SUZHOU, China—Innovent Biologics, Inc. announced today that the first patient has been dosed in a Phase 3 clinical trial (ORIENT-15) that is to evaluate Tyvyt (fully human anti-PD-1 therapeutic monoclonal antibody, generic name: sintilimab injection), in combination with paclitaxel and cisplatin, as first-line treatment in patients with advanced, recurrent or metastatic esophageal squamous cell carcinoma (ESCC).
Tyvyt is a type of immunoglobulin G4 monoclonal antibody, which binds to the PD-1 molecule on the surface of T-cells, blocks the PD-L1 (Programmed Cell Death-1 Ligand-1, PD-L1 pathway) and reactivates T-cells to kill cancer cells. Tyvyt is the only PD-1 antibody in China branded by both a local biopharmaceutical company and a global pharmaceutical company. Tyvyt was jointly developed by Innovent and Eli Lilly and Company.
“The incidence of esophageal squamous cell carcinoma in Asian countries is much higher than in western countries. Today, patients have no treatment options other than chemotherapy and radiation therapy. Immune checkpoint inhibitors have brought new hope to patients with this life-threatening disease. Based on the efficacy signals and the safety profile from previous trials, we hope to validate the therapeutic potential of Tyvyt (sintilimab injection) in combination with chemotherapy in ORIENT-15, a Phase 3 trial,” said Professor Lin Shen from the Beijing Cancer Hospital.
The ORIENT-15 study is a randomized, double-blind, multi-center, Phase 3 trial that evaluates the efficacy and safety of Tyvyt (sintilimab injection) or placebo in combination with chemotherapy as first-line treatment in subjects with unresectable, locally advanced, recurrent or metastatic ESCC. The phase III study will enroll 640 patients.
Patients will receive Tyvyt (sintilimab injection) or placebo in combination with paclitaxel and cisplatin until disease progression. Participants will be randomly assigned in a 1:1 ratio into experimental or control groups. The primary endpoint is overall survival in both the entire population and in PD-L1 positive population of patients. The study follows a Phase 1b study that evaluated Tyvyt (sintilimab injection) in patients with esophageal cancer and a Phase 2 study that evaluated Tyvyt (sintilimab injection) versus paclitaxel/irinotecan as second-line therapy for patients with advanced/metastatic ESCC.
Esophageal cancer is the eighth most common cancer in the world, and the sixth leading cause of cancer death. Nearly four out of five cases occur in developing countries. China has the largest population of patients with esophageal cancer in the world. The incidence and mortality in China are higher than the worldwide average, ranking 3rd and 4th respectively. The histopathological type of esophageal cancer in China is different than that in Europe and the United States. In China the major type of esophageal cancer is squamous cell carcinoma which accounts for more than 90% of cases. In the United States and Europe, adenocarcinoma of the esophagus is the predominant histopathology. The prognosis of patients with advanced and metastatic esophageal cancer is poor, with an overall survival of about 10 months.
“Esophageal cancer is the third most common malignant tumor in China. The development of new agents for the treatment of advanced esophageal squamous cell carcinoma has been stagnant, so there is a huge unmet medical need. Based on the preliminary result or the ongoing Phase 2 study, we have decided to conduct ORIENT-15, a Phase 3 study as a first-line treatment for patients with esophageal squamous cell carcinoma,” added Michael Yu, Founder, Chief Executive Officer and Chairman of Innovent. “Our goal is to provide more effective cancer treatment options for these patients and for their families.”