A Phase 3 clinical trial evaluating the immune checkpoint inhibitor Tyvyt (sintilimab injection), in combination with the chemotherapies Taxol (paclitaxel) and Platinol (cisplatin), as a first-line treatment for esophageal squamous cell carcinoma has started dosing patients.
The ORIENT-15 trial (NCT03748134), running in China, includes patients with locally advanced cancers who have failed prior treatments or whose disease has spread to distant organs and who cannot receive surgery for their disease. In total, 640 patients will be randomly assigned Tyvyt or a placebo, in combination with chemotherapy.
“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,” Lin Shen, MD, from the Beijing Cancer Hospital, said in a press release.
“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 III trial,” Shen added.
Tyvyt, jointly developed by Innovent Biologics and Eli Lilly and Company in China, is an antibody against PD-1, a protein found at the surface of immune T-cells.
Binding of PD-1 to the PD-L1 protein — produced by cancer cells — prevents the immune system from attacking cancer cells, allowing them to grow uncontrollably. By targeting PD-1 and blocking its interaction with PD-L1, Tyvyt is intended to boost anti-cancer immune responses.
The treatment is already approved in China for patients with classical Hodgkin’s lymphoma who failed two or more prior lines of chemotherapy.
ORIENT-15 was designed to determine if Tyvyt extends patients’ lives, either among the entire population and in those whose tumor cells produce the PD-L1 factor — a biomarker that usually predicts responses to PD-1/PD-L1 inhibitors. A secondary goal is to assess if the treatment also delays disease progression or death.
“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,” said Michael Yu, Innovent’s founder, CEO, and chairman.
“Based on the preliminary result of the ongoing phase II study, we have decided to conduct ORIENT-15, a phase III study as a first-line treatment for patients with esophageal squamous cell carcinoma. Our goal is to provide more effective cancer treatment options for these patients and for their families,” Yu added.
