Study of Cabozantinib in Combination With Atezolizumab Versus Sorafenib in Subjects With Advanced HCC Who Have Not Received Previous Systemic Anticancer Therapy

Phase 3

Active, not recruiting

Brief 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. A single-agent cabozantinib arm will be enrolled in which subjects receive single agent cabozantinib in order to determine its contribution to the overall safety and efficacy of the combination with atezolizumab.

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.

Recruitment & Eligibility

Inclusion Criteria

Histological or cytological diagnosis of HCC or clinical diagnosis of HCC in cirrhotic patients by CT or MRI per the AASLD 2018 or EASL 2018 guidelines.
The subject has disease that is not amenable to a curative treatment approach (eg, transplant, surgery, ablation therapy) or locoregional therapy (eg, TACE).
Measurable disease per 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.

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). Subjects 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

Arm && Interventions

Group	Intervention	Description
Experimental arm	Cabozantinib	Subjects with advanced HCC will receive cabozantinib 40 mg oral, qd + atezolizumab 1200 mg infusion, q3w
Experimental arm	Atezolizumab	Subjects with advanced HCC will receive cabozantinib 40 mg oral, qd + atezolizumab 1200 mg infusion, q3w
Single-Agent Cabozantinib arm	Cabozantinib	Subjects with advanced HCC will receive cabozantinib 60 mg qd
Control arm	Sorafenib	Subjects with advanced HCC will receive sorafenib 400 mg bid (twice a day)

Primary Outcome Measures

Name	Time	Method
Duration of Progression Free Survival (PFS) for the experimental arm vs. the control arm	Up to 27 months after the first subject is randomized. 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.	Duration of PFS per Response Evaluable Criteria in Solid Tumors version 1.1 (RECIST 1.1)
Duration of Overall Survival (OS) for the experimental arm vs. the control arm	Up to 36 months after the first subject is randomized. Defined as time from randomization to date of death from any cause.

Secondary Outcome Measures

Name	Time	Method
Duration of Progression Free Survival (PFS) for the single-agent arm vs. the control arm	Up to 20 months after the first subject is randomized.	Duration of PFS per RECIST 1.1 by BIRC

Locations (245): Exelixis Clinical Site #208
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Phoenix, Arizona, United States
Exelixis Clinical Site #159
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Tucson, Arizona, United States
Exelixis Clinical Site #44
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La Jolla, California, United States
Exelixis Clinical Site #112
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Los Angeles, California, United States
Exelixis Clinical Site #200
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Orange, California, United States
Exelixis Clinical Site #2
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Rialto, California, United States
Exelixis Clinical Site #207
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San Diego, California, United States
Exelixis Clinical Site #109
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San Francisco, California, United States
Exelixis Clinical Site #54
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San Francisco, California, United States
Exelixis Clinical Site #58
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Washington, District of Columbia, United States
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Exelixis Clinical Site #208
🇺🇸Phoenix, Arizona, United States