Innovent Announces the Phase 3 ORIENT-16 Study Results Published in JAMA Evaluating Sintilimab in Combination with Chemotherapy for the First-Line Treatment of Gastric or Gastroesophageal Junction...

ROCKVILLE, Md. and SUZHOU, China, Dec. 5, 2023 /PRNewswire/ -- Innovent Biologics, Inc. ("Innovent") (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high quality medicines for the treatment of oncology, autoimmune, metabolic, ophthalmology and other major diseases, announced the interim analysis results of ORIENT-16, the Phase 3 study evaluating sintilimab in combination with chemotherapy compared to chemotherapy for the first-line treatment of advanced or metastatic gastric or gastroesophageal junction (G/GEJ) adenocarcinoma was published in The Journal of the American Medical Association (JAMA, IF=120.7). ORIENT-16 the first immunotherapy Phase 3 study published in JAMA for the first-line treatment of gastric cancer, as well as the first immunotherapy Phase 3 in Chinese patients for the first-line treatment of gastric cancer.

Gastric cancer is one of the most common malignant tumor types globally and nearly half of all cases are diagnosed in China[i]. Advanced gastric cancer generally has very poor prognosis with high unmet medical need. ORIENT-16 demonstrated that sintilimab plus chemotherapy significantly prolongs overall survival in the first line treatment for overall population of gastric cancer. Based on the results of ORIENT-16, sintilimab is recommended by the Chinese Society of Clinical Oncology (CSCO) guidelines for the first-line treatment of gastric cancer. It is also the first and only PD-1 inhibitor included in national reimbursement drug list (NRDL) for the first-line treatment of gastric cancer.

ORIENT-16 has met its primary endpoint at the prespecified interim analysis. Sintilimab in combination with chemotherapy demonstrated superior and clinical meaningful overall survival (OS) benefit, compared with placebo plus chemotherapy in all randomized patients as well as patients with CPS ≥5 . Detailed interim analysis results were published in JAMA.

• Interim analysis (cut-off date June 20, 2021, median follow-up 18.8 month) showed that, sintilimab in combination with chemotherapy significantly reduced the risk of death in all randomized patients (HR 0.77, 95%CI 0.63-0.94, p=0.009) and in patients with CPS ≥5 (HR 0.66, 95%CI 0.50-0.86, p=0.002) , successfully reached the prespecified superiority criteria. Median overall survival (mOS) has been prolonged by 2.9months (mOS 15.2mo vs. 12.3mo) in all randomized patients, and 5.5 months (mOS 18.4mo vs. 12.9mo) in patients with CPS ≥5, respectively. In addition, OS benefits were consistent in all prespecified subgroups. 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 in GC patients.

Furthermore, prespecified final analysis results of ORIENT-16 has been published at the AACR (American Association for Cancer Research) Annual Meeting. Final analysis (with additional 15-month follow-up) indicated that OS benefits of sintilimab plus chemotherapy have become more evident in overall population and in patients with CPS ≥5 compared with that of interim analysis, further confirming sintilimab plus chemotherapy as a standard of care of 1L treatment for G/GEJ adenocarcinoma.

• Final analysis (cut-off date September 2, 2022, median follow-up 33.9 mo) showed that, sintilimab in combination with chemotherapy significantly reduced the risk of death in all randomized patients (HR 0.68, 95% CI: 0.57-0.81; P<0.0001) as well as in patients with CPS ≥5 (HR 0.59, 95% CI: 0.47-0.74; P<0.0001) . Median overall survival (mOS) has been prolonged by 2.9months (mOS 15.2mo vs. 12.3mo) in all randomized patients and by 6.3 months (mOS 19.2mo vs. 12.9mo) in patients with CPS ≥5, respectively. OS benefits were consistent in all prespecified subgroup analyses. The overall safety profile of final analysis was consistent with that observed in previously reported interim analysis, and no additional safety signals were identified with additional 15-month follow-up.

Based on the study results of ORIENT-16, sintilimab in combination with chemotherapy was approved by the National Medical Products Administration (NMPA) of China as first-line treatment for G/GEJ in June 2022, and was included in the national reimbursement drug list (NRDL), becoming the first and only immunotherapy for gastric cancer covered by NRDL 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 trial in China to demonstrate a significant overall survival benefit in patients with advanced G/GEJ cancer treated with anti-PD-1 antibody plus chemotherapy in first line setting. The study has met its primary endpoint in the prespecified interim result analysis, and its final analysis demonstrated the OS benefit of sintilimab plus chemotherapy in overall population and in patients with CPS ≥5 compared with chemotherapy alone. ORIENT-16 confirms sintilimab plus chemotherapy as an important new treatment option and a standard of care of first line treatment for G/GEJ adenocarcinoma."

Dr. Zhou Hui, Senior Vice President of Innovent, stated, "The treatment options for advanced G/GEJ cancer are relatively limited and the ORIENT-16 study aimed to address this urgent unmet medical need. ORIENT-16 is the first randomized controlled Phase 3 study in China to demonstrate that PD-1 in combination with chemotherapy significantly prolongs overall survival in overall population of first line treatment for G/GEJ adenocarcinoma. The publication in JAMA further confirms its huge clinical value of the ORIENT-16 study. We are grateful for all the contributions made by every investigator and patient in this study. Up until now, sintilimab is the only PD-1 inhibitor in China approved and included in NRDL for the first-line treatment of five major types of cancer – non-squamous non-small cell lung cancer, squamous non-small cell lung cancer, hepatocellular carcinoma, esophageal squamous cell carcinoma, and gastric cancer. Sintilimab is also the first and only immunotherapy for gastric cancer covered by NRDL. We hope this novel immunotherapy to benefit a wider group of cancer patients."

