Innovent's Sintilimab plus Chemotherapy Demonstrated PFS Benefit in Patients with EGFR-mutated Non-Squamous Non-Small Cell Lung Cancer in the Second Interim Analysis Results of the ORIENT-31 Study

ROCKVILLE, Md. and SUZHOU, China, Sept. 7, 2022 /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, metabolic, autoimmune, ophthalmology and other major diseases, announced second interim analysis results of the randomized, double-blinded, multi-center Phase 3 ORIENT-31 study (NCT03802240) conducted in China evaluating sintilimab with or without anti-VEGF antibody therapy (BYVASDA® [bevacizumab biosimilar injection]) combined with chemotherapy [pemetrexed and cisplatin] in patients with EGFR-mutatednon-squamous non-small cell lung-cancer (nsqNSCLC) who progressed after EGFR-TKI therapy in a mini oral presentation at the European Society for Medical Oncology (ESMO) Congress 2022 (Abstract #LBA58).

In the second interim analysis reviewed by the Independent Data Monitoring Committee (IDMC), in the intent-to-treat (ITT) population, based on assessment by the Independent Radiographic Review Committee (IRRC), the median progression-free survival (PFS) (95%CI) was 7.2 months (6.6, 9.3), 5.5 months (4.5, 6.1), and 4.3 months (4.1, 5.3) in Arm A (sintilimab plus BYVASDA®[bevacizumab biosimilar injection] and chemotherapy group), Arm B (sintilimab and chemotherapy group) and Arm C (chemotherapy group) respectively. In this analysis, the PFS benefit of Arm A versus Arm C was consistent with the first interim analysis. Arm B demonstrated a statistically significant and clinically meaningful improvement in PFS compared with Arm C, with a HR of 0.723（95%CI: 0.552, 0.948 P=0.0181）. Additionally, the key secondary endpoints of objective response rate (ORR) and duration of response (DOR) were both improved in Arm B compared with Arm C. Globally, ORIENT-31 is the first prospective, double-blind Phase 3 study to demonstrate significant PFS benefit of combination therapy of an anti-PD-1 antibody with or without VEGF inhibitors and chemotherapy compared to standard care of therapy in patients with EGFR mutated nsqNSCLC that progressed on prior EGFR-TKI therapy. The safety profile of this study was consistent with that observed in previously reported studies of sintilimab and BYVASDA® (bevacizumab biosimilar injection), without new or unexpected safety signals.

The principal investigator of the ORIENT-31 Study, Prof. Shun Lu from the Oncology Department of Shanghai Chest Hospital, stated, "EGFR-TKI targeted therapy is the first treatment choice in NSCLC patients with EGFR sensitive mutation. However, almost all patients will eventually develop TKI-resistance and progression of disease as there are no good treatment options for EGFR-TKI failed NSCLC population. This has become the main concern of clinical physicians. In recent years, immunotherapy has developed rapidly in driver gene-negative cancers, but it has not yet conquered driver genes mutated cancers. In the ORIENT-31 study, sintilimab plus chemotherapy showed a statistically significant improvement in PFS compared to standard platinum-based chemotherapy in EGFR-TKI failed NSCLC. Immunotherapy combination therapy may be a new treatment option for patients living with NSCLC with EGFR-TKI resistance."

Dr. Hui Zhou, Senior Vice President of Innovent, stated, "Drug resistance is unavoidable for most patients with EGFR-mutated advanced NSCLC after first, second and third generation EGFR-TKIs treatments, with limited treatment options, representing a large unmet medical need. Last year, the first interim analysis results of ORIENT-31 demonstrated significant PFS benefit of combination therapy of PD-1 and VEGF inhibitors with chemotherapy compared to chemotherapy alone in EGFR-TKI failed nsqNSCLC. Additionally, at this year's ESMO Congress, we presented results that further demonstrated that PD-1 combined with chemotherapy could also benefit this population. We hope the two modified regimens can provide clinically meaningful benefits to patients with EGFR-TKI failed EGFR-mutated nsqNSCLC."

About Non-Squamous Non-Small Cell Lung Cancer (nsqNSCLC)

Lung cancer is the leading cause of cancer death worldwide, and the second most commonly diagnosed tumor type. Non-small cell lung cancer (NSCLC) accounts for about 80% to 85% of all lung cancer, in which about 70% of NSCLC patients present with locally advanced or metastatic disease that is not suitable for surgical resection at diagnosis. In China, nsqNSCLC accounts for 70% of NSCLC, in which about 40% to 50% of nsqNSCLC patients have an EGFR mutation. The standard first-line treatment for patients with advanced EGFR-mutated NSCLC is a third generation EGFR TKI, or first or second-generation EGFR TKI. For patients who have progressed following EGFR-TKI treatment, platinum-based chemotherapy is still the standard therapy with limited benefit, representing a large unmet medical need.

