EA2205 – A Randomized Phase II Trial Evaluating Chemotherapy vs Chemotherapy plus Bevacizumab and Atezolizumab in Advanced Combined Hepatocellular Carcinoma-Cholangiocarcinoma

The study chair for this trial is David Hsieh, MD (UT Southwestern/Harold C. Simmons Comprehensive Cancer Center). The study co-chairs are Muhammad Beg, MD (also at UT Southwestern) and Xin Yao, MD (ThedaCare Regional Cancer Center).

Primary liver cancer is a rare disease with two types: hepatocellular carcinoma (90% of cases) and cholangiocarcinoma (cancer of the bile duct). Together, these cancers account for approximately 2% of all cancers in the US (about 41,260 cases annually). However, a few of these cases will include features of both cancer types—even rarer. Unfortunately, the prognosis for patients with combined hepatocellular carcinoma-cholangiocarcinoma (cHCC-CC) is poor. Further, researchers estimate that nearly half of all cHCC-CC cancers in the US are in the advanced stages when found and thus, cannot be removed by surgery.

To date, no standard of care exists for the treatment of advanced cHCC-CC, due to a lack of randomized trials for this particular disease. Additionally, trials examining HCC or CC usually exclude cHCC-CC. Therefore, patients with cHCC-CC require dedicated clinical trials to identify treatment strategies.

EA2205 is a randomized phase II trial investigating the efficacy of combined chemotherapy, immunotherapy, and anti-vascular endothelial growth factor (anti-VEGF) therapy (arm A) versus combined chemotherapy alone (arm B) in advanced cHCC-CC. Arm A will consist of atezolizumab, bevacizumab, gemcitabine, and cisplatin, while arm B will include gemcitabine and cisplatin. The study’s primary objective is to evaluate progression-free survival, defined as time to progressive disease or death due to any cause. Secondary objectives include evaluating objective response, defined as a complete or partial response, and evaluating overall response and disease control rate. The enrollment goal is 80 patients.

Preliminary studies demonstrated limited activity of both the chemotherapies typically used against CC and the therapies used for HCC. However, the results of a 2019 study in Asia suggest that combining HCC- and CC-specific treatments into a single therapeutic regimen has the potential to improve outcomes. In addition, other evidence outside of randomized clinical trials suggests that anti-VEGF therapy may be effective.

Regarding safety, the results from several studies support the safety of a combination regimen consistent with the distinct mechanisms of action and individual safety profiles of chemotherapy, anti-VEGF therapy, and anti-PD-L1 therapy.

Patients are eligible for this study if they have a confirmed diagnosis of cHCC-CC based on the 2019 WHO classification, including the classical type and intermediate cell carcinoma. Their cancer must be unresectable or metastatic, and they must not have any prior history of systemic therapy for cHCC-CC. They may be eligble if they have had prior locoregional therapy as long as certain criteria are met (available in the full protocol).

Learn more about EA2205 at ecog-acrin.org.