Innovent Releases Final Analysis Results of ORIENT-15: the Phase 3 Study of Sintilimab plus Chemotherapy for the First-Line Treatment of Esophageal Squamous Cell Carcinoma at the AACR Annual Meeting 2023

Rhea-AI Summary

Innovent Biologics announced the final analysis results of the Phase 3 ORIENT-15 study, which evaluated sintilimab combined with chemotherapy for treating esophageal squamous cell carcinoma (ESCC). The study involved 690 patients with a median follow-up of 32.2 months. Sintilimab showed a significant improvement in median overall survival (mOS), reducing the risk of death by 33.9% in all patients (HR 0.661; P<0.0001) and 36.5% in PD-L1 positive patients (HR 0.635; P=0.0001). The estimated OS rates at 12 and 24 months were 64.0% vs 53.5% and 41.4% vs 22.9%, respectively. Sintilimab has been approved by NMPA as a first-line treatment for advanced ESCC and included in China's National Reimbursement Drug List, broadening patient access. Notably, the safety profile aligns with prior studies, indicating no new safety concerns with the extended follow-up.

Positive

• Sintilimab plus chemotherapy improved median overall survival (mOS) by 4.6 months (17.4 vs 12.8 months) in all patients.
• The therapy achieved a 33.9% reduction in risk of death (HR 0.661; P<0.0001).
• The safety profile remained consistent with prior studies, with no new safety signals.
• Sintilimab is now approved for first-line treatment of advanced ESCC by NMPA.
• This treatment has been included in China's National Reimbursement Drug List, increasing patient access.

Negative

• None.

ROCKVILLE, Md. and SUZHOU, China, April 16, 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 that the final analysis results of ORIENT-15, the Phase 3 study evaluating sintilimab in combination with chemotherapy for the first-line treatment of esophageal squamous cell carcinoma (ESCC) were released in a poster presentation at the American Association for Cancer Research (AACR) Annual Meeting 2023 (Abstract CT075).

As of data cutoff date (August 28, 2022), a total of 690 patients were randomly assigned and received treatment, and the median follow-up was 32.2 months.

• Sintilimab plus chemotherapy significantly improved the median overall survival (mOS) over placebo plus chemotherapy with a 33.9% reduction in risk of death (HR 0.661; P<0.0001) and a 4.6-month improvement in mOS (17.4 vs 12.8 months) in all randomized patients (the ITT population); and 36.5% reduction in risk of death (HR 0.635; P=0.0001) and a 3.9-month improvement in mOS (18.4 vs 14.5 months) in PD-L1 positive patients (defined as combined positive score [CPS] ≥10). 
• Estimated OS rates at 12 and 24 months for sintilimab plus chemotherapy versus chemotherapy alone in all randomized patients were 64.0% vs 53.5% and 41.4% vs 22.9%, respectively.
• 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 with approximate 16 months of extended follow-up.

The principal investigator of the ORIENT-15 study, Prof. Shen Lin from Peking University Cancer Hospital and Institute, stated, "More than half of new and fatal cases of esophageal cancer in the world occur in China every year. Esophageal cancer is the fifth most commonly diagnosed cancer and the fourth leading cause of death from cancer in China, and squamous cell carcinoma is the predominant histologic type[i]. The interim analysis of ORIENT-15 met all endpoints, and sintilimab in combination with chemotherapy has been approved by the NMPA to be a first-line treatment option for patients with advanced ESCC. In addition, this new indication of sintilimab has been included in the updated China National Reimbursement Drug List (NRDL), benefiting broader patient groups. In this final analysis, sintilimab in combination with chemotherapy demonstrated continued significant OS benefits, further supporting the use of sintilimab plus chemotherapy as a standard of care for first-line treatment in these patients."

Dr. Hui Zhou, Senior Vice President of Innovent, stated, "The approval of immunotherapy has significantly improved the clinical benefits of standard treatments in patients with advanced esophageal squamous cell carcinoma. According to the results of interim analysis, sintilimab plus chemotherapy has been approved by NMPA. We are also pleased that this indication of sintilimab has been included in the NRDL, making sintilimab the only PD-1 inhibitor for the first-line treatment of five high-incidence cancer types included in the NRDL. In this final analysis, the continued significant OS benefits have been verified in advanced ESCC patients with an acceptable safety profile over time, and further demonstrated that sintilimab as a first-line treatment option will benefit ESCC patients in China."