About the ORIENT-31 Study

ORIENT-31 is a randomized, double-blind, multi-center Phase 3 clinical study conducted in China evaluating sintilimab, with or without BYVASDA® (bevacizumab biosimilar injection), combined with chemotherapy (pemetrexed and cisplatin) in patients with EGFR-mutated locally advanced or metastatic nsqNSCLC who have progressed following EGFR TKI treatment (ClinicalTrials.gov, NCT003802240). The primary endpoint is PFS as assessed by BIRRC based on RECIST v1.1. The secondary endpoints include overall survival (OS), PFS as assessed by investigators, ORR and safety.

Eligible patients included: patients with disease progression following first- or second-generation EGFR TKI and confirmed as T790M negative, or T790M positive but further progressed on third generation EGFR-TKI treatment, or patients with disease progression following third generation EGFR TKI as first line treatment.

Patients were randomized to receive sintilimab plus BYVASDA® (bevacizumab biosimilar injection) combined with pemetrexed and cisplatin (Arm A), sintilimab plus placebo 2 combined with pemetrexed and cisplatin (Arm B), or placebo 1 plus placebo 2 combined with pemetrexed and cisplatin (Arm C). After 4 cycles of combination treatment, patients will receive maintenance treatment of sintilimab plus BYVASDA® and pemetrexed, sintilimab plus placebo 2 and pemetrexed, placebo 1 plus placebo 2 and pemetrexed, until radiographic disease progression, unacceptable toxicity or any other conditions that required treatment discontinuation. Target accrual is 630 patients. By the data cutoff date of the second interim analysis, 476 patients were enrolled.

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. 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 six indications as below, with the first four included in the National Reimbursement Drug List (NRDL), 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 unresectable locally advanced or metastatic non-squamous non-small cell lung cancer lacking EGFR or ALK driver gene mutations;
• In combination with gemcitabine and platinum chemotherapy, for the first-line treatment of unresectable locally advanced or metastatic squamous non-small cell lung cancer;
• In combination with BYVASDA® (bevacizumab biosimilar injection) for the first-line treatment of unresectable locally advanced or metastatic hepatocellular carcinoma;
• In combination with cisplatin plus paclitaxel or cisplatin plus 5-fluorouracil for the first-line treatment of unresectable locally advanced, recurrent or metastatic esophageal squamous cell carcinoma;
• In combination with fluorouracil and platinum-based chemotherapy for the first-line treatment of unresectable locally advanced, recurrent or metastatic gastric or gastroesophageal junction adenocarcinoma.

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 BYVASDA^® (bevacizumab biosimilar injection)

BYVASDA^®, also known as IBI305, is a bevacizumab biosimilar and a recombinant humanized anti-VEGF monoclonal antibody drug. Vascular endothelial growth factor (VEGF) is an important factor in angiogenesis that is highly expressed by the endothelial cells in most human tumors. An anti-VEGF antibody binds VEGF-A selectively with high affinity and blocks its binding to VEGF-2 receptors on the surface of vascular endothelial cells, thereby inhibiting signaling pathways such as PI3K-Akt/PKB and Ras-Raf-MEK-ERK. BYVASDA^® produces anti-tumor effects by inhibiting the growth, proliferation and migration of vascular endothelial cells, blocking angiogenesis, reducing vascular permeability, blocking blood supply to tumor tissues, inhibiting the proliferation and metastasis of tumor cells and inducing apoptosis in tumor cells. Since its launch, bevacizumab has been approved for the treatment of patients with multiple malignant tumors globally, including non-small cell lung cancer, metastatic colorectal cancer, glioblastoma, renal cell carcinoma, cervical cancer, and epithelial ovarian, fallopian tube, or primary peritoneal cancer. The efficacy and safety of bevacizumab in these tumor types have been well recognized worldwide.

In China, BYVASDA® (bevacizumab biosimilar injection) is approved for indications including advanced non-small cell lung cancer, metastatic colorectal cancer, adult recurrent glioblastoma, advanced or unresectable hepatocellular carcinoma, epithelial ovarian, fallopian tube, or primary peritoneal cancer and cervical cancer.

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, ophthalmology 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 34 valuable assets in the fields of cancer, metabolic, autoimmune, ophthalmology and other major therapeutic areas, with 7 products approved for marketing in China – TYVYT® (sintilimab injection), BYVASDA® (bevacizumab biosimilar injection), SULINNO® (adalimumab biosimilar injection), HALPRYZA® (rituximab biosimilar injection), Pemazyre® (pemigatinib oral inhibitor), NAILIKE (olverembatinib) and Cyramza® (ramucirumab), 3 assets under NMPA NDA review, 4 assets in Phase 3 or pivotal clinical trials, and an additional 20 molecules 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, 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/.

Disclaimer:

1. This indication is still under clinical study, which hasn't been approved in China.

2. Innovent does not recommend any off-label usage.

Forward-Looking Statements

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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.

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