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NCT Number: NCT03755791

Study of Cabozantinib in Combination With Atezolizumab Versus Sorafenib in Participants With Advanced Hepatocellular Carcinoma (HCC) 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.

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This study is active but is not currently recruiting participants.

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Key information

Conditions

Hepatocellular Carcinoma Adenocarcinoma Carcinoma Carcinoma, Hepatocellular Digestive System Diseases Digestive System Neoplasms Liver Diseases Liver Neoplasms Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Glandular and Epithelial

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Exelixis Clinical Site #213, City of Buenos Aires, Buenos Aires, Argentina

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Cabozantinib

Drug

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

Other names: XL184, Cabometyx®

Sorafenib

Drug

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

Other names: Nexavar®

Atezolizumab

Drug

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

Other names: Tecentriq®

Primary outcomes

  1. 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.

  2. 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.

Secondary outcomes

  1. 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.

Sponsors and collaborators

Lead sponsor

Exelixis

Industry

Registry information

Official study 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

Acronym: COSMIC-312

Important dates

Study start
2018
Primary completion
2021
Study completion
2026
First posted
Nov 28, 2018
Registry last updated
Dec 11, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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