Sintilimab Plus Chemotherapy Demonstrates Significant Long-Term Survival Benefit in First-Line Non-Squamous NSCLC, with MHC-II Expression as a Predictive Biomarker

SAN FRANCISCO and SUZHOU, China, August 6, 2021 /PRNewswire/ -- Innovent Bio (Hong Kong Stock Exchange stock code: 01801), a biopharmaceutical company dedicated to the research, development, manufacturing, and commercialization of innovative medicines for the treatment of major diseases such as cancer, metabolic diseases, and autoimmune diseases, and Eli Lilly (NYSE: LLY) jointly announced that the latest data from the ORIENT-11 study have been published in the internationally renowned lung cancer journal 《Journal of Thoracic Oncology》 (hereinafter referred to as JTO). The article includes updated survival data and biomarker results from the study, demonstrating that Tyvyt^®(Sintilimab Injection) in combination with pemetrexed and platinum-based chemotherapy significantly prolongs overall survival in patients with first-line non-squamous non-small cell lung cancer compared with chemotherapy alone. The new data provide important insights for sintilimab combination therapy in patients with high expression of major histocompatibility complex (MHC)-II..(The paper link is as followshttps://www.sciencedirect.com/science/article/pii/S1556086421023303）

In August 2020, the interim analysis results of the ORIENT-11 study were presented as an oral presentation at the 21st World Conference on Lung Cancer, and the Phase III clinical trial results were published online concurrently in the Journal of Thoracic Oncology (JTO).

ORIENT-11 is a randomized, double-blind, phase III controlled clinical trial comparing sintilimab or placebo in combination with pemetrexed and platinum as first-line treatment for advanced or recurrent non-squamous non-small cell lung cancer without EGFR sensitizing mutations or ALK gene rearrangements. As of January 15, 2021, the median follow-up time in this study was 22.9 months, with the median overall survival in the sintilimab combination group not yet reached, which was significantly longer than the 16.8 months in the placebo combination group (HR, 0.60, 95%CI: 0.45-0.79; p=0.0003).

Transcriptomic sequencing was performed on baseline tissue samples in this study. The analysis revealed that patients with high or moderate immune cell infiltration in the sintilimab combination therapy group had better progression-free survival. Notably, high expression of genes associated with the major histocompatibility complex (MHC) class II pathway was significantly associated with longer progression-free survival (HR=0.32, 95% CI: 0.19-0.54; p<0.0001) or overall survival (HR=0.36, 95% CI: 0.20-0.64; p=0.0005) in patients.

Professor Zhang Li, principal investigator of the study and corresponding author of this paper from Sun Yat-sen University Cancer Center, stated: “Long-term follow-up results from ORIENT-11 indicate that sintilimab in combination with pemetrexed and platinum-based chemotherapy provides significant benefits for patients with non-squamous non-small cell lung cancer. These results suggest that for treatment-naïve patients with locally advanced or metastatic non-squamous non-small cell lung cancer without EGFR or ALK alterations, sintilimab combined with chemotherapy should be considered as a first-line treatment.”

Dr. Xu Wei, Vice President of Translational Medicine at Innovent Bio and co-corresponding author of this paper, stated: “Immunotherapy, represented by PD-1 inhibitors, has transformed the treatment landscape for non-small cell lung cancer. However, the precise patient populations that benefit from the combination of immunotherapy and chemotherapy remain unclear. We explored gene expression profiles within the tumor microenvironment and found that the infiltration of antigen-presenting cells and high expression of MHC class II-related genes are significantly associated with better clinical efficacy. These findings enhance our understanding of the mechanisms underlying chemoimmunotherapy and provide a scientific rationale for selecting appropriate subjects in future trials. The recognition of these results once again by JTO, one of the top-tier journals in the global lung cancer field, serves as a tremendous encouragement to our research team. We will continue our research to explore more uncharted areas in tumor immunotherapy, aiming to provide further insights for clinical oncology practice.”

Dr. Li Wang, Senior Vice President of Eli Lilly China and Head of the Drug Development and Medical Affairs Center, stated：“We are very pleased to see that data from the ORIENT-11 study confirm that sintilimab combined with pemetrexed and platinum-based chemotherapy provides an overall survival benefit for patients with non-squamous non-small cell lung cancer. Meanwhile, investigating the tumor microenvironment has emerged as a novel exploratory approach in cancer therapy in recent years, which will help researchers identify suitable biomarkers as potential targets for cancer treatment. The biomarker findings from the ORIENT-11 study, published in JTO, will further help us elucidate the mechanism of action of immunotherapy combined with chemotherapy, thereby facilitating the identification of patients who are more responsive to this treatment regimen.””

