Innovent Dosed First Participant in Phase 3 Clinical Study (Neoshot) of IBI310 (Anti-CTLA-4 Monoclonal Antibody) in Combination with Sintilimab for MSI-H/dMMR Colon Cancer Neoadjuvant Therapy

Rhea-AI Summary

Innovent Biologics, Inc. announces the successful dosing of the first participant with IBI310 in a Phase 3 clinical trial for MSI-H/dMMR colon cancer neoadjuvant therapy. The trial aims to evaluate the safety and efficacy of IBI310 combined with sintilimab compared to adjuvant chemotherapy.

ROCKVILLE, Md. and SUZHOU, China, March 26, 2024 /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 the first participant has been successfully dosed with IBI310 (anti-CTLA-4 monoclonal antibody) in combination with sintilimab (PD-1 inhibitor) in a randomized, controlled, multicenter Phase 3 clinical trial (Neoshot), for resectable MSI-H/dMMR^[1] colon cancer (stage cT4 or cN+) neoadjuvant therapy.

Neoshot is the first Phase 3 clinical trial (NCT05890742) in China to investigate MSI-H/dMMR colon cancer neoadjuvant immunotherapy. The study will evaluate the safety and efficacy of IBI310 combined with sintilimab for neoadjuvant therapy, compared with adjuvant chemotherapy after radical surgery for MSI-H/dMMR colon cancer. The primary endpoints are pathologic complete response (pCR) rate and event-free survival (EFS).

Previously, in a randomized, controlled, multicenter Phase 1b study for neoadjuvant therapy in patients with resectable MSI-H/dMMR colon cancer, the pCR rate in the IBI310+sintilimab group was significantly higher as compared with the sintilimab monotherapy group. No subjects in the IBI310+sintilimab group were inoperable due to adverse reactions, and there was no additional safety risk. Data from this Phase 1b trial will be published at an upcoming medical conference or in an academic journal in future.

The Principal Investigator of the Neoshot study, Prof. Ruihua Xu from Sun Yat-sen University Cancer Center, stated, "At present, R0 resection for T4 and/or N+ stage colon cancer patients remain a significant challenge, along with risks of extensive trauma and poor prognosis. The results of the FOxTROT study suggested that neoadjuvant chemotherapy is not effective in MSI-H/dMMR colon cancer, and the pCR rate is only about 5%^[2]. Therefore, effective neoadjuvant treatment scheme is urgently needed to reduce preoperative staging, decrease tumor burden, narrow the scope of radical resection, and increase R0 resection rate, so as to improve long-term prognosis. IBI310 combined with sintilimab is expected to be the first neoadjuvant immunotherapy in China for resectable MSI-H/dMMR colon cancer, which has demonstrated encouraging efficacy and a good tolerance profile in a Phase 1b study. I look forward to working together with other investigators in Neoshot to obtain high-quality clinical data, in support of potentially providing a more effective treatment option for patients with MSI-H/dMMR colon cancer in China."

Dr. Zhou Hui, Senior Vice President of Innovent, stated, "There is a huge unmet clinical need for neoadjuvant therapy of resectable MSI-H/dMMR colon cancer in China. The results of NICHE study showed that postoperative pCR rate after neoadjuvant treatment for locally advanced colon cancer can be well translated into survival benefits^[3]. In the Phase 1b study, IBI310 combined with sintilimab achieved excellent efficacy and safety results. We are pleased that the Phase 3 clinical study of Neoshot has completed the first patient dosing, and we are looking forward to the positive results generating from this study to provide a more ideal treatment option for MSI-H/dMMR colon cancer patients in China."

About Colorectal Cancer

Colorectal cancer is the second most common malignant tumor and the fourth leading cause of cancer death in China. It is estimated that in 2022, there are more than 510,000 new cases and approximately 240,000 fatal cases^[4]. In addition, the incidence of colorectal cancer has continued to rise over the past 15 years^[5]. MSI-H/dMMR is more common in localized colorectal cancer (10-15%) compared to metastatic colorectal cancer (5%)^[6]. T4 and N2 are important prognostic indicators for MSI-H/dMMR colon cancer. Studies have shown that the 3-year disease-free survival rate of MSI-H/dMMR stage III colon cancer patients (T4 and/or N2) is about 60-65%^[7],[8]. Therefore, the perioperative treatment for stage II-III MSI-H/dMMR colon cancer patients needs to be continually improved.

About IBI310

IBI310 is a fully human monoclonal antibody injection independently developed by Innovent. IBI310 can specifically bind cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), thereby blocking CTLA-4 mediated T cell inhibition, promoting T cell activation and proliferation, improving tumor immune response, and achieving anti-tumor effects.

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^[9].

