Frontline sintilimab injection in combination with bevacizumab biosimilar injection resulted in a statistically significant improvement in progression-free survival and overall survival compared with sorafenib in patients with advanced hepatocellular carcinoma.
Frontline sintilimab injection (Tyvyt) in combination with bevacizumab biosimilar injection (Byvasda; IBI305) resulted in a statistically significant improvement in progression-free survival (PFS) and overall survival (OS) compared with sorafenib (Nexavar) in patients with advanced hepatocellular carcinoma (HCC), meeting the primary end points of the phase 3 ORIENT-32 trial.1
This is the first phase 3 trial examining a PD-1 inhibitor–based combination therapy to meet its primary end point in the frontline treatment of patients with advanced HCC, according to Innovent Biologics, Inc. The safety profile of the combination proved to be consistent with what has been reported in prior studies, with no new safety signals observed.
The data from the interim analysis will be presented at an upcoming medical meeting, according to the biopharmaceutical company. Moreover, the results are slated to be reviewed and discussed with the National Medical Products Administration (NMPA)’s Drug Evaluation Center.
“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 (Lenvima), and chemotherapy are the main treatments for HCC in the first-line treatment setting in China, with very limited efficacy,” said professor Fan Jia, PhD, Zhongshan Hospital of Fudan University, stated in a press release.
“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,” added Jia. “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 [patients with] HCC.”
Sintilimab injection is a kind of immunoglobulin G4 monoclonal antibody that was developed to bind to PD-1 molecules on the surface of T cells and to block the PD-1/PD-L1 pathway to reactivate T cells as way to eliminate cancer cells. IBI305 is a bevacizumab biosimilar and a recombinant humanized anti-VEGF monoclonal antibody drug.
In the open-label, multicenter, phase 3 trial, investigators set out to examine the safety and efficacy of sintilimab injection plus bevacizumab biosimilar injection versus sorafenib in the frontline treatment patients with advanced HCC.
To be eligible for participation, patients had to have HCC confirmed by either histology or cytology, an ECOG performance status of 0 or 1, no previous systemic antitumor treatment, have Barcelona Clinic Liver Cancer stage C, at least 1 measurable disease lesion at baseline per RECIST v1.1 criteria, and acceptable organ and bone marrow function.2
If patients had fibrous lamellar HCC, sarcomatoid disease, or cholangiocarcinoma components in the tumor tissue, they were not permitted. If they had a history of hepatic encephalopathy or a history of liver transplantation they were not included. Moreover, any patients who exhibited clinical symptoms requiring drainage of pleural effusion, ascites, or pericardial effusion, they could not participate. Patients with central nervous system metastasis, uncontrolled high blood pressure, and who received local treatment for liver lesions within 4 weeks, were also ineligible for inclusion on the trial.
The primary end points of the trial were OS and PFS per RECIST v1.1 criteria and independent radiological review committee. Secondary end points of the trial included PFS per RECIST v1.1 criteria and investigator assessment, objective response rate, disease control rate, time to progression, time to response, and duration of response, among others.
In the trial, participants were randomized 2:1 to receive either the sintilimab injection at a dose of 200 mg on day 1 every 3 weeks plus bevacizumab biosimilar injection at a dose of 15 mg/kg on day 1 every 3 weeks, or sorafenib. Patients received treatment until either progressive disease, intolerable toxicity, withdrawn consent, death, or other reasons stated in the trial protocol, whichever occurred first.
“[Sintilimab injection] 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 4, 2018 for the treatment of relapsed or refractory classic Hodgkin lymphoma after 2 lines or later of systemic chemotherapy,” Hui Zhou, PhD, vice president and head of Oncology Strategy and Medical Sciences at Innovent, added in the release. “[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 [sintilimab injection] in combination with [bevacizumab biosimilar injection] to treat patients with advanced HCC in the first-line setting.”