On November 20, 2020 Innovent Biologics, Inc. ("Innovent") (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high-quality medicines for the treatment of oncology, metabolic, autoimmune and other major diseases, reported that the results of the Phase 3 ORIENT-32 study were released in a late-breaking proffered oral presentation at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) Asia ("ESMO Asia") Virtual Congress 2020 (Press release, Innovent Biologics, NOV 22, 2020, View Source [SID1234571528]).
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ORIENT-32 is the first randomized Phase 3 study reporting the efficacy and safety of an anti-PD-1 antibody-based combination therapy versus sorafenib as the first-line treatment in patients with advanced unresectable hepatocellular carcinoma (HCC). A total of 571 patients were enrolled in the trial. Based on an interim analysis conducted by the study’s Independent Data Monitoring Committee (IDMC), TYVYT (sintilimab injection) in combination with BYVASDA (bevacizumab biosimilar injection) demonstrated significantly improved overall survival (OS) and Independent Radiographic Review Committee (IRRC) progression-free survival (PFS) versus sorafenib. Compared to sorafenib, TYVYT (sintilimab injection) plus BYVASDA (bevacizumab biosimilar injection) demonstrated a 43.1% decreased risk of all-cause mortality (HR 0.569, 95%CI: 0.431-0.751, P<0.0001); the median OS was not reached in the TYVYT (sintilimab injection) plus BYVASDA (bevacizumab biosimilar injection) arm versus 10.4 months in the sorafenib arm. TYVYT (sintilimab injection) plus BYVASDA (bevacizumab biosimilar injection) also demonstrated 43.5% decreased risk of progression as assessed by IRRC (HR 0.565 95%CI: 0.455-0.701, P<0.0001); median PFS was 4.6 months in the TYVYT (sintilimab injection) plus BYVASDA (bevacizumab biosimilar injection) arm versus 2.8 months in the sorafenib arm.
The significantly improved OS and PFS benefits brought by TYVYT (sintilimab injection) plus BYVASDA (bevacizumab biosimilar injection) over sorafenib were generally consistent across all subgroups. The combination regimen showed an acceptable safety profile with no new safety signals. With these results, TYVYT (sintilimab injection) plus BYVASDA (bevacizumab biosimilar injection) could potentially provide a new option for the first-line treatment of patients with advanced HCC.
Dr. Hui Zhou, Vice President and Head of Oncology Strategy and Medical Sciences of Innovent, 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. Despite the challenges and impact from the COVID-19 pandemic, the ORIENT-32 study was carried out smoothly and successfully under the joint efforts of all investigators and patients with their families. We are very pleased to see that the ORIENT-32 study demonstrated significant prolongation of OS and PFS in advanced HCC patients in China. With these encouraging results，we will apply to the National Medical Products Administration for the new drug application of TYVYT (sintilimab injection) in combination with BYVASDA (bevacizumab biosimilar injection). We look forward to this potentially becoming a new treatment regimen that could help more patients with HCC to live longer without their disease worsening."
About ORIENT-32 Trial
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 carcinoma（ClinicalTrials.gov, NCT 03794440）. The primary endpoints of the trial are overall survival (OS) and progression-free survival (PFS) as assessed by Independent Radiographic Review Committee (IRRC) based on RECIST v1.1.
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.
About Hepatocellular Carcinoma (HCC)
Primary liver cancer（PLC）is a common malignancy of the digestive system worldwide, among which about half new cases and deaths occur in China. The main pathological types of liver cancer are hepatocellular carcinoma (HCC), accounting for 85 to 90 percent, and a small number of cases of intrahepatic cholangiocarcinoma（ICC） and HCC-ICC mixed liver cancer. In China, HCC is primarily caused by hepatitis B virus (HBV) and/or hepatitis C virus (HCV) infection.
About TYVYT (Sintilimab Injection)
TYVYT (sintilimab injection), an innovative drug with global quality standards jointly developed in China by Innovent and Lilly, 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 included in the 2019 Guidelines of Chinese Society of Clinical Oncology for Lymphoid Malignancies. TYVYT (sintilimab injection) is the only PD-1 inhibitor included in the new Catalogue of the National Reimbursement Drug List (NRDL). In April 2020, the NMPA accepted the sNDA for TYVYT (sintilimab injection) in combination with ALIMTA (pemetrexed) and platinum chemotherapy as first-line therapy for the treatment of patients with nonsquamous non-small cell lung cancer (NSCLC). In May 2020, TYVYT (sintilimab injection) monotherapy met the primary endpoint of overall survival in the Phase 2 ORIENT-2 study as second-line therapy in patients with advanced or metastatic esophageal squamous cell carcinoma. In August 2020, the NMPA accepted the sNDA for TYVYT (sintilimab injection) in combination with GEMZAR (gemcitabine for injection) and platinum chemotherapy as first-line therapy in squamous NSCLC. In September 2020, TYVYT (sintilimab injection) in combination with BYVASDA (bevacizumab biosimilar injection) as a first-line treatment in advanced hepatocellular carcinoma met the predefined primary endpoints of overall survival and progression-free survival in an interim analysis of the Phase 3 ORIENT-32 study.
TYVYT (sintilimab injection) is a fully human immunoglobulin G4 monoclonal antibody, which binds to PD-1 molecules on the surface of T-cells, blocks the PD-1 / PD-Ligand 1 (PD-L1) pathway and reactivates T-cells to kill cancer cells. Innovent is currently conducting more than 20 clinical studies for TYVYT (sintilimab injection) to evaluate its safety and efficacy in a wide variety of cancer indications, including more than 10 registrational or pivotal clinical trials. This includes global clinical research studies on TYVYT (sintilimab injection).
About BYVASDA (Bevacizumab Biosimilar Injection)
BYVASDA 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.