Innovent phase 3 ORIENT-32 trial of Tyvyt in combo with Byvasda to treat advanced hepatocellular carcinoma meets primary endpoints

Innovent Biologics, a biopharmaceutical company, announced the results of a phase 3, open label, randomized study in China. The ORIENT-32 trial evaluating Tyvyt (sintilimab injection) in combination with Byvasda (bevacizumab biosimilar injection, or IBI305) as a first-line treatment in advanced hepatocellular carcinoma (HCC) met the predefined primary endpoints of progression-free survival (PFS) and overall survival (OS) in an interim analysis. This is the first phase 3 clinical trial using PD-1 inhibitor-based combination therapy that has met the primary endpoint in the first-line treatment of advanced HCC.

Based on the interim analysis conducted by the Independent Data Monitoring Committee (IDMC), Tyvyt (sintilimab injection) in combination with Byvasda (bevacizumab biosimilar injection) demonstrated a statistically significant improvement in PFS and OS compared with sorafenib. The safety profile of Tyvyt (sintilimab injection) and Byvasda (bevacizumab biosimilar injection) in this trial was consistent with previously reported studies, and no new safety signals were identified. These data will be presented at an upcoming medical conference. Based on the IDMC recommendation, Innovent will review these results with the Drug Evaluation Center (CDE) of the National Medical Products Administration (NMPA) in China.

The principal investigator of the ORIENT-32 study, Professor Fan Jia from Zhongshan Hospital of Fudan University, stated: “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, lenvatinib and chemotherapy are the main treatments for HCC in the first-line treatment setting in China, with very limited efficacy. 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 Tyvyt (sintilimab injection), in combination with Byvasda (bevacizumab biosimilar injection), can prolong PFS and OS in the first-line treatment of HCC. 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.”

Dr. Hui Zhou, vice president and head of oncology strategy and medical sciences of Innovent stated: “Tyvyt is the only anti-PD-1 monoclonal antibody included in the New Catalogue of the National Reimbursement Drug List in China. It was officially approved by the NMPA on December 24, 2018 for the treatment of relapsed or refractory classic Hodgkin’s lymphoma after two lines or later of systemic chemotherapy. Byvasda (bevacizumab biosimilar injection) was officially approved by the NMPA for patients with advanced non-small cell lung cancer and metastatic colorectal cancer in China. The results of the ORIENT-32 study demonstrate the potential of Tyvyt in combination with Byvasda to treat patients with advanced HCC in the first-line setting. We hope this clinical trial can potentially provide a more effective treatment option for clinicians and HCC patients. We would like to express our sincere gratitude to all the patients and investigators who participated in the ORIENT-32 study. Outstanding contributions were made through the joint efforts of investigators and the study team, despite the challenges and impact from the COVID-19 pandemic.

ORIENT-32 is a phase 3 randomized, open-label, multi-center study to evaluate the efficacy and safety of Tyvyt (sintilimab injection) in combination with Byvasda (bevacizumab biosimilar injection) compared to sorafenib in the first-line treatment of patients with advanced hepatocellular.

Enrolled patients were randomly assigned 2:1 to receive Tyvyt (sintilimab injection) combination with Byvasda (bevacizumab biosimilar injection) or sorafenib, until disease progression, unacceptable toxicity, withdrawal of consent, death, or other reasons stated in the protocol, whichever occurs first.

Primary liver cancer (PLC) is a common malignancy of the digestive system worldwide, among which about half new cases and deaths occur in China.

Tyvyt (sintilimab injection) is an innovative drug with global quality standards jointly developed by Innovent and Lilly in China. Tyvyt has been granted marketing approval by the NMPA for the treatment of relapsed or refractory classic Hodgkin’s lymphoma after two lines or later of systemic chemotherapy and was included in the 2019 Guidelines of Chinese Society of Clinical Oncology for Lymphoid Malignancies. Tyvyt is the only PD-1 inhibitor that has been included in the new Catalogue of the NRDL in November 2019.

Byvasda (IBI305) is a bevacizumab biosimilar and a recombinant humanized anti-VEGF monoclonal antibody drug. Vascular endothelial growth factor (VEGF) is an important factor in angiogenesis that is highly expressed by the endothelial cells in most human tumors. An anti-VEGF antibody binds VEGF selectively with high affinity and blocks its binding to VEGF receptors on the surface of vascular endothelial cells, thereby inhibiting signaling pathways such as PI3K-Akt/PKB and Ras-Raf-MEK-ERK. Byvasda produces anti-tumor effects by inhibiting the growth, proliferation and migration of vascular endothelial cells, blocking angiogenesis, reducing vascular permeability, blocking blood supply to tumor tissues, inhibiting the proliferation and metastasis of tumor cells and inducing apoptosis in tumor cells. Since the launch of bevacizumab, it has been approved for the treatment of patients with multiple malignant tumors globally, including non-small cell lung cancer, metastatic colorectal cancer, glioblastoma, renal cell carcinoma, cervical cancer, and epithelial ovarian, fallopian tube, or primary peritoneal cancer. The efficacy and safety of bevacizumab have been well recognized worldwide.