AboutORIENT-11Clinical Research

The ORIENT-11 study is a trial evaluating sintilimab^®(Sintilimab Injection) or placebo in combination with Alimta^®A randomized, double-blind, phase III controlled clinical study on the efficacy and safety of (Pemetrexed Disodium for Injection) and platinum-based agents in the first-line treatment of advanced or recurrent non-squamous non-small cell lung cancer (ClinicalTrials.gov, NCT03607539). The primary endpoint is progression-free survival assessed by an independent imaging review committee according to RECIST v1.1 criteria. Secondary endpoints include overall survival, safety, etc.

A total of 397 subjects were enrolled in this study and randomized in a 2:1 ratio to receive sintilimab, respectively.^®(Sintilimab Injection) 200 mg or placebo in combination with Alimta^®(pemetrexed disodium for injection) and platinum-based therapy, administered once every 3 weeks; after completing 4 cycles of treatment, transition to Tyvyt (sintilimab) therapy.^®(Sintilimab Injection) or Placebo in Combination with Alimta^®(Pemetrexed Disodium for Injection) maintenance phase: treatment continues until disease progression, unacceptable toxicity, or other circumstances requiring treatment discontinuation. Patients in the control arm with disease progression may conditionally cross over to sintilimab.^®(Sintilimab Injection) monotherapy.

About Lung Cancer

Lung cancer is the leading cause of cancer-related death worldwide, with nearly 1.8 million people dying from the disease globally each year. In the United States, lung cancer is the second most common cancer (excluding skin cancer) and the leading cause of cancer death, accounting for nearly 25% of all cancer deaths -- more than the combined mortality from colorectal, breast, and prostate cancers. Non-small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancers, with approximately 70% of NSCLC patients having the non-squamous cell subtype. Fifty percent of NSCLC patients present with advanced or metastatic disease at the time of diagnosis.

AboutSintilimab

Sintilimab, Chinese brand name: Tyvyt^®(Sintilimab Injection) is an innovative PD-1 inhibitor drug of international quality co-developed by Innovent Biologics and Eli Lilly and Company. Sintilimab is a human immunoglobulin G4 (IgG4) monoclonal antibody that specifically binds to the PD-1 molecule on the surface of T cells, thereby blocking the PD-1/programmed death-ligand 1 (PD-L1) pathway responsible for tumor immune tolerance, and reactivating the anti-tumor activity of lymphocytes to treat tumors. Currently, more than twenty clinical studies (including over ten registration clinical trials) are underway to evaluate the anti-tumor efficacy of sintilimab in various solid tumors and hematological malignancies. Innovent Biologics is also conducting global clinical research programs for Sintilimab Injection.

Sintilimab has been approved in China for four indications, including:

In addition, the marketing application for sintilimab monotherapy as a second-line treatment for squamous NSCLC has been accepted for review by the National Medical Products Administration (NMPA) of China.

Two additional clinical trials for sintilimab have met their study endpoints, including:

In May 2021, the application for marketing approval of sintilimab in combination with pemetrexed and platinum for the first-line treatment of non-squamous NSCLC was formally accepted for review by the U.S. FDA.

Sintilimab was successfully included in China's National Reimbursement Drug List in November 2019, becomingThe first in China, and the only one that yearPD-1 inhibitor included in the National Reimbursement Drug List.

About Innovent

“Built on Trust, Driven by Action”, developing high-quality biologics that are affordable to the public is the vision and goal of Innovent Bio. Founded in 2011, Innovent Bio is dedicated to the development, manufacturing, and commercialization of innovative therapeutics for major diseases including oncology, autoimmune disorders, and metabolic diseases. On October 31, 2018, Innovent Biologics was listed on the Main Board of The Stock Exchange of Hong Kong Limited, with the stock code: 01801.