In China, sintilimab has been approved and included in the National Reimbursement Drug List (NRDL) for seven indications. The updated NRDL reimbursement scope of TYVYT^® (sintilimab injection) includes:

• For the treatment of relapsed or refractory classic Hodgkin's lymphoma after two lines or later of systemic 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;
• For the treatment of patients with EGFR-mutated locally advanced or metastatic non-squamous non-small cell lung cancer who progressed after EGFR-TKI therapy;
• For the first-line treatment of unresectable locally advanced or metastatic squamous non-small cell lung cancer;
• For the first-line treatment of unresectable or metastatic hepatocellular carcinoma with no prior systematic treatment;
• For the first-line treatment of unresectable locally advanced, recurrent or metastatic esophageal squamous cell carcinoma;
• For the first-line treatment of unresectable locally advanced, recurrent or metastatic gastric or gastroesophageal junction adenocarcinoma.

In addition, 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.

Disclaimer: The above two indications are still under clinical study, which have not been approved in China. Innovent does not recommend any off-label usage.

About Innovent

Innovent is a leading biopharmaceutical company founded in 2011 with the mission to provide high-quality biologics that are affordable to all. The company discovers, develops, manufactures and commercializes innovative medicines that treat some of the most intractable diseases. Its pioneering therapies treat cancer, cardiovascular and metabolic, autoimmune and eye diseases. Innovent has 10 products in the market, 3 new drug applications under the NMPA review, 5 assets in Phase 3 or pivotal clinical trials and 18 more molecules in early clinical stage. Innovent partners with over 30 global healthcare leaders, including Eli Lilly, Roche, Sanofi, Adimab, Incyte and MD Anderson Cancer Center.

Guided by the motto, "Start with Integrity, Succeed through Action," Innovent maintains the highest standard of industry practices and works collaboratively to advance the biopharmaceutical industry so that first-rate pharmaceutical drugs can become widely accessible. For more information, visit www.innoventbio.com, or follow Innovent on Facebook and LinkedIn.

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.

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.

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.

Reference：

[1] MSI-H/dMMR =microsatellite instability-high or mismatch repair-deficient

[2] Morton D, Seymour M, Magill L, Handley K, Glasbey J, Glimelius B, Palmer A, Seligmann J, Laurberg S, Murakami K, West N, Quirke P, Gray R; FOxTROT Collaborative Group. Preoperative Chemotherapy for Operable Colon Cancer: Mature Results of an International Randomized Controlled Trial. J Clin Oncol. 2023 Mar 10;41(8):1541-1552.

[3] M. Chalabi, et al. Neoadjuvant immune checkpoint inhibition in locally advanced MMR-deficient colon cancer: The NICHE-2 study. LBA7 2022 ESMO Congress

[4]  https://gco.iarc.fr/today/home.

[5] Zheng R, Zeng H, Zhang X. et al. The epidemiology of colorectal cancer in China. Global Health Journal 2018;2(3):8-30.

[6] AndréT, de Gramont A., Vernerey D. et al. Adjuvant Fluorouracil, Leucovorin, and Oxaliplatin in Stage II to III Colon Cancer: Updated 10-Year Survival and Outcomes According to BRAF Mutation and Mismatch Repair Status of the MOSAIC Study. J. Clin. Oncol. 2015;33(35), 4176-4187.

[7] Sinicrope F A, Huebner L J, Laurent-Puig P. et al. Relative contribution of clinical and molecular features to outcome within low and high risk T and N groups in stage III colon cancer (CC). J. Clin. Oncol. 2019;37(15):3520.

[8] Sinicrope F A, Mahoney M R, Smyrk T C. et al. Prognostic Impact of Deficient DNA Mismatch Repair in Patients With Stage III Colon Cancer From a Randomized Trial of FOLFOX-Based Adjuvant Chemotherapy. J. Clin. Oncol. 2013;31(29):3664-3672.

[9] 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.

 

View original content:https://www.prnewswire.com/news-releases/innovent-dosed-first-participant-in-phase-3-clinical-study-neoshot-of-ibi310-anti-ctla-4-monoclonal-antibody-in-combination-with-sintilimab-for-msi-hdmmr-colon-cancer-neoadjuvant-therapy-302099295.html

SOURCE Innovent Biologics

FAQ

What is the significance of the Phase 3 clinical trial announced by Innovent Biologics, Inc.?

The Phase 3 clinical trial aims to investigate the safety and efficacy of IBI310 combined with sintilimab for neoadjuvant therapy in MSI-H/dMMR colon cancer patients.

Who is the Principal Investigator of the Neoshot study mentioned in the press release?

Prof. Ruihua Xu from Sun Yat-sen University Cancer Center is the Principal Investigator of the Neoshot study.

What were the results of the Phase 1b study for neoadjuvant therapy in patients with resectable MSI-H/dMMR colon cancer?

The pCR rate in the IBI310+sintilimab group was significantly higher compared to the sintilimab monotherapy group in the Phase 1b study.

What are the primary endpoints of the Neoshot study?

The primary endpoints of the Neoshot study are pathologic complete response (pCR) rate and event-free survival (EFS).