Date: 18-May-2020

Phase 2 Tyvyt ORIENT-2 Study Meets Primary Endpoint Of Overall Survival In Second-line Treatment Of Patients With Advanced/metastatic ESCC

Innovent Biologics, a world-class biopharmaceutical company that develops, manufactures and commercializes high-quality medicines for the treatment of cancer, autoimmune, metabolic and other major diseases, jointly announced with Eli Lilly and Company that the phase 2 Tyvyt (sintilimab injection) ORIENT-2 study in China met its primary endpoint of overall survival (OS).

The randomized study, which evaluated Tyvyt monotherapy compared to chemotherapy (paclitaxel or irinotecan) as a second-line treatment for patients with advanced or metastatic esophageal squamous cell carcinoma (ESCC), demonstrated a statistically significant improvement in OS. The safety profile of Tyvyt is consistent with previously reported Tyvyt study results, and no new safety signals were identified.

Innovent and Lilly plan to discuss these results with the Drug Evaluation Center (CDE) of the National Medical Products Administration (NMPA) in China.

The principal investigator of the ORIENT-2 study, Professor Jianming Xu from the Fifth Medical Center of the PLA General Hospital, stated: "The incidence of ESCC in Asian countries is much higher than that in Western countries. The current standard of treatment is still based on traditional chemotherapy and radiation therapy. Traditional chemotherapy drugs have shown a very limited effect on the second-line treatment of patients with advanced ESCC. Over the past 10 years, immunotherapy has made tremendous progress in multiple tumor types, but the drug development advancements in treating ESCC has been slower and there remains a huge unmet medical need. The ORIENT-2 study confirmed that Tyvyt can prolong overall survival in the second-line treatment of people with ESCC. We have seen that sintilimab is more efficacious than chemotherapy and we are hopeful that Tyvyt has the potential to be a new treatment option for these patients."

Dr. Hui Zhou, vice president and head of oncology strategy and medical sciences of Innovent, stated: “Tyvyt was approved by the NMPA in 2018 for the treatment of relapsed or refractory classic Hodgkin's lymphoma after second-line or later systemic chemotherapy. We currently have more than 20 clinical studies ongoing to evaluate the efficacy of Tyvyt in other types of tumors. The results of the ORIENT-2 study demonstrate the potential of Tyvyt to treat patients with advanced ESCC in the second-line setting. We are also conducting a phase 3 trial to evaluate Tyvyt combined with chemotherapy (paclitaxel and cisplatin) as a first-line treatment of patients with advanced, recurrent or metastatic ESCC. We hope these clinical trials can provide more effective treatment options for clinicians and benefit more ESCC patients. "

“From Hodgkin's lymphoma, lung cancer to esophageal cancer, we are glad to see that Tyvyt’s clinical efficacy has been demonstrated in multiple tumor types,” said Dr. Li Wang, senior vice president of Lilly China and Head of Lilly China Drug Development and Medical Affairs Center. “We are thankful to the patients and their families, investigators and clinical trial sites participating in the ORIENT-2 study, and to our colleagues from Innovent. We would not have seen these encouraging results without their efforts. We look forward to working to bring Tyvt as a new treatment option to people with ESCC in China.”

ORIENT-2 is a randomized, open-label, phase 2 study to evaluate the efficacy and safety of Tyvyt with paclitaxel or irinotecan in patients with advanced or metastatic ESCC who failed first-line treatment

A total of 190 subjects were enrolled in this study. They were randomly assigned 1:1 to receive Tyvyt or the investigator's choice of paclitaxel or irinotecan, until disease progression, unacceptable toxicity, withdrawal of consent, death, or other reasons stated in the protocol, whichever occurs first.

The incidence and mortality of esophageal cancer in China rank third and fourth, respectively. Squamous cell carcinoma accounts for approximately 90 percent of all esophageal cancer cases. A considerable proportion of patients with early-stage ESCC will develop recurrence or metastatic disease following resection surgery. Currently, the standard treatment for ESCC is limited to traditional chemotherapy and radiation therapy. There are few treatment options and no targeted therapies for ESCC, resulting in a large unmet clinical need.

Tyvyt (sintilimab injection), an innovative drug developed with global quality standards jointly developed by Innovent and Lilly in China, has been granted marketing approval by the NMPA for relapsed or refractory classic Hodgkin's lymphoma after second-line or later systemic chemotherapy, and included in the 2019 Guidelines of Chinese Society of Clinical Oncology for Lymphoid Malignancies. Tyvyt is the only PD-1 inhibitor that has been included in the new Catalogue of the National Reimbursement Drug List (NRDL), in November 2019. In April 2020, the NMPA accepted the supplemental new drug application for Tyvyt in combination with Alimta (pemetrexed) and platinum as first-line therapy in non-squamous non-small cell lung cancer (NSCLC). In May 2020, Tyvyt combined with Gemzar (gemcitabine for injection) and platinum chemotherapy met the predefined primary endpoint in the phase 3 ORIENT-12 study as first-line therapy in patients with locally advanced or metastatic squamous NSCLC.

Tyvyt is a type of 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 with Tyvyt to evaluate its safety and efficacy in a wide variety of cancer indications, including more than 10 registration or pivotal clinical trials.