Innovent Releases Interim Analysis Results of Sintilimab plus Chemotherapy for the First-Line Treatment of Esophageal Squamous Cell Carcinoma in the Phase 3 ORIENT-15 Study at ESMO Congress 2021

Rhea-AI Summary

Innovent Biologics announced positive interim results from the Phase 3 ORIENT-15 study, presented at ESMO 2021, validating sintilimab's efficacy when combined with chemotherapy for esophageal squamous cell carcinoma (ESCC). The study achieved all endpoints: a median overall survival (mOS) of 16.7 months versus 12.5 months for the placebo group, and a median progression-free survival (mPFS) of 7.2 months versus 5.7 months. Sintilimab's safety profile was consistent with earlier studies. The company has submitted an application to the NMPA in China to secure first-line treatment approval for ESCC.

Positive

• All endpoints met in Phase 3 ORIENT-15 study.
• Median overall survival (mOS) increased to 16.7 months with sintilimab plus chemotherapy compared to 12.5 months for placebo.
• Median progression-free survival (mPFS) improved to 7.2 months versus 5.7 months for placebo.
• No new safety signals identified; safety profile consistent with previous studies.
• Application submitted to NMPA in China for first-line treatment approval for ESCC.

Negative

• None.

SAN FRANCISCO and SUZHOU, China, Sept. 17, 2021 /PRNewswire/ -- Innovent Biologics, Inc. ("Innovent") (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high quality medicines for the treatment of cancer, metabolic, autoimmune and other major diseases, announced that the interim analysis results of the Phase 3 ORIENT-15 study evaluating sintilimab in combination with chemotherapy for the first-line treatment of esophageal squamous cell carcinoma (ESCC) were released today in an oral presentation at the European Society for Medical Oncology (ESMO) Congress 2021 (Abstract # LBA52).

All endpoints of ORIENT-15 were met at the interim analysis. As of the April 9, 2021 data cutoff, 659 patients were randomly assigned and received treatment. Sintilimab plus chemotherapy (cisplatin plus paclitaxel or cisplatin plus 5-fluorouracil [5-FU]) resulted in a superior median overall survival (mOS) over placebo plus chemotherapy in all randomized patients (the ITT population) (16.7 vs 12.5 months, respectively; HR 0.628; P<0.0001) and in PD-L1 positive patients (defined as combined positive score [CPS] ≥10) (17.2 vs 13.6 months, respectively; HR 0.638; P=0.0018). Sintilimab plus chemotherapy significantly improved median progression-free survival (mPFS) in all randomized patients (7.2 vs 5.7 months, respectively; HR 0.558; P<0.0001) and in PD-L1 positive patients (8.3 vs 6.4 months, respectively; HR 0.580; P<0.0001). 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.

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. The treatment options for locally advanced or metastatic ESCC are limited and represent a significant unmet clinical need. The ORIENT-15 results suggest that sintilimab in combination with chemotherapy may represent a first-line treatment option for patients with advanced or metastatic ESCC."

Dr. Hui Zhou, Senior Vice President of Innovent, stated, "We thank the investigators and study team for their joint effort and, most importantly, we would like to express our sincere gratitude to all the patients who participated in the ORIENT-15 study. We have submitted an application to the National Medical Products Administration (NMPA) of China in early September based on these results, and hope that sintilimab plus chemotherapy can become a first-line treatment option for ESCC patients in the near future ."

About the ORIENT-15 Study

ORIENT-15 is a global randomized, double-blind, multicenter Phase 3 clinical study evaluating sintilimab in combination with chemotherapy (cisplatin plus paclitaxel or cisplatin plus 5-fluorouracil [5-FU]), 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.

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. Esophageal cancer is the seventh most commonly diagnosed cancer and the sixth leading cause of death from cancer worldwide. More than half of new and fatal cases of esophageal cancer in the world occur in China. 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 2020. 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%. In the US, it is estimated there were approximately 18,000 new cases of esophageal cancer diagnosed and approximately 16,000 deaths resulting from the disease in 2020. The five-year survival rate of esophageal cancer is only 20% in the US.

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. In western countries, SCC is approximately 25% of all esophageal cancer. In the past first-line standard systemic therapy was chemotherapy based on platinum drugs for unresectable locally advanced, recurrent or metastatic ESCC. Pembrolizumab has been approved as first-line treatment in combination with chemotherapy.

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.

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, metabolic diseases, and other major therapeutic areas. 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. By leveraging this platform, the company has built a robust pipeline of 26 valuable assets in major therapeutic areas, with 5 products - TYVYT® (sintilimab injection), BYVASDA® (bevacizumab biosimilar injection), SULINNO® (adalimumab biosimilar injection) , HALPRYZA® (rituximab biosimilar injection), and Pemazyre® (pemigatinib oral inhibitor) – officially approved for marketing, 1 asset's NDA under NMPA review, sintilimab's Biologics License Application (BLA) acceptance in the U.S., 5 assets in Phase 3 or pivotal clinical trials, and an additional 15 molecules in clinical studies.

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

Note:

Sintilimab is not an approved product in the United States.

BYVASDA® (bevacizumab biosimilar injection), HALPRYZA® (rituximab biosimilar injection), and SULINNO® (adalimumab 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.

Disclaimer:

1. This indication hasn't been approved in China.
2. Innovent does not recommend any off-label usage.
3. For medical and healthcare professionals only.

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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SOURCE Innovent Biologics, Inc.

FAQ

What were the results of the ORIENT-15 study for sintilimab (IVBIY)?

The ORIENT-15 study showed sintilimab plus chemotherapy improved median overall survival to 16.7 months and median progression-free survival to 7.2 months.

When was the ORIENT-15 interim analysis presented?

The interim analysis results were presented on September 17, 2021, at the ESMO Congress.

What is the significance of the ORIENT-15 study results for esophageal cancer treatment?

The results suggest that sintilimab in combination with chemotherapy may serve as a first-line treatment option for advanced or metastatic esophageal squamous cell carcinoma.

What are the next steps for Innovent after the ORIENT-15 study?

Innovent has submitted an application to the National Medical Products Administration (NMPA) in China to seek first-line treatment approval based on the study results.

How many patients were involved in the ORIENT-15 study?

The study involved 659 patients who were randomly assigned to receive treatment.