NMPA Grants Priority Review to Innovent’s Ipilimumab-Sintilimab Combo for Colon Cancer

NMPA Grants Priority Review to Innovent’s Ipilimumab-Sintilimab Combo for Colon Cancer

February 24, 2025 Catherine Williams Health

Innovent Biologics Achieves Milestone with NDA Acceptance for Ipilimumab Injection in China

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— San Francisco and Suzhou, China

San Francisco and Suzhou, China — Innovent Biologics, Inc., a leading biopharmaceutical company, has announced that the New Drug Application (NDA) for ipilimumab injection (anti-CTLA-4 monoclonal antibody; R&D Code: IBI310) has been accepted by the Center for Drug Evaluation (CDE) of China’s National Medical Products Administration (NMPA) and granted Priority Review designation. This approval is for the use of ipilimumab in combination with sintilimab as a neoadjuvant treatment for resectable microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) colon cancer.

This marks a significant milestone not only for Innovent but also for the broader field of cancer immunotherapy. The acceptance of the NDA underscores the growing importance of immune checkpoint blockade (ICB) therapy, which targets PD-1 and CTLA-4. This novel treatment approach is expected to increase the R0 resection rate, achieve pathological complete response, and relieve the majority of patients from the burdens of adjuvant chemotherapy. The potential benefits extend to reducing recurrence rates and improving long-term prognosis for MSI-H/dMMR colon cancer patients.

The NDA acceptance and Priority Review designation are based on results from a randomized, controlled, multicenter, pivotal Phase 3 clinical trial (NeoShot, NCT05890742). This trial evaluated the safety and efficacy of ipilimumab combined with sintilimab as neoadjuvant therapy compared to direct radical surgery for MSI-H/dMMR colon cancer. The primary endpoints are pathologic complete response (pCR) rate and event-free survival (EFS). Interim analysis by the Independent Data Monitoring Committee (IDMC) showed that the NeoShot trial has met its primary endpoint. Detailed results will be presented at future academic conferences or published in academic journals.

Previously, the results of a randomized controlled Phase 1b trial evaluating ipilimumab in combination with sintilimab as neoadjuvant treatment for MSI-H/dMMR colon cancer were presented orally at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting. Based on promising Phase 1b results, the CDE has granted Breakthrough Therapy Designation (BTD) for ipilimumab.

  • As of February 4, 2024, 101 patients were enrolled and randomized to receive ipilimumab plus sintilimab (n=52) or sintilimab alone (n=49).
  • In the per-protocol population, the pCR rate in the ipilimumab-plus-sintilimab arm was significantly higher than in the sintilimab-alone arm (80.0% vs 47.7%, p=0.0007).
  • All patients in both treatment arms had R0 resection. With a median follow-up of 5.65 months, no patient had disease recurrence.
  • At postoperative pathological evaluation, 3.9% of patients with ipilimumab plus sintilimab and 15.9% of patients with sintilimab alone were stage N+. The majority of patients could be relieved from adjuvant treatment according to clinical guidelines.
  • Ipilimumab-plus-sintilimab increased neither safety risk compared to sintilimab alone nor risk for subsequent surgery delay or cancellation.

The Principal Investigator of the NeoShot study, Prof. Ruihua Xu from Sun Yat-sen University Cancer Center, stated: “At present, R0 resection for certain locally advanced colon cancer patients remains 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 around 5%. The NeoShot trial is the first randomized, controlled, Phase 3 clinical trial to show promising efficacy of dual checkpoint inhibition as neoadjuvant therapy in MSI-H/dMMR colon cancer. Results from the phase 1b study suggest that ipilimumab with sintilimab as short-term neoadjuvant treatment could increase R0 resection rate, achieve pathological complete response, and relieve patients from adjuvant chemotherapy burdens. This novel treatment is also expected to lower recurrence rate and improve long-term prognosis. As this dual immunotherapy regimen has the potential to change clinical practice, we look forward to the NDA approval of this novel drug to benefit more MSI-H/dMMR colon cancer patients soon.”

Dr. Hui Zhou, 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. Interim analysis showed that the NeoShot trial has met its primary endpoint. With Innovent’s highly efficient and high-quality clinical development, ipilimumab has become China’s first domestic CTLA-4 inhibitor to submit an NDA. We will actively cooperate with regulatory authorities to accelerate approval, and provide a new treatment option for patients with resectable MSI-H/dMMR colon cancer in China.”

About Ipilimumab

Ipilimumab (R&D code: IBI310) is a fully human monoclonal antibody injection independently developed by Innovent. Ipilimumab 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.

The NDA for ipilimumab in combination with sintilimab as neoadjuvant treatment for resectable microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) colon cancer is under the NMPA review and has been granted Priority Review designation.

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.

In China, sintilimab has been approved and included in the updated NRDL for seven indications. The updated NRDL reimbursement scope for 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.

Furthermore, sintilimab’s eighth indication, in combination with fruquintinib for the treatment of patients with advanced endometrial cancer with pMMR tumors that have failed prior systemic therapy and are not candidates for curative surgery or radiation, was conditionally approved by the NMPA in December 2024. And the NDA for sintilimab in combination with ipilimumab as neoadjuvant treatment for resectable MSI-H/dMMR colon cancer is under the NMPA review and has been granted Priority Review designation.

