Innovent Releases the ORIENT-31 Phase 3 Study First Interim Analysis Results of Sintilimab plus BYVASDA (bevacizumab biosimilar injection) and Chemotherapy in Patients with EGFR-mutated Nonsquamous Non-small Cell Lung Cancer who Progressed After EGFR-TKI Therapy at ESMO Virtual Plenary 2021

Rhea-AI Summary

Innovent Biologics announced the first interim analysis results from the Phase 3 ORIENT-31 study, which evaluated the combination of sintilimab and BYVASDA® (bevacizumab biosimilar) with chemotherapy in EGFR-mutated non-squamous non-small cell lung cancer (nsqNSCLC) patients post-EGFR-TKI therapy. Results showed a statistically significant improvement in progression-free survival (PFS) for the combination therapy compared to chemotherapy alone (HR 0.464, p<0.0001), with median PFS of 6.9 vs. 4.3 months. Innovent plans to submit a supplemental New Drug Application (sNDA) to the NMPA in China.

Positive

• Statistically significant improvement in PFS (6.9 months for combination therapy vs. 4.3 months for chemotherapy).
• Strong support for the effectiveness of the sintilimab and BYVASDA® combination in treating EGFR-mutated nsqNSCLC.
• No new unexpected safety signals reported, confirming safety profiles consistent with previous studies.

Negative

• The PFS data comparing Arm B (sintilimab plus chemotherapy) to Arm C (chemotherapy alone) was immature at the time of analysis.
• Limited treatment options for patients due to acquired resistance mechanisms after EGFR-TKI therapy.

SAN FRANCISCO and SUZHOU, China, Nov. 21, 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 oncology, metabolic, autoimmune and other major diseases, today announced first interim analysis results of the randomized, double-blinded, multi-center Phase 3 ORIENT-31 study conducted in China evaluating sintilimab and anti-VEGF antibody combination therapy (i.e., sintilimab plus BYVASDA® [bevacizumab biosimilar injection] combined with chemotherapy [pemetrexed and cisplatin]) in patients with EGFR-mutated non-squamous non-small cell lung-cancer (nsqNSCLC) who progressed after EGFR-TKI therapy in an oral presentation at the ESMO (European Society for Medical Oncology) Virtual Plenary: November 2021 (Abstract #300).

In the first 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), Arm A (sintilimab plus BYVASDA®[bevacizumab biosimilar injection] in combination with chemotherapy group) demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) compared with Arm C (chemotherapy group), with a HR of 0.464 (95%CI: 0.337, 0.639; p<0.0001). The median progression-free survival (PFS) (95%CI) was 6.9 months (6.0, 9.3) in Arm A, and 4.3 months (4.1, 5.4) in Arm C. The prespecified PFS futility analysis that compares Arm A to Arm B (sintilimab and chemotherapy group) did not cross futility stopping boundary (HR=0.726, 95%CI: 0.528, 0.998). A numerical benefit of adding BYVASDA® (bevacizumab biosimilar injection) to sintilimab and chemotherapy combination was observed (based on IRRC assessment). Additionally, the key secondary endpoints of objective response rate (ORR) and duration of response (DOR) were improved in Arm A compared with Arm C, and the results of PFS, ORR and DOR assessed by the investigator were consistent with the results assessed by IRRC. The PFS data of Arm B vs Arm C was immature yet, with a numerical benefit observed as well. The safety profile of this study was consistent with that observed in previously reported studies of sintilimab and BYVASDA® (bevacizumab biosimilar injection), without new unexpected safety signals. Innovent plans to review these results and file the supplemental New Drug Application (sNDA) to the National Medical Products Administration (NMPA) in China in the near future.