About the ORIENT-15 Study

ORIENT-15 is a global 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 esophageal squamous cell carcinoma (ClinicalTrials.gov, NCT03748134). At the time of interim analysis, a total of 659 eligible patients (of the planned 676 estimated participants) were enrolled and randomly assigned into the experimental group or control group in a 1:1 ratio. The primary endpoints were overall survival (OS) in all randomized patients and OS in PD-L1 positive (defined as CPS ≥10) patients[ii].

About Esophageal Squamous Cell Carcinoma (ESCC)

Esophageal cancer (EC) is one of the most common malignant tumors worldwide that begins in the inner layer (mucosa) of the esophagus, which connects the throat to the stomach. Based on GLOBOCAN 2020 estimates, approximately 600,000 new cases of esophageal cancer are diagnosed and approximately 540,000 deaths result from the disease worldwide each year^[iii]. Esophageal cancer is the seventh most commonly diagnosed cancer and the sixth leading cause of death from cancer worldwideⁱⁱⁱ. More than half of new and fatal cases of esophageal cancer in the world occur in Chinaⁱ. In China, it is estimated there were approximately 320,000 new cases of esophageal cancer diagnosed and approximately 300,000 deaths resulting from the disease in 2020ⁱ. Esophageal cancer is the fifth most commonly diagnosed cancer and the fourth leading cause of death from cancer in China, where it has a five-year survival rate of only 30%ⁱ.

The two main types of esophageal cancer are squamous cell carcinoma (SCC) and adenocarcinoma. In China, SCC is the predominant histologic type, accounting for more than 90% of all esophageal cancer^[iv]. In the past, first-line standard systemic therapy was chemotherapy based on platinum drugs for unresectable locally advanced, recurrent or metastatic ESCC, which calls for more effective first-line treatment options. Several PD-1 inhibitors have been approved as first-line treatment in combination with chemotherapy^[v]，[vi].

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^[vii]. 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.

 

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[i] Zeng H, Chen W, Zheng R, J, et al. Changing cancer survival in China during 2003-15: a pooled analysis of 17 population-based cancer registries. Lancet Glob Health. 2018;6(5):e555-e567.

[ii] Lu, Z., Wang, J., Shu, Y., Liu, L., Kong, L., Yang, L., ... & Shen, L. (2022). Sintilimab versus placebo in combination with chemotherapy as first line treatment for locally advanced or metastatic oesophageal squamous cell carcinoma (ORIENT-15): multicentre, randomised, double blind, phase 3 trial. bmj, 377.

[iii] Sung H, Ferlay J, Siegel R L, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA: a cancer journal for clinicians, 2021, 71(3): 209-249.

[iv] Arnold M, Ferlay J, van Berge Henegouwen M I, et al. Global burden of oesophageal and gastric cancer by histology and subsite in 2018[J]. Gut, 2020, 69(9): 1564-1571

[v] Guidelines of Chinese society of clinical oncology (CSCO): esophageal cancer 2022.

[vi] National Comprehensive Cancer Network. Esophageal and esophagogastric junction cancers. NCCN Clinical Practice Guidelines in Oncology. Version 2. Published February 11, 2022.

[vii] 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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FAQ

What are the results of the ORIENT-15 Phase 3 study for sintilimab?

The ORIENT-15 study showed that sintilimab combined with chemotherapy significantly improved median overall survival, reducing the risk of death by 33.9% in all patients.

When were the results of the ORIENT-15 study released?

The results were presented at the AACR Annual Meeting on April 16, 2023.

What is sintilimab's approval status in China?

Sintilimab has been approved by NMPA as a first-line treatment option for advanced esophageal squamous cell carcinoma and included in the National Reimbursement Drug List.

What are the implications of sintilimab's inclusion in the National Reimbursement Drug List?

The inclusion of sintilimab in the National Reimbursement Drug List enhances access to treatment for a broader patient population in China.

What were the key endpoints of the ORIENT-15 study?

The primary endpoints were overall survival in all randomized patients and in PD-L1 positive patients.