabozantinib Arm Versus the Control Arm in the ITT Population

    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.

    Measured: From the date of first participant randomization up to 28 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Nov 2018
  2. Study start10 Jun 2018
  3. Primary completion30 Nov 2021
  4. Study completion31 Jul 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
At least 740 eligible participants with advanced HCC will be randomized in a 2:1:1 ratio. Experimental arm (at least 370 participants) will receive cabozantinib plus atezolizumab. Control arm (at least 185 participants) will receive sorafenib. Single-agent cabozantinib arm (at least185 participants) will receive single-agent cabozantinib
Masking
None (open label)
Enrolment
837 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03755791
Sponsor's protocol ID
XL184-312
Other IDs
2024-516479-34-00
Acronym
COSMIC-312
Status last verified
Nov 2025
First submitted
26 Nov 2018
Last updated
11 Dec 2025
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Yau T, Kaseb A, Cheng AL, Qin S, Zhu AX, Chan SL, Melkadze T, Sukeepaisarnjaroen W, Breder V, Verset G, Gane E, Borbath I, Rangel JDG, Ryoo BY, Makharadze T, Merle P, Benzaghou F, Milwee S, Wang Z, Curran D, Kelley RK, Rimassa L. Cabozantinib plus atezolizumab versus sorafenib for advanced hepatocellular carcinoma (COSMIC-312): final results of a randomised phase 3 study. Lancet Gastroenterol Hepatol. 2024 Apr;9(4):310-322. doi: 10.1016/S2468-1253(23)00454-5. Epub 2024 Feb 13.

    PubMed 38364832

  • Kelley RK, Rimassa L, Cheng AL, Kaseb A, Qin S, Zhu AX, Chan SL, Melkadze T, Sukeepaisarnjaroen W, Breder V, Verset G, Gane E, Borbath I, Rangel JDG, Ryoo BY, Makharadze T, Merle P, Benzaghou F, Banerjee K, Hazra S, Fawcett J, Yau T. Cabozantinib plus atezolizumab versus sorafenib for advanced hepatocellular carcinoma (COSMIC-312): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2022 Aug;23(8):995-1008. doi: 10.1016/S1470-2045(22)00326-6. Epub 2022 Jul 4.

    PubMed 35798016

  • Kelley RK, W Oliver J, Hazra S, Benzaghou F, Yau T, Cheng AL, Rimassa L. Cabozantinib in combination with atezolizumab versus sorafenib in treatment-naive advanced hepatocellular carcinoma: COSMIC-312 Phase III study design. Future Oncol. 2020 Jul;16(21):1525-1536. doi: 10.2217/fon-2020-0283. Epub 2020 Jun 3.

    PubMed 32491932

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Cabozantinib, Sorafenib and Atezolizumab in people with Hepatocellular Carcinoma, run by Exelixis at 245 sites in 34 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 11 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 245 sites in United States, China, France, Brazil, Australia and 29 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 11 Dec 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03755791, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Dec 2025.

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