Innovent Updates the Results from the ORIENT-31 Study of Sintilimab Plus Chemotherapy With or Without Bevacizumab in Patients with EGFR-TKI failed EGFR-mutated Non-Squamous Non-Small Cell Lung Can...

ROCKVILLE, Md. and SUZHOU, China, May 7, 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, metabolic, autoimmune, ophthalmology and other major diseases, announces that second interim analysis and survival analysis results of the ORIENT-31 study (NCT03802240) have been published in the Lancet Respiratory Medicine (https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(23)00135-2/fulltext). This randomized, double-blinded, multi-center Phase 3 study evaluated TYVYT^®(sintilimab) with or without anti-VEGF antibody therapy (BYVASDA^® [bevacizumab injection]) combined with chemotherapy (pemetrexed and cisplatin) in patients with EGFR-mutated non-squamous non-small cell lung-cancer (NSCLC) who progressed after EGFR-TKI therapy. The first interim analysis has been published in the Lancet Oncology in 2022ⁱ.

In the second interim analysis (data cutoff date: March 31^th, 2022), the main purpose is to analyze the median progression-free survival (mPFS) of the preset sintilimab plus chemotherapy group (Arm B) versus chemotherapy group (Arm C) in the intent-to-treat (ITT) population, update the results of sintilimab plus bevacizumab plus chemotherapy group (Arm A) and report the overall survival results of the study for the first time. The median follow-up duration of progression-free survival (PFS) were 12.9 months, 15.1 months, and 14.4 months in Arm A, Arm B and Arm C, respectively. Based on the assessment by the Independent Radiographic Review Committee (IRRC), the median PFS were 7.2 months (95%CI: 6.6, 9.3) in Arm A, 5.5 months (95%CI: 4.5, 6.1) in Arm B, and 4.3 months (95%CI: 4.1, 5.3) in Arm C. Arm B demonstrated a statistically significant and clinically meaningful improvement in PFS compared to Arm C, with a HR of 0.72 (95%CI: 0.55, 0.94, P=0.016), which reached pre-specified superiority boundary value. Significant PFS benefit was sustained in Arm A compared to Arm C with a HR of 0.51 (95%CI: 0.39, 0.67, p<0.0001).

As of data cutoff July 4^th, 2022,  a trend towards overall survival (OS) benefit with Arm A was observed although the median OS for Arm C was prolonged due to crossover after progression in Arm C. The median OS for Arm A and Arm C were 21.1 months vs 19.2 months, HR=0.98. After adjusting for crossover, the OS HR ranged from 0.79 to 0.84. In the exploratory analyses of quality of life, Arm A showed longer median time-to-deterioration of the Global Health Status Dimension Score of EORTC Quality of Life Questionnaire Core 30 (QLQ-C30) compared with Arm C.

The safety results were generally consistent with those in the first interim analysis; in particular, treatment-related adverse events of grade ≥3 were 56% in Arm A, 41% in Arm B and 49% in Arm C. The safety profile of this study was consistent with that observed in previously reported studies of sintilimab and bevacizumab, without new or unexpected safety signals.

Globally, ORIENT-31 is the first multi-center, double-blind, prospective Phase 3 study to demonstrate significant PFS benefit of combination therapy of an anti-PD-1 antibody with chemotherapy in patients with EGFR mutated nsqNSCLC that progressed on prior EGFR-TKI therapy. Sintilimab and chemotherapy group showed significant improved PFS with an optimal safety profile. With the extension of follow-up time, sintilimab plus bevacizumab and chemotherapy group continued to show a durable, clinically meaningful PFS benefit.

The principal investigator of the ORIENT-31 Study, Prof. Shun Lu from the Oncology Department of Shanghai Chest Hospital, stated, " ORIENT-31 is globally the first prospective, randomized, double-blind Phase 3 study that demonstrated significant PFS benefit of combination therapy of anti-PD-1 antibody and chemotherapy with or without bevacizumab in patients with EGFR mutated non-squamous NSCLC that progressed on prior EGFR-TKI therapy, which was revolutionary in immunotherapy. I am pleased to witness the first and second interim analysis results of the ORIENT-31 study were published in international authoritative and influential journals. Besides, I hope that the recent approval of sintilimab in combination with bevacizumab and chemotherapy in treatment of patients with EGFR mutated non-squamous NSCLC that progressed on prior EGFR-TKI therapy can bring a new treatment option benefiting more cancer patients."

