IV Sintilimab and Bevacizumab Biosimilar Improve Survival in Frontline Advanced HCC

The sintilimab injection (Tyvyt) in combination with IBI305 (Byvasda), a biosimilar to bevacizumab (Avastin), improved overall survival (OS) as well as progression-free survival (PFS) compared with sorafenib (Nexavar) as frontline treatment of patients with advanced hepatocellular carcinoma (HCC), meeting the predefined primary end point of the phase 3 ORIENT-32 clinical trial (NCT03794440). Results were reported in a press release from Innovent Biologics, Inc., the manufacturer of the agent.

An Independent Data Monitoring Committee determined that the improvements in OS and PFS were statistically significant during an interim analysis of the trial. Additionally, the safety profiles of both sintilimab for injection and IBI305 were consistent with prior studies with no new safety signals observed. Data from ORIENT-32 will be presented at an upcoming medical conference

“The ORIENT-32 study confirmed that Tyvyt, in combination with Byvasda, 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 [patients with HCC],” Fan Jia, PhD, professor at Zhongshan Hospital of Fudan University in Shanghai, China, and principal investigator of the study, said in a statement.

ORIENT-32 in a randomized, open-label, multicenter study of approximately 566 patients. The goal of the study is to evaluate the efficacy and safety of the sintilimab injection combined with IBI305 versus sorafenib in front-line setting of advanced HCC. Patients in the ongoing study are randomized 2:1 to receive intravenous (IV) sintilimab 200 mg with IBI305 15 mg/kg given once every 3 weeks in the experimental arm or sorafenib 400 mg orally twice per day. All patients received therapy until disease progression, unacceptable toxicity, withdrawal of consent, or death.

In addition the co primary end points of PFS and OS, the secondary end points being explored in the study include: investigator-assessed PFS per RECIST v1.1, objective response rate, disease control rate, duration of response, time to progression, and time to response.

Histologically or cytologically confirmed advanced HCC was a key requirement for patients to enroll in the study. It was also required that patients have an ECOG performance status of 0 or 1, be naïve to systemic antitumor therapy, be done with postoperative adjuvant chemotherapy for more than 6 months, have Barcelona Clinic Liver Cancer stage C or B, have at least 1 lesion with measurable disease at baseline per RECIST v1.1, have a Child-Pugh score of at least 7, and have adequate bone marrow and organ function.

The presence of fibrous lamellar HCC, sarcomatoid HCC, and cholangiocarcinoma components in tumor tissues were grounds for exclusion from the study. Other exclusion criteria include a history of hepatic encephalopathy or liver transplantation, central nervous system metastasis, uncontrolled blood pressure, and local treatment for liver lesion within 4 weeks.

Both IV sintilimab and IBI305 have gained regulatory traction in China. IV sintilimab is approved in China and a supplemental new drug application was submitted for the dug in combination with pemetrexed and platinum-based chemotherapy as first-line treatment ofpatients with nonsquamous non–small cell lung cancer (NSCLC). Injectable sintilimab in combination with other agents has also demonstrated promise in clinical trials like the phase 3 ORIENT-12 study (NCT03629925) and the ORIENT-2 (NCT03116152) study.

IBI305 is known to block VEGF similarly to bevacizumab, a drug that has indications in multiple malignant tumors globally, including NSCLC; metastatic colorectal cancer; glioblastoma; renal cell carcinoma; cervical cancer; and epithelial ovarian, fallopian tube, or primary peritoneal cancer.

“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,” stated Hui Zhiu, vice president and head of Oncology Strategy and Medical Sciences of Innovent.

_Reference:

_{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 treatment of patients with advanced hepatocellular carcinoma (HCC). News release. Innovent Biologics, Inc. September 28, 2020. Accessed September 28, 2020.}