About the ORIENT-16 Study

ORIENT-16 is a randomized, double-blind, multicenter Phase 3 clinical study evaluating sintilimab in combination with chemotherapy, 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^i[ii]. About half of all gastric cancer cases occurred in East Asia, mainly in Chinaⁱ. The first-line treatment of advanced gastric cancer remains limited. Currently, the 5-year survival rate of advanced or metastatic gastric cancer ranges from 5 to 20 percent. The median survival was about 1 year for patients who received chemotherapy only[iii][iv].

About Sintilimab

Sintilimab, marketed as TYVYT® (sintilimab injection) in China, is a PD-1 immunoglobulin G4 monoclonal antibody co-developed by Innovent and Eli Lilly and Company. Sintilimab 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[v]. 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 seven indications and included in the National Reimbursement Drug List (NRDL) for six indications. The updated NRDL reimbursement scope of TYVYT® (sintilimab injection) include:

• For the treatment of unresectable locally advanced, recurrent or metastatic gastric or gastroesophageal junction adenocarcinoma;
• For the treatment of unresectable locally advanced, recurrent or metastatic esophageal squamous cell carcinoma;
• For the treatment of unresectable locally advanced or metastatic non-squamous non-small cell lung cancer lacking EGFR or ALK driver gene mutations;
• For the treatment of unresectable locally advanced or metastatic squamous non-small cell lung cancer;
• For the treatment of unresectable or metastatic hepatocellular carcinoma with no prior systematic treatment;
• For the treatment of relapsed or refractory classic Hodgkin's lymphoma after two lines or later of systemic chemotherapy.

Additionally, sintilimab has been approved in combination with bevacizumab and chemotherapy (pemetrexed and cisplatin) for the treatment of patients with EGFR-mutated nsqNSCLC who progressed after EGFR-TKI therapy.

Besides, two clinical studies of sintilimab have met their primary endpoints:

• Phase 2 study of sintilimab monotherapy as second-line treatment of esophageal squamous cell carcinoma;
• Phase 3 study of sintilimab monotherapy as second-line treatment for squamous NSCLC with disease progression following platinum-based chemotherapy.

Statement: Innovent does not recommend the use of any unapproved drugs/indications.

About Innovent

Inspired by the spirit of "Start with Integrity, Succeed through Action," Innovent's mission is to discover and develop, manufacture and commercialize high-quality biopharmaceutical products that are affordable to ordinary people. Established in 2011, Innovent is committed to discovering and developing, manufacturing and commercializing high-quality innovative medicines for the treatment of oncology, autoimmune, cardiovascular and metabolic, and ophthalmology diseases to enhance the quality of the patients' lives. Innovent has 10 products in the market, including TYVYT® (Sintilimab Injection), BYVASDA® (Bevacizumab Injection), SULINNO® (Adalimumab Injection), HALPRYZA® (Rituximab Injection), Pemazyre® (Pemigatinib Oral Inhibitor), olverembatinib, Cyramza® (Ramucirumab Injection), Retsevmo® (Selpercatinib Capsules ), FUCASO® (Equecabtagene  Autoleucel Injection) and SINTBILO® (Tafolecimab Injection). Additionally, we have 2 NDA under NMPA review, 5 assets in Phase III or pivotal clinical trials, and 19 more molecules in early clinical stage.

Innovent has also entered into 30 strategic collaborations with Eli Lilly, Roche, Sanofi, Adimab, Incyte, MD Anderson Cancer Center and other international partners. We strive to work with many collaborators to help advance the biopharmaceutical industry, improve drug availability and enhance the quality of the patients' lives.

Note:

TYVYT® (sintilimab injection) is not an approved product in the United States.
BYVASDA® (bevacizumab biosimilar injection), SULINNO®, and HALPRYZA® (rituximab biosimilar injection) are not approved products in the United States.
TYVYT® (sintilimab injection, Innovent)
BYVASDA® (bevacizumab biosimilar injection, Innovent)
HALPRYZA® (rituximab biosimilar injection, Innovent)
SULINNO® (adalimumab biosimilar injection, Innovent)
Pemazyre® (pemigatinib oral inhibitor, Incyte Corporation). Pemazyre® was discovered by Incyte Corporation and licensed to Innovent for development and commercialization in Mainland China, Hong Kong, Macau and Taiwan.
CYRAMZA® (ramucirumab, Eli Lilly). Cyramza® was discovered by Eli Lilly and licensed to Innovent for commercialization in Mainland China.
Retsevmo® (selpercatinib, Eli Lilly). Retsevmo® was discovered by Eli Lilly and licensed to Innovent for commercialization in Mainland China.

Disclaimer: Innovent does not recommend any off-label usage.

Forward-Looking Statements

This news release may contain certain forward-looking statements that are, by their nature, subject to significant risks and uncertainties. The words "anticipate", "believe", "estimate", "expect", "intend" and similar expressions, as they relate to Innovent, are intended to identify certain of such forward-looking statements. Innovent does not intend to update these forward-looking statements regularly.

These forward-looking statements are based on the existing beliefs, assumptions, expectations, estimates, projections and understandings of the management of Innovent with respect to future events at the time these statements are made. These statements are not a guarantee of future developments and are subject to risks, uncertainties and other factors, some of which are beyond Innovent's control and are difficult to predict. Consequently, actual results may differ materially from information contained in the forward-looking statements as a result of future changes or developments in our business, Innovent's competitive environment and political, economic, legal and social conditions.

Innovent, the Directors and the employees of Innovent assume (a) no obligation to correct or update the forward-looking statements contained in this site; and (b) no liability in the event that any of the forward-looking statements does not materialize or turn out to be incorrect.

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