Dr. Hui Zhou, Senior Vice President of Innovent, stated, "the ORIENT-31 study is the first Phase 3 study that met primary endpoints in the world evaluating efficacy of PD-1 inhibitor and chemotherapy with or without bevacizumab in patients with EGFR mutated non-squamous NSCLC that progressed on prior EGFR-TKI therapy. The results of first and second interim analysis were published in the Lancet Oncology and the Lancet Respiratory Medicine, respectively. That represents the international academia's recognition of high quality, innovative clinical trial conducted by investigators in China, and is also a milestone marking Innovent's solid and outstanding capabilities in new drug development. Meanwhile, we look forward to the approval of sintilimab in combination with bevacizumab and chemotherapy based on the results of the ORIENT-31 study can bring new hope to patients with EGFR mutated non-squamous NSCLC that progressed on prior EGFR-TKI therapy. Innovent endeavors to advance innovative drug development targeting unmet medical needs, to bring more effective and affordable treatment options to patients in China and the world."

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 bevacizumab, combined with chemotherapy (pemetrexed and cisplatin) in patients with EGFR-mutated locally advanced or metastatic non-squamous NSCLC who have progressed following EGFR TKI treatment (ClinicalTrials.gov, NCT03802240). The primary endpoint is PFS as assessed by IRRC based on RECIST v1.1. The secondary endpoints include overall survival (OS), PFS as assessed by investigators, ORR and safety.

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 cellsⁱⁱ. 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 six indications. The updated NRDL reimbursement scope description 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.

Besides, 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 injection)

BYVASDA^® 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 cellsⁱⁱⁱ. In China, BYVASDA^® is approved and included in NRDL for seven 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 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/.

About Eli Lilly and Company

Lilly is a global healthcare leader that unites caring with discovery to create medicines to make life better for people around the world.

We were founded more than a century ago by a man committed to creating high-quality medicines that meet real needs, and today we remain true to that mission in all our work. Across the globe, Lilly employees work to discover and bring life-changing medicines to those who need them, improve the understanding and management of disease, and give back to communities through philanthropy and volunteerism. To learn more about Lilly, please visit us at www.lilly.com and https://newsroom.lilly.com/social-channels.

About Eli Lilly and Company's strategic cooperation with Innovent Biologics

Lilly entered into a strategic collaboration with Innovent focused on biological medicine in March 2015 – a groundbreaking partnership between a Chinese pharmaceutical company and a multinational pharmaceutical company. Under the agreement, Lilly and Innovent will co-develop and commercialize oncology medicines, including Tyvyt^® (sintilimab injection) in China. In October 2015, the two companies announced the extension of their existing collaboration to include co-development of three additional oncology antibodies targeting oncology indications. In August 2019, Innovent further entered into a licensing agreement with Lilly to develop and commercialize a potentially global best-in-class diabetes medicine in China. Its collaboration with Lilly indicates that Innovent has established a comprehensive level of cooperation between China's innovative pharmaceuticals sector and the international pharmaceuticals sector in fields such as R&D, CMC, clinical development and commercialization. In August 2020, Lilly and Innovent announced a global expansion of their strategic alliance for sintilimab. In March 2022, Lilly and Innovent deepened the strategic partnership in oncology, in which Innovent obtained the sole commercialization rights to import, market, promote, distribute and detail CYRAMZA^® (ramucirumab) and Selpercatinib, and a right of first negotiation for potential future commercialization of pirtobrutinib in Mainland China.

Note:

TYVYT^® (sintilimab injection) is not an approved product in the United States.

BYVASDA^®, SULINNO^®, and HALPRYZA^® are not approved products in the United States.

TYVYT^® (sintilimab injection, Innovent)

BYVASDA^® (bevacizumab injection, Innovent)

HALPRYZA^® (rituximab injection, Innovent)

SULINNO^® (adalimumab 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.

CYRAMZA^® (ramucirumab, Eli Lilly). Cyramza^® was discovered by Eli Lilly and licensed to Innovent for commercialization in Mainland China.

Retsevmo^® (selpercatinib, Eli Lilly). Retsevmo^® was discovered by Eli Lilly and licensed to Innovent for commercialization in Mainland China.

Disclaimer: INNOVENT does not recommend use of any unapproved drugs/indications.

Innovent Biologics, Inc. 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. The Company 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 the Company 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 the Company'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, the Company's competitive environment and political, economic, legal and social conditions.

The Company, the Directors and the employees of the Company 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 materialise or turn out to be incorrect.

References:

ⁱ Lu S, Wu L, Jian H, et al. Sintilimab plus bevacizumab biosimilar IBI305 and chemotherapy for patients with EGFR-mutated non-squamous non-small-cell lung cancer who progressed on EGFR tyrosine-kinase inhibitor therapy (ORIENT-31): first interim results from a randomised, double-blind, multicentre, phase 3 trial. Lancet Oncol. 2022;S1470-2045(22)00382-5. doi:10.1016/S1470-2045(22)00382-5.

ⁱⁱ 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.

ⁱⁱⁱ International Journal of Nanomedicine 2019:14 7643-7663

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