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 non-small cell lung cancer with disease progression following platinum-based chemotherapy.

About Innovent

Innovent is a leading biopharmaceutical company founded in 2011 with the mission to empower patients worldwide with affordable, high-quality biopharmaceuticals. The company discovers, develops, manufactures, and commercializes innovative medicines that target some of the most intractable diseases. Its pioneering therapies treat cancer, cardiovascular and metabolic, autoimmune, and eye diseases. Innovent has launched 14 products in the market. It has 4 new drug applications under regulatory review, 2 assets in Phase III or pivotal clinical trials and 17 more molecules in early clinical stage. Innovent partners with over 30 global healthcare companies, including Eli Lilly, Sanofi, Incyte, Adimab, LG Chem 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.

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.

References

Q&A: Understanding Innovent Biologics’ NDA Acceptance for Ipilimumab Injection in China

1. What is the significance of Innovent Biologics’ NDA acceptance for Ipilimumab Injection in China?

  • Significance: The acceptance of the New Drug Submission (NDA) for Ipilimumab Injection by China’s National Medical Products Management (NMPA) marks a pivotal moment for Innovent Biologics and the field of cancer immunotherapy. It highlights the increasing relevance of immune checkpoint blockade (ICB) therapy, particularly targeting PD-1 and CTLA-4 pathways.
  • Outcome: The approval is aimed at using Ipilimumab in combination with Sintilimab as a neoadjuvant treatment for resectable microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) colon cancer.This combination is expected to improve R0 resection rates and potentially enhance patient outcomes by reducing recurrence rates and alleviating the necessity for adjuvant chemotherapy.

2. What is the proposed treatment using ipilimumab Injection and sintilimab?

  • Treatment Details: The proposed treatment involves the combination of Ipilimumab Injection (a CTLA-4 monoclonal antibody) and Sintilimab (a PD-1 monoclonal antibody). This combination is designed to act as a neoadjuvant therapy, enhancing the immune system’s ability to target and eliminate cancer cells before surgical intervention.
  • Mechanism: Ipilimumab works by blocking CTLA-4, thereby lifting suppression on T cells, while Sintilimab reactivates T cells to attack cancer cells by inhibiting the PD-1 pathway.

3. What are the promising outcomes from the clinical trials associated with this treatment?

  • Clinical Trial Results: The NeoShot trial, a randomized Phase 3 clinical study, demonstrated meaningful positive outcomes.Interim analysis revealed that the pathologic complete response (pCR) rate in the ipilimumab and Sintilimab combination arm was substantially higher then the Sintilimab alone group (80.0% vs. 47.7%; p=0.0007).
  • Additional Findings: Notably, all patients achieved R0 resection, and no recurrence was observed at a median follow-up of 5.65 months. Moreover, many patients coudl forgo adjuvant treatment based on clinical guidelines.

4. What is the status of Ipilimumab’s approval process in China?

  • Approval Process: As of Febuary 2025, Ipilimumab has gained Priority Review designation by the Center for Drug Evaluation (CDE) of the NMPA, which underscores its potential impact and urgency in providing a new treatment option for MSI-H/dMMR colon cancer patients.
  • Clinical Need: The growing unmet clinical need for effective neoadjuvant therapies in this cancer subset in China has made this approval process highly consequential, as noted by Dr. Hui Zhou, Senior Vice President of Innovent.

5. What are the future prospects for ipilimumab and Sintilimab as treatments?

  • Potential Impact: Experts anticipate that this dual immunotherapy regimen could transform clinical practice by improving surgical outcomes and long-term prognoses for patients with MSI-H/dMMR colon cancer. According to Prof. Ruihua Xu, results suggest that this approach could also lower recurrence rates and offer reprieve from customary adjuvant therapies.
  • Regulatory Milestones: Moving forward, Innovent Biologics plans to actively collaborate with regulatory authorities to expedite the approval process for Ipilimumab and its combination with Sintilimab.

6. Who are the key pharmaceutical companies involved in the progress of these drugs?

  • Development Partners: Sintilimab was co-developed by Innovent and Eli Lilly and Company, while Ipilimumab was independently developed by Innovent. These collaborations reflect the merging of expertise in biotechnology and pharmaceuticals to combat cancer innovatively.

7. What other indications has Sintilimab been approved for in China?

  • Approved Uses: Beyond the combination therapy with Ipilimumab, sintilimab has been approved for various cancer types such as relapsed or refractory classic Hodgkin’s lymphoma, non-small cell lung cancer, and advanced hepatocellular carcinoma, among others. In late 2024, it received conditional approval for a novel combination therapy for endometrial cancer.

8.What can we expect from Innovent Biologics in the future?

  • Company Mission and Pipeline: innovent’s mission is to provide affordable, high-quality biopharmaceuticals worldwide, intending to tackle some of the most significant health challenges with pioneering therapies. With 17 molecules in early clinical stages and two assets in pivotal Phase III trials, the company is strategically poised to continue its impactful contributions to the biopharmaceutical industry.

References

  • Innovent Biologics’ official website provides more updates and detailed details on their drug pipeline and clinical trials: www.innoventbio.com

This Q&A provides a thorough look into the developments surrounding Ipilimumab and Sintilimab, focusing on their clinical importance, approval process, and future potential in treating MSI-H/dMMR colon cancer.