On February 22, 2025, 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 in combination with sintilimab as neoadjuvant treatment for resectable microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) colon cancer.
This is China’s first NDA for a domestic CTLA-4 inhibitor and another milestone strengthening sintilimab’s leadership position in cancer immunotherapy. Immune checkpoint blockade (ICB) therapy targeting PD-1 and CTLA-4 has transformed oncology treatment, ipilimumab with sintilimab as a neoadjuvant treatment could increase R0 resection rate, achieve pathological complete response, and relieve the majority of patients from adjuvant chemotherapy burdens. This novel treatment is also expected to reduce recurrence rate and improve long-term prognosis, anticipated to benefit MSI-H/dMMR colon cancer patients upon NDA approval.
The NDA acceptance and Priority Review designation are based on results from a randomized, controlled, multicenter, pivotal Phase 3 clinical trial (NeoShot, NCT05890742) which evaluated the safety and efficacy of ipilimumab combined with sintilimab as neoadjuvant therapy and as compared with 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.
As of February 4, 2024, 101 pts were enrolled (males: 55.4%, median age: 56 years, ECOG PS 1: 54.5%, high risk: 76.2%) and randomized into arm A (n = 52) and arm B (n = 49). In arm A, 1 pt had early termination of treatment (withdrawal). In arm B, 4 pts had early termination of treatment (1 withdrawal, 1 died, 2 continued neoadjuvant sintilimab). Scheduled curative resection were performed in 51 (98.1%) pts in arm A and 45 (91.8%) pts in arm B. Postoperative evaluation revealed mismatch repair-proficient (pMMR) in 1 pt each in arm A and arm B. The pCR rates were 80.0% (40/50, 95%CI: 66.3-90.0) in arm A vs 47.7% (21/44, 95%CI: 32.5-63.3) in arm B (p = 0.0007). All pts received surgery had R0 resection. Median time between first dose of neoadjuvant treatment and surgery was 47 days (range: 35-82). Surgery delay occurred in 3 pts including 2 pts in arm A due to grade 2 hypothyroidism (2 days delay) and grade 1 hyperthyroidism (13 days delay), and 1 pt in arm B for other reason (26 days delay). Treatment-emergent adverse events (TEAEs) occurred in 46 pts (88.5%, grade≥3 in 13 pts) in arm A and 39 pts (79.6%, grade≥3 in 9 pts) in arm B. Immune-related adverse events (irAEs) occurred in 22 pts (42.3%) in arm A and 18 pts (36.7%) in arm B. Grade ≥3 irAEs occurred in 3 pts in arm A, including immune-mediated myocarditis, ileus and enteritis, and in 4 pts in arm B, including alanine aminotransferase increased, rash, hypothyroidism and myocarditis. Serious TRAEs occurred in 4 (7.7%) pts in arm A and 3 (6.1%) pts in arm B. TRAE leading to death occurred in 1 pt in arm B (myocarditis).
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.
At present, there are still many clinical trials of new anti-cancer technologies in China seeking patients. Consultation on new drugs and technologies, you can contact Beijing South Region Oncology Hospital International Department.
Phone Number：4008803716
Email：myimmnet@163.com
References
1.https://www.cde.org.cn/main/xxgk/listpage/9f9c74c73e0f8f56a8bfbc646055026d
Post time: Feb-25-2025