Innovent Announces Phase III ORIENT-31 Trial of Tyvyt® (Sintilimab) in Combination with Byvasda® (Bevacizumab Biosimilar) and Chemotherapy Met Primary Endpoint in EGFR-Mutated Nonsquamous NSCLC Patients Previously Treated with EGFR-TKIs

SAN FRANCISCO and SUZHOU, China, Oct. 18, 2021 /PRNewswire/ -- Innovent Biologics Group (HKEX Stock Code: 01801), a biopharmaceutical company dedicated to the research, development, manufacturing and commercialization of innovative drugs for the treatment of major diseases such as cancer, metabolic diseases, and autoimmune diseases, today announced: the innovative PD-1 inhibitor TYVICT® (sintilimab), jointly developed by Innovent Bio and Eli Lilly,^®(Sintilimab Injection) in combination with Byvasda^®A randomized, double-blind, multicenter Phase III clinical study of (Bevacizumab Injection) plus chemotherapy for EGFR-mutant non-squamous non-small cell lung cancer following failure of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) therapy (Study Code: ORIENT-31) met its primary endpoint at the first interim analysis.

This is the first global, prospective, double-blind, multicenter, phase III study to demonstrate that the combination of a PD-1 inhibitor, an anti-angiogenic agent, and chemotherapy significantly improves PFS in patients with EGFR-mutated non-squamous NSCLC following progression on EGFR-TKI therapy.

The first interim analysis conducted by the Independent Data Monitoring Committee (iDMC) showed that, in the intention-to-treat (ITT) population, based on the assessment by the Blinded Independent Radiological Review Committee (BIRRC), Tyvyt^®in combination with BYVASDA®^®and chemotherapy, demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) compared to chemotherapy, meeting the prespecified superiority criteria. Sintilimab (Tyvyt®)^®Data comparing combination chemotherapy versus chemotherapy are not yet mature, showing a trend toward PFS benefit. Additionally, in the prespecified futility analysis, sintilimab^®in combination with Byvasda^®and Chemotherapy Compared with Tyvyt^®Combination chemotherapy did not cross the futility boundary, Tyvyt^®`Adding BYVASDA to combination chemotherapy`^®An improvement in PFS values can be observed. The safety profile is consistent with previously reported clinical trial results for sintilimab and bevacizumab, with no new safety signals identified. Detailed study results will be presented at upcoming international academic conferences.

Prof. Lu Shun, Principal Investigator of the ORIENT-31 study and from the Department of Medical Oncology at Shanghai Chest Hospital, stated: “For patients with EGFR-mutated advanced non-squamous NSCLC who have progressed on EGFR-TKI therapy, platinum-based doublet chemotherapy remains the guideline-recommended standard of care. However, its efficacy is limited, and there is an urgent clinical need for new treatment options. The ORIENT-31 study is the first prospective, double-blind Phase III trial globally to demonstrate that a PD-1 inhibitor-based combination immunotherapy can significantly prolong progression-free survival in this patient population, confirming the clinical value of adding sintilimab and bevacizumab to platinum-based chemotherapy. We look forward to this regimen providing a new and more effective treatment option for lung cancer patients who have progressed following EGFR-TKI therapy.”

Dr. Zhou Hui, Senior Vice President of Innovent Biologics Group, stated: “Lung cancer is the malignancy with the highest incidence and mortality rates both globally and in China. The proportion of EGFR mutations among lung cancer patients in China is as high as 40% to 50%. For patients who have failed treatment with first-, second-, or third-generation EGFR-TKIs, subsequent treatment options remain extremely limited, representing a significant unmet clinical need. Thanks to the unremitting efforts of all investigators, the ORIENT-31 study has yielded highly encouraging results. We sincerely thank every participant who joined this study for partnering with us to complete this landmark clinical trial.”

AboutEGFR-mutant non-squamous NSCLC

Lung cancer is the malignant tumor with the highest mortality rate globally, and its incidence ranks second among all malignancies worldwide. Non-small cell lung cancer (NSCLC) accounts for approximately 80% to 85% of all lung cancer cases, and about 70% of NSCLC patients present with locally advanced or metastatic disease that is unresectable at the time of diagnosis. Among NSCLC patients in China, approximately 70% have non-squamous histology. Within this subgroup, patients with EGFR-mutated non-squamous NSCLC account for roughly 40% to 50%. The recommended standard first-line therapy for these patients is a third-generation EGFR-TKI, or first- or second-generation EGFR-TKIs. However, treatment options and clinical efficacy following disease progression on EGFR-TKIs remain severely limited, highlighting a substantial unmet clinical need.

AboutORIENT-31 Study

The ORIENT-31 study is a trial comparing Tyvyt^®(Sintilimab Injection) with or without Byvasda^®(Bevacizumab Biosimilar) and Chemotherapy for the Efficacy and Safety in Patients with EGFR-Mutated Locally Advanced or Metastatic Non-Squamous Non-Small Cell Lung Cancer Who Have Progressed on EGFR-TKI Therapy: A Randomized, Double-Blind, Multicenter, Phase III Clinical Study (ClinicalTrials.gov, NCT03802240). The primary endpoint is progression-free survival (PFS) assessed by BIRRC according to RECIST v1.1 criteria. Secondary endpoints include overall survival (OS), investigator-assessed PFS according to RECIST v1.1 criteria, objective response rate (ORR), and safety.

