On August 15, 2021 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 sintilimab Phase 3 ORIENT-16 study met its predefined primary endpoint of overall survival (OS) (Press release, Innovent Biologics, AUG 15, 2021, View Source [SID1234586587]). ORIENT-16 is a randomized, double-blind, multicenter Phase 3 clinical trial evaluating sintilimab in combination with chemotherapy (oxaliplatin and capecitabine) compared to chemotherapy alone in the first-line treatment of patients with unresectable, locally advanced, recurrent or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma.

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In an interim analysis, sintilimab in combination with chemotherapy demonstrated a statistically significant improvement in the primary endpoint of OS compared to placebo plus chemotherapy, in both the intention-to-treat (ITT) group and PD-L1 positive group. The safety profile of sintilimab in this study was consistent with that observed in previously reported studies of sintilimab, and no additional safety signals were identified for the combination of sintilimab and chemotherapy. These results will be presented at an upcoming medical meeting.

Based on the study’s Independent Data Monitoring Committee (IDMC) recommendation, Innovent plans to review these results and file a supplemental new drug application (sNDA) of sintilimab with the Drug Evaluation Center (CDE) of the National Medical Products Administration (NMPA) in China.

The principal investigator of the ORIENT-16 study, Prof. Jianming Xu from the Fifth Medical Center of People’s Liberation Army General Hospital, stated, "ORIENT-16 is the first Phase 3 clinical trial in China to demonstrate an anti-PD-1 antibody in combination with chemotherapy significantly prolonged overall survival in the first-line treatment of advanced gastric cancer. Gastric cancer is one of the most common malignant tumor types globally and nearly half of all cases are diagnosed in China. The prognosis of advanced gastric cancer is very poor. Currently, chemotherapy is the primary treatment option and targeted agents have offered limited benefit. The results of the ORIENT-16 study have the potential to bring a new and more effective treatment option to people with gastric cancer."

Dr. Zhou Hui, Senior Vice President of Clinical Development of Innovent, stated, "While immunotherapy has greatly changed the treatment paradigm for many malignancies, it has not yet in gastric cancer. The treatment options for advanced gastric cancer are very limited and the ORIENT-16 study aimed to help address this unmet medical need. These results are very encouraging and confirmed the clinical value of sintilimab plus chemotherapy in the first-line treatment of advanced gastric cancer. We are grateful for all the contributions made by every investigator and patient in this study, and we hope that sintilimab can become a treatment option for people with gastric cancer. Today, sintilimab is one of a few PD-1 inhibitors that has shown to be efficacious in the first-line treatment of five major types of cancer – nonsquamous non-small cell lung cancer, squamous non-small cell lung cancer, hepatocellular carcinoma, esophageal squamous cell carcinoma, and gastric cancer."

About the ORIENT-16 Study

ORIENT-16 is a randomized, double-blind, multicenter Phase 3 clinical study evaluating sintilimab in combination with chemotherapy (oxaliplatin and capecitabine), compared to placebo in combination with chemotherapy, for the first-line treatment of unresectable, locally advanced, recurrent or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma (ClinicalTrials.gov, NCT03745170). The primary endpoint was overall survival, in all randomized and in PD-L1 positive patients.

About Gastric Cancer

Gastric cancer is one of the most common malignant tumor types worldwide. According to GLOBOCAN estimates, there were approximately one million new cases and 769,000 new deaths of gastric cancer in 2020, making it the fifth most common cancer and third leading cause of cancer death globally. About half of all gastric cancer cases occurred in East Asia, mainly in China. Platinum-based chemotherapy is still the primary option in the first-line treatment of advanced gastric cancer. Currently, the 5-year survival rate of advanced or metastatic gastric cancer ranges from 5 to 20 percent, and the median overall survival is approximately one year.

About Sintilimab

Sintilimab, marketed as TYVYT (sintilimab injection) in China, is an innovative PD-1 inhibitor with global quality standards jointly developed by Innovent and Eli Lilly and Company. Sintilimab is an 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 of sintilimab to evaluate its safety and efficacy in a wide variety of cancer indications, including more than 10 registrational or pivotal clinical trials.

In China, sintilimab has been approved for four indications, including:

The treatment of relapsed or refractory classic Hodgkin’s lymphoma after two lines or later of systemic chemotherapy
In combination with pemetrexed and platinum chemotherapy, for the first-line treatment of nonsquamous non-small cell lung cancer
In combination with gemcitabine and platinum chemotherapy, for the first-line treatment of squamous non-small cell lung cancer
In combination with BYVASDA (bevacizumab biosimilar injection) for the first-line treatment of hepatocellular carcinoma
Additionally, Innovent currently has a regulatory submission under review in China for sintilimab for the second-line treatment of squamous non-small cell lung cancer.

Innovent also has three clinical studies of sintilimab that have met their primary endpoints:

In combination with cisplatin plus paclitaxel or cisplatin plus 5-fluorouracil for the first-line treatment of esophageal squamous cell carcinoma
In combination with oxaliplatin and capecitabine for the first-line treatment of unresectable, locally advanced, recurrent or metastatic gastric or gastroesophageal junction adenocarcinoma.
The second-line treatment of esophageal squamous cell carcinoma
In May 2021, the U.S. FDA accepted for review the Biologics License Application (BLA) for sintilimab in combination with pemetrexed and platinum chemotherapy for the first-line treatment of nonsquamous non-small cell lung cancer.

Sintilimab was included in China’s National Reimbursement Drug List (NRDL) in 2019 as the first PD-1 inhibitor and the only PD-1 included in the list in that year.