Phase 3 ORIENT-32 Trial Shows Promise for First-Line Treatment Combo in HCC

The study is evaluating the efficacy and safety of sintilimab injection in combination with bevacizumab biosimilar injection compared to sorafenib in the first-line treatment of patients with advanced hepatocellular carcinoma.

The open-label, randomized, phase 3 ORIENT-32 trial, evaluating sintilimab injection (Tyvyt) in combination with bevacizumab biosimilar injection (Byvasda or IBI305) as a first-line treatment for patients with advanced hepatocellular carcinoma (HCC), met its predefined primary end points of progression-free survival (PFS) and overall survival (OS) in an interim analysis, according to Innovent Biologics, the developer of the agents.

Importantly, this is the first phase 3 clinical trial using a PD-1 inhibitor-based combination therapy that has met its primary end point in the first-line treatment of advanced HCC.

"In China, HCC is the fourth most common malignancy with the second highest mortality rate. More than half of new and fatal cases of HCC in the world occur in China every year. At present, sorafenib (Nexavar), lenvatinib (Lenvima), and chemotherapy are the main treatments for HCC in the first-line treatment setting in China, with very limited efficacy,” principle investigator of the study, Fan Jia, PhD, from the Zhongshan Hospital of Fudan University, said in a press release. “About 85% of HCC patients in China have the history of HBV infection, which is a quite different feature from HCC in the European and American countries. Therefore, continued clinical research in treating HCC is of great importance in China.”

“The ORIENT-32 study confirmed that [sintilimab injection], in combination with [bevacizumab biosimilar injection], can prolong PFS and OS in the first-line treatment of HCC,” Jia continued. “Despite the COVID-19 pandemic, all study investigators worked to overcome many challenges to continue this trial with the goal of bringing new hope to HCC patients."

The ORIENT-32 study is designed to evaluate the efficacy and safety of sintilimab injection in combination with bevacizumab biosimilar injection compared to sorafenib in the first-line treatment of patients with advanced HCC (NCT 03794440). The dual primary end points are PFS and OS assessed by Independent Radiographic Review Committee (IRRC) based on RECIST v1.1.

Patients enrolled in the study were randomly assigned 2:1 to receive either the sintilimab injection combination with bevacizumab biosimilar injection or sorafenib until disease progression, unacceptable toxicity, withdrawal of consent, death, or other reasons stated in the protocol, whichever occurs first. The study is being conducted in China.

Based on the interim analysis conducted by the Independent Data Monitoring Committee (IDMC), sintilimab injection in combination with bevacizumab biosimilar injection demonstrated a statistically significant improvement in PFS and OS compared with sorafenib. Further, the safety profile of the sintilimab injection and bevacizumab biosimilar injection combination in this trial was consistent with that reported previously, and no new safety signals were identified.

These data will be presented at an upcoming medical conference. Based on a recommendation provided by the IDMC, Innovent indicated it will also review these results with the Drug Evaluation Center (CDE) of the National Medical Products Administration (NMPA) in China.

TYVYT® (Sintilimab Injection) in Combination with BYVASDA® (Bevacizumab Injection) ORIENT-32 Study Met Its Primary Endpoints of Progression-Free Survival and Overall Survival in the First-Line Tre... [news release]. San Francisco and Suzhou, China. Published September 28, 2020. Accessed September 28, 2020.

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