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.

Sex

All

Minimum age

18 Years

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.

• DERIVEDYau 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. PMID 38364832
• DERIVEDKelley 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. PMID 35798016
• DERIVEDKelley 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. PMID 32491932