The principal investigator of the ORIENT-31, Prof. Shun Lu from the Oncology Department of Shanghai Chest Hospital, stated, "Despite initial clinical response to EGFR-TKI, virtually all advanced EGFR-mutated NSCLC inevitably acquire resistance mechanisms and progress after treatment with an EGFR-TKI. For those patients with EGFR-mutated advanced nsqNSCLC who have progressed following EGFR-TKI treatment, platinum-based chemotherapy is the current standard of care, but with limited benefit. New treatment options are imperative for this unmet medical need. Globally, ORIENT-31 is the first prospective, double-blind Phase 3 study to demonstrate significant PFS benefit of combination therapy of PD-1 and VEGF inhibitors with chemotherapy compared to standard care of therapy in this patient population. The study has shown the clinical value of adding sintilimab plus BYVASDA® (bevacizumab biosimilar injection) to platinum-based chemotherapy. I am honored to have this opportunity to share the results of this study as an oral presentation at this year's ESMO Virtual Plenary. This modified regimen brings forth a new and more effective treatment option and provides clinically meaningful benefits to patients with EGFR-mutated nsqNSCLC following treatment with an EGFR TKI."

Dr. Hui Zhou, Senior Vice President of Innovent, stated, "Lung cancer is one of the most prevalent cancers and remains the leading cause of cancer-related mortality both in China and worldwide. EGFR-mutated NSCLC is the most prevalent molecular subtype in Chinese lung cancer patients, accounting for 40% to 50% of nsqNSCLC. While immunotherapy has greatly changed the treatment paradigm for many malignancies, it has not yet conquered driver genes mutated cancers. Drug resistance is unavoidable for 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. The ORIENT-31 data at this year's ESMO indicates the potential of combination therapy to prolong lives of these patients. We are grateful for all the contributions made by the investigators and patients in the ORIENT-31 study – together we accomplished this meaningful milestone."

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

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 in a 1:1:1 ratio 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 480 patients. By the data cutoff date of the first interim analysis, 444 patients were enrolled.

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 worldwide, 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 two regulatory submissions accepted for review in China for sintilimab monotherapy for the first-line treatment of esophageal squamous cell carcinoma, and for sintilimab in combination with chemotherapy for the first-line treatment of unresectable, locally advanced, recurrent or metastatic gastric or gastroesophageal junction adenocarcinoma.

Additionally, three clinical studies of sintilimab have met their primary endpoints:

• Phase 2 study as second-line treatment of esophageal squamous cell carcinoma
• Phase 3 study as second-line treatment for squamous NSCLC with disease progression following platinum-based chemotherapy
• Phase 3 study in combination with BYVASDA® (bevacizumab biosimilar injection) and chemotherapy (pemetrexed and cisplatin) for EGFR-mutated nonsquamous NSCLC following EGFR-TKI treatment.

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 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, and advanced or unresectable hepatocellular carcinoma.

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 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 26 valuable assets in the fields of cancer, metabolic, autoimmune disease and other major therapeutic areas, with 5 products approved for marketing in China – TYVYT® (sintilimab injection), BYVASDA® (bevacizumab biosimilar injection), SULINNO® (adalimumab biosimilar injection), HALPRYZA® (rituximab biosimilar injection) and Pemazyre® (pemigatinib oral inhibitor) , one NDA under NMPA review, a Biologics License Application (BLA) for sintilimab accepted for review 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 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, Adimab, Incyte, MD Anderson Cancer Center, Hanmi 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/.

Note:

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

BYVASDA® (bevacizumab biosimilar injection), SULINNO®, and HALPRYZA® (rituximab 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 is still under clinical study, which 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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FAQ

What are the results of the ORIENT-31 study for IVBIY?

The ORIENT-31 study found that sintilimab plus BYVASDA® with chemotherapy significantly improved progression-free survival (PFS) compared to chemotherapy alone.

When will Innovent file the sNDA for sintilimab and BYVASDA®?

Innovent plans to file the supplemental New Drug Application (sNDA) in the near future after this interim analysis.

What is the significance of the ORIENT-31 study for lung cancer treatment?

The study is notable for demonstrating a significant PFS benefit in patients with EGFR-mutated nsqNSCLC following EGFR-TKI treatment.

What does the data from the ORIENT-31 study mean for patients with EGFR-mutated nsqNSCLC?

The data suggests a new effective treatment option for patients who have limited choices after resistance to EGFR-TKI therapy.

What is the next step for Innovent following the ORIENT-31 study results?

The next step is to review the results and proceed with the sNDA filing to the National Medical Products Administration (NMPA) in China.