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

Exelixis

Status and phase: Active, not recruiting; Phase 3

Conditions: Hepatocellular Carcinoma

Treatments: Drug: Sorafenib; Drug: Cabozantinib; Drug: Atezolizumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT03755791

XL184-312

Details and patient eligibility

About

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.

Full 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.

Enrollment: 837 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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837 participants in 3 patient groups

Experimental arm

Experimental group

Description:

Subjects with advanced HCC will receive cabozantinib 40 mg oral, qd + atezolizumab 1200 mg infusion, q3w

Treatment:

Drug: Atezolizumab

Drug: Cabozantinib

Drug: Cabozantinib

Control arm

Active Comparator group

Description:

Subjects with advanced HCC will receive sorafenib 400 mg bid (twice a day)

Treatment:

Drug: Sorafenib

Single-Agent Cabozantinib arm

Other group

Description:

Subjects with advanced HCC will receive cabozantinib 60 mg qd

Treatment:

Drug: Cabozantinib

Drug: Cabozantinib