Innovent Releases Final Analysis Results of ORIENT-16: the Phase 3 Study of Sintilimab in Combination with Chemotherapy for the First-Line Treatment of Gastric Cancer at the AACR Annual Meeting 2023

ROCKVILLE, Md. and SUZHOU, China, April 17, 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 final 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) cancer at the American Association for Cancer Research (AACR) Annual Meeting 2023 (Abstract CT078).

As of data cutoff date (September 2, 2022), a total of 650 patients were randomly assigned and received treatment, and the median follow-up was 33.9 months.

• Sintilimab in combination with chemotherapy continuously demonstrated superior overall survival (OS) compared to placebo plus chemotherapy with a 41.3% reduction in the risk of death (HR 0.587 [95% CI: 0.467, 0.738]; P<0.0001) and a 6.3-month improvement in median OS (19.2 months vs. 12.9 months) in patients with CPS ≥5, and 31.9% reduction in the risk of death (HR 0.681 [95% CI: 0.571, 0.812]; P<0.0001）and a 2.9-month improvement in mOS (15.2 months vs. 12.3 months) in all randomized patients.
• In all randomized patients, the estimated OS rates at 2-year and 3-year for sintilimab plus chemotherapy vs chemotherapy were 37.6% vs 20.6% and 26.0% vs 10.7%, respectively. In patients with CPS≥5, the estimated OS rates at 2-year and 3-year for sintilimab plus chemotherapy vs chemotherapy were 43.6% vs 22.0% and 29.0% vs 10.7%, respectively. In addition, OS benefits were consistent in all prespecified subgroup analyses.
• The safety profile of this 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.

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. Sintilimab has been approved by National Medical Products Administration (NMPA) in China as the first line treatment for patients with advanced G/GEJ adenocarcinoma and this new indication has been included in the updated National Reimbursement Drug List (2022 Version), making it the first and only PD-1 inhibitor for gastric cancer included in the NRDL. This final analysis showed OS benefit of sintilimab plus chemotherapy was more evident in overall population and in patients with CPS ≥5 compared with that of interim analysis, further confirming sintilimab plus chemotharapy as a standard of care of first line treatment for G/GEJ adenocarcinoma. 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. Approval and inclusion into the updated NRDL of sintilimab plus chemotherapy as first line standard of care for G/GEJ adenocarcinoma has bring an important new treatment option to patients with G/GEJ cancer."

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. Both interim and final analysis results have consistently demonstrated the significant clinical benefit of sintilimab plus chemotherapy as first-line treatment of advanced G/GEJ cancer.  And we hope to enhance the accessibility of this novel immunotherapy to benefit a wider group of cancer patients. We are grateful for all the contributions made by every investigator and patient in this study. We are thrilled to share this news with the medical community and look forward to continuing our efforts to bring this innovative treatment option to market and improve outcomes for more patients with gastric cancer.  Up until now, sintilimab has demonstrated improved survival in 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. Thanks to that, sintilimab has become the only PD-1 inhibitor for the first-line treatment of five high-incidence cancer types in the NRDL."

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 and included in the National Reimbursement Drug List (NRDL) for all 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.

Innovent currently has the regulatory submission for sintilimab in combination with bevacizumab biosimilar and chemotherapy for EGFR-TKI failed EGFR-mutated non-squamous NSCLC under review in the China's NMPA.

Additionally, 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.

About Innovent

Inspired by the spirit of "Start with Integrity, Succeed through Action," Innovent's mission is to develop, manufacture and commercialize high-quality biopharmaceutical products that are affordable to ordinary people. Established in 2011, Innovent is committed to developing, manufacturing and commercializing high-quality innovative medicines for the treatment of cancer, autoimmune disease, metabolic disorder and other major diseases. On October 31, 2018, Innovent was listed on the Main Board of the Stock Exchange of Hong Kong Limited with the stock code: 01801.HK.

Since its inception, Innovent has developed a fully integrated multi-functional platform which includes R&D, CMC (Chemistry, Manufacturing, and Controls), clinical development and commercialization capabilities. Leveraging the platform, the company has built a robust pipeline of 35 valuable assets in the fields of cancer, metabolic disorder, autoimmune disease and other major therapeutic areas, with 8 approved products on the market. These include: TYVYT® (sintilimab injection), BYVASDA® (bevacizumab biosimilar injection), SULINNO® (adalimumab biosimilar injection), HALPRYZA® (rituximab biosimilar injection) , Pemazyre® (pemigatinib oral inhibitor), olverembatinib (BCR-ABL TKI) , Cyramza® (ramucirumab) and Retsevmo® (selpercatinib). An additional 3 assets are under NMPA NDA review, 5 assets are in Phase 3 or pivotal clinical trials, and 19 more molecules are in clinical studies.

Innovent has built an international team with advanced talent in high-end biological drug development and commercialization, including many global experts. The company has also entered into strategic collaborations with Eli Lilly and Company, Sanofi, Adimab, Incyte, MD Anderson Cancer Center and other international partners. Innovent strives to work with many collaborators to help advance China's biopharmaceutical industry, improve drug availability and enhance the quality of the patients' lives. For more information, please visit: www.innoventbio.com. and www.linkedin.com/company/innovent-biologics/.

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.

[i] Sung H, Ferlay J, Siegel RL, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021; 71(3): 209-249.

[ii] Fuchs CS, Shitara K, Di Bartolomeo M, et al. Ramucirumab with cisplatin and fluoropyrimidine as first-line therapy in patients with metastatic gastric or junctional adenocarcinoma (RAINFALL): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2019; 20(3): 420-435.

[iii] Wang H, Guo W, Hu Y, et al. Superiority of the 8th edition of the TNM staging system for predicting overall survival in gastric cancer: Comparative analysis of the 7th and 8th editions in a monoinstitutional cohort[J]. Molecular and Clinical Oncology, 2018, 9(4): 423-431.

[iv] Price TJ, Shapiro JD, Segelov E, Karapetis CS, Pavlakis N, Van Cutsem E, Shah MA, Kang YK, Tebbutt NC. Management of advanced gastric cancer. Expert Rev Gastroenterol Hepatol. 2012 Apr;6(2):199-208; quiz 209. doi: 10.1586/egh.11.103. PMID: 22375525.

[v] Wang J, Fei K, Jing H, et al. Durable blockade of PD-1 signaling links preclinical efficacy of sintilimab to its clinical benefit. mAbs 2019;11(8): 1443-1451.

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