Eligible subjects for enrollment include: those with disease progression after first- or second-generation EGFR TKI therapy who are T790M-negative; those who are T790M-positive after progression on first- or second-generation EGFR TKI therapy and subsequently experience disease progression on third-generation EGFR TKI therapy; and those with disease progression after first-line third-generation TKI therapy. Subjects will be randomized in a 1:1:1 ratio to receive either Sintilimab + Bevacizumab + Pemetrexed + Cisplatin, or Sintilimab + Placebo 2 + Pemetrexed + Cisplatin, or Placebo 1 + Placebo 2 + Pemetrexed + Cisplatin. After 4 cycles of combination therapy, subjects will continue maintenance therapy with Sintilimab + Bevacizumab + Pemetrexed, Sintilimab + Placebo 2 + Pemetrexed, or Placebo 1 + Placebo 2 + Pemetrexed, respectively, until disease progression, unacceptable toxicity, or other criteria necessitating treatment discontinuation. A total of 480 subjects are planned to be enrolled.

About Sintilimab

Sintilimab, marketed under the brand name Tyvyt in China^®(Sintilimab Injection) is an innovative PD-1 inhibitor drug of international quality co-developed by Innovent Bio and Eli Lilly. 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 that leads to tumor immune tolerance. This reactivates the anti-tumor activity of lymphocytes, thereby achieving the therapeutic goal of treating tumors. Currently, more than twenty clinical studies (including over 10 registration clinical trials) are ongoing to evaluate the anti-tumor efficacy of sintilimab in various solid tumors and hematological malignancies. Innovent Bio is also conducting global clinical research on Sintilimab Injection.

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

Additionally, the marketing authorization application for sintilimab monotherapy as first-line treatment for esophageal squamous cell carcinoma has been accepted for review by the National Medical Products Administration (NMPA).

Four additional clinical trials of sintilimab have also met their study endpoints, including:

In May 2021, the marketing application for sintilimab in combination with pemetrexed and platinum-based agents 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, becoming the first PD-1 inhibitor in China and the only one that year to be included in the national reimbursement drug list.

About Byvasda^®(Bevacizumab biosimilar)

BYVASDA^®This product is a biosimilar of bevacizumab injection, also known as a recombinant humanized anti-VEGF monoclonal antibody injection. Vascular endothelial growth factor (VEGF) is a critical mediator of angiogenesis and is pathologically overexpressed in the endothelial cells of most human tumors. Anti-VEGF antibodies selectively bind to VEGF with high affinity. By preventing VEGF from binding to its receptors on the surface of vascular endothelial cells, they inhibit the transmission of signaling pathways such as PI3K-Akt/PKB and Ras-Raf-MEK-ERK, thereby suppressing the growth, proliferation, and migration of vascular endothelial cells as well as angiogenesis, reducing vascular permeability, cutting off the blood supply to tumor tissues, inhibiting tumor cell proliferation and metastasis, and inducing tumor cell apoptosis, ultimately achieving anti-tumor therapeutic effects. Since the launch of the reference drug bevacizumab injection, it has been approved globally for the treatment of multiple solid tumors, including non-small cell lung cancer, metastatic colorectal cancer, glioblastoma, renal cell carcinoma, cervical cancer, ovarian cancer, fallopian tube cancer, and primary peritoneal carcinoma. Its significant efficacy and favorable safety profile have been widely recognized. In China, Dayoutong has been approved for indications including the treatment of advanced non-small cell lung cancer, metastatic colorectal cancer, recurrent glioblastoma in adults, and hepatocellular carcinoma.

# About Innovent Biologics

“Committed to Trust, Dedicated to Action”: Developing high-quality biologics that are affordable and accessible to the general public is the vision and goal of Innovent Bio. Founded in 2011, Innovent Bio is dedicated to the research, development, manufacturing, and commercialization of innovative medicines for the treatment of 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 companies through its innovative achievements and international operational model. It has established a product pipeline comprising 26 new drug candidates, covering multiple therapeutic areas including oncology, metabolic diseases, and autoimmune diseases, of which 6 candidates have been selected for the National “Major New Drug Development” Program. The Company currently has 5 products (sintilimab injection, trade name: Tyvyt^®, English Trademark: TYVYT^®; Bevacizumab biosimilar, brand name: Dayoutong^®, English Trademark: BYVASDA^®; Adalimumab biosimilar, brand name: Sulixin^®, English Trademark: SULINNO^®; Rituximab biosimilar, brand name: Byvansa^®, English Trademark: HALPRYZA^®; pemigatinib oral inhibitor, brand name: Dabotan^®, English trademark: PEMAZYRE^®）received marketing approval, one marketing application was accepted by the NMPA, sintilimab’s marketing application in the United States was accepted by the FDA, five drug candidates entered Phase III or pivotal clinical trials, and an additional 15 products have entered clinical trials. Sintilimab was successfully included in the National Reimbursement Drug List in November 2019, becoming the first PD-1 inhibitor in China and the only one included in the list that year.

Innovent Bio has assembled an internationally advanced, high-caliber talent team specializing in the development and commercialization of biopharmaceuticals, including numerous returnee experts, and has established strategic partnerships with international collaborators such as Eli Lilly, Adimab, Incyte, MD Anderson Cancer Center, and Hanmi (South Korea). Innovent Bio hopes to work collaboratively with all stakeholders to elevate 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 company LinkedIn accountwww.linkedin.com/company/innovent-biologics/。

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