Since its establishment, the company has distinguished itself among numerous biopharmaceutical enterprises through its innovative achievements and internationalized operational model. It has built a product pipeline comprising 25 new drug candidates, covering multiple therapeutic areas including oncology, metabolic diseases, and autoimmune disorders, six of which have been selected for the National "Major New Drug Innovation and Development" Special Program. The company currently has five products (sintilimab injection, trade name: Tyvyt^®, English Trademark: TYVYT^®; bevacizumab biosimilar, brand name: Byvasda^®, English Trademark: BYVASDA^®; adalimumab biosimilar, brand name: Sulixin^®, English trademark: SULINNO^®; Rituximab biosimilar, brand name: Byvax^®, English Trademark: HALPRYZA^®; pemigatinib oral inhibitor, brand name: Pemazyre^®, English Trademark: PEMAZYRE^®) received marketing approval, one marketing application was accepted by the NMPA, the U.S. marketing application for sintilimab was accepted by the FDA, five candidates entered Phase III or pivotal clinical trials, and an additional 14 products have entered clinical trials. Sintilimab was successfully included in the National Reimbursement Drug List in November 2019, becomingThe first nationwide, and the only one that year.PD-1 inhibitors included in the National Reimbursement Drug List.

Innovent Bio has assembled a world-class talent team specializing in the development and commercialization of advanced biopharmaceuticals, comprising numerous overseas-trained experts, and has established strategic partnerships with international collaborators including Eli Lilly, Adimab, Incyte, MD Anderson Cancer Center, and South Korea’s Hanmi. Innovent Bio hopes to work alongside everyone to advance the development of China’s biopharmaceutical industry, thereby enhancing drug accessibility for the public and fulfilling people’s aspirations for health and well-being. For more details, please visit the company website:www.innoventbio.comor the company's LinkedIn accountwww.linkedin.com/company/innovent-biologics/。

About Eli Lilly

Eli Lilly and Company is a global leader in the pharmaceutical industry, dedicated to improving human health through innovation. Founded over a century ago, the company was built upon its founder’s commitment to producing high-quality medicines to meet genuine medical needs. Today, we remain steadfast in this mission, and it continues to guide all our work. Worldwide, our employees strive tirelessly to discover and deliver life-changing medicines to the patients who need them most. Furthermore, we are committed to enhancing public understanding of diseases, advancing disease management, and giving back to society through philanthropy and volunteer initiatives. To learn more about Eli Lilly and Company, please visit:www.lilly.com。

Strategic Partnership between Eli Lilly and Innovent Bio

Eli Lilly and Company and Innovent Bio entered into a biologics development collaboration in March 2015, which remains one of the largest partnerships to date between a Chinese biopharmaceutical company and a multinational pharmaceutical corporation. Under the terms of the collaboration, Eli Lilly and Innovent Bio will jointly develop and commercialize in China products including Tyvyt^®oncology drugs, including (Sintilimab Injection). In October 2015, both parties announced a further expansion of their established drug development collaboration, adding three novel oncology therapeutic antibodies. In August 2019, the collaboration was extended to the diabetes field, with Innovent Bio authorized to develop and commercialize in China a potentially best-in-class novel clinical-stage diabetes drug from Eli Lilly. These three collaborations with Eli Lilly mark the establishment of a comprehensive strategic partnership between a Chinese innovative biopharmaceutical company and a global pharmaceutical giant, encompassing new drug R&D, clinical research, manufacturing quality, and commercial sales. In August 2020, Eli Lilly and Innovent Bio announced an expansion of their strategic collaboration on sintilimab. Innovent Bio will grant Eli Lilly an exclusive license for sintilimab outside China, and Eli Lilly will be responsible for advancing sintilimab in North America, Europe, and other regions.

Forward-Looking Statements

This press release may contain certain forward-looking statements. These statements are subject to significant risks and uncertainties by their nature. The use of words such as "anticipate," "believe," "forecast," "expect," "intend," and similar terms in connection with the Company is intended to identify forward-looking statements. The Company undertakes no obligation to continuously update these forward-looking statements.

These forward-looking statements are based on the current views, assumptions, expectations, estimates, projections, and understanding of future matters held by the Company's management at the time such statements are made. These statements are not guarantees of future developments and are subject to risks, uncertainties, and other factors, some of which are beyond the Company's control and difficult to predict. Therefore, actual results may differ materially from the information contained in the forward-looking statements due to future changes and developments in our business, competitive environment, and political, economic, legal, and social conditions.