Byvasda Shines in Combination With PD-1 Inhibitor

In a phase 3 study conducted by Innovent Biologics, a combination therapy consisting of biosimilar bevacizumab (Byvasda) and sintilimab (Tyvyt) injection, a programmed death-1 (PD-1) inhibitor, met the trial’s predefined primary end points, according to an interim analysis.

The randomized, open-label, multicenter ORIENT-32 study evaluated the safety and efficacy of sintilimab in combination with Byvasda in patients with advanced hepatocellular carcinoma (HHC), the most common form of liver cancer, accounting for 85% to 90% of liver cancer cases worldwide.

The combination demonstrated a statistically significant improvement in progression-free survival and overall survival compared with sorafenib (Nexavar).

"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,” Hui Zhou, PhD, vice president and head of oncology strategy and medical sciences at Innovent, said in a statement.

According to the study lead author, Fan Jia, PhD, president of Zhongshan Hospital at Fudan University in Shanghai, China, HHC is the fourth most common malignancy and has the second highest mortality rate in China. More than half of the world’s HHC cases and deaths occur in China annually, where it is largely caused by hepatitis B virus and/or hepatitis C virus infection, according to Innovent.

“About 85% of HCC patients in China have the history of hepatitis B 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,” Jia said.

More on the Trial

This was the first phase 3 clinical trial to assess the use of a PD-1 inhibitor in combination therapy that has met the primary end point in the first-line treatment of advanced HHC, according to Innovent.

Patients were randomly assigned 2:1 to receive sintilimab in combination with Byvasda or sorafenib as part of first-line treatment until the patients experienced disease progression or unacceptable toxicity.

The ORIENT-32 trial results were consistent with previously reported studies and no new safety signals were identified for Byvasda or sintilimab.

Specifics of the data from the ORIENT-32 clinical trial will be presented at an upcoming medical conference. As part of IDMC’s recommendations, Innovent will review the trial results with the Drug Evaluation Center of China’s National Medical Products Administration (NMPA).

Byvasda, Tyvyt and PD-1 Inhibitors

Byvasda is a recombinant humanized anti–vascular endothelial growth factor monoclonal antibody biosimilar referencing Genentech’s Avastin. It was approved by the NMPA for marketing in June 2020 for the treatment of advanced non–small cell lung cancer (NSCLC) and metastatic colorectal cancer.

Sintilimab, developed as part of a partnership between Innovent and Eli Lilly, was granted marketing approval by the NMPA in 2018 for the treatment of relapsed or refractory classic Hodgkin's lymphoma after at least second-line system chemotherapy.

In 2020, a phase 3 trial of sintilimab in combination with pemetrexed (Alimta) and platinum demonstrated statistically significant improvement in progression-free survival in patients with advanced or recurrent nonsquamous NSCLC.

PD-1 inhibitors are targeted therapies in cancer that function by blocking PD-1/PD-1 ligand interaction to allow the cell-signaling process to alert the immune system to attack and destroy cancer cells.

PD-1 inhibitors are gaining traction in the biosimilar development world. In September 2020, NeuClone announced that it is developing 2 biosimilars for blockbuster PD-1 inhibitors, including nivolumab (Opdivo) and pembrolizumab (Keytruda), which are both used to treat melanoma, lung cancer, head and neck cancer, Hodgkin lymphoma, stomach cancer, liver cancer, and gastric cancers.