China Approves World's First CTLA-4 Antibody for Neoadjuvant Colon Cancer Treatment
核心洞察
Innovent Biologics (搜索)' TABOSUN (搜索) (ipilimumab N01 (搜索)) becomes the world's first approved CTLA-4 (搜索) monoclonal antibody for neoadjuvant treatment of colon cancer (搜索), receiving NMPA approval in combination with sintilimab.
The dual immunotherapy regimen achieved an 82% pathological complete response rate in stage IIB-III resectable MSI-H/dMMR colon cancer (搜索) patients, significantly outperforming standard care.
This approval fills a critical treatment gap for MSI-H/dMMR colon cancer (搜索), which accounts for 15% of resectable cases and shows limited sensitivity to conventional chemotherapy.
China's National Medical Products Administration (NMPA) has approved TABOSUN (搜索) (ipilimumab N01 (搜索) injection) in combination with sintilimab as neoadjuvant treatment for stage IIB-III resectable microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) colon cancer (搜索). This marks the world's first approval of a CTLA-4 (搜索) monoclonal antibody for neoadjuvant treatment of colon cancer, representing a significant breakthrough for patients with this challenging cancer subtype.
Addressing Critical Treatment Gap
MSI-H/dMMR colon cancer (搜索) accounts for approximately 15% of all resectable colon cancer (搜索) cases and presents unique therapeutic challenges. Due to its distinct biological characteristics, this tumor subtype shows limited sensitivity to chemotherapy and generally responds poorly to conventional treatments. Under current standard care involving direct surgery followed by adjuvant chemotherapy, approximately 10%-30% of patients experience disease recurrence or metastasis after surgery, while chemotherapy-related toxicities may negatively affect quality of life.
The approval addresses an urgent unmet medical need in the neoadjuvant setting, where effective therapies have been lacking for locally advanced MSI-H/dMMR colon cancer (搜索) patients.
Exceptional Clinical Performance
The approval is based on results from the randomized, controlled, multicenter, pivotal Phase 3 clinical trial (NeoShot, NCT05890742), which evaluated the safety and efficacy of ipilimumab N01 (搜索) combined with sintilimab as neoadjuvant therapy compared with direct radical surgery. As of November 28, 2024, among the first 50 patients in the treatment arm, 41 achieved pathological complete response after neoadjuvant treatment, yielding a pathological complete response (pCR) rate of 82%.
Earlier Phase 1b trial results published in Cancer Cell demonstrated the combination's superiority over monotherapy. In the per-protocol population of 101 patients, the pCR rate in the ipilimumab N01 (搜索)-plus-sintilimab arm was significantly higher than in the sintilimab-alone arm (80.0% vs 47.7%, p=0.0007). With median follow-up of 21.4 months, no patient experienced disease recurrence.
The dual immunotherapy regimen achieved 100% R0 resection rates and enabled patients to avoid adjuvant chemotherapy, while neoadjuvant treatment with ipilimumab N01 (搜索) combined with sintilimab did not significantly increase safety risks compared with direct surgery.
Clinical Impact and Expert Perspective
Prof. Ruihua Xu from Sun Yat-sen University Cancer Center, the Principal Investigator of the NeoShot study and Academician of the Chinese Academy of Engineering, emphasized the clinical significance: "Results from the FOxTROT study indicated that neoadjuvant chemotherapy provides limited benefit in MSI-H/dMMR colon cancer (搜索), with a pCR rate of 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."
Dr. Hui Zhou, Chief R&D Officer (Oncology) of Innovent, noted: "Through Innovent's efficient and high-quality clinical development, ipilimumab N01 (搜索) has become China's first domestically developed innovative CTLA-4 (搜索) inhibitor approved by the NMPA, offering a new treatment option for patients in China with stage IIB-III resectable MSI-H/dMMR colon cancer (搜索)."
Drug Mechanisms and Development
TABOSUN (搜索) (ipilimumab N01 (搜索)) is a fully human monoclonal antibody that specifically binds cytotoxic T lymphocyte-associated antigen 4 (CTLA-4 (搜索)), blocking CTLA-4-mediated inhibition of T cell activity, promoting T cell activation and proliferation, and improving tumor immune response to achieve anti-tumor effects.
Sintilimab (TYVYT) is a PD-1 (搜索) immunoglobulin G4 monoclonal antibody co-developed by Innovent and Eli Lilly and Company. It binds to PD-1 molecules on T-cell surfaces, blocks the PD-1/PD-Ligand 1 pathway, and reactivates T-cells to kill cancer cells. In China, sintilimab has been approved for eight indications and is included in the National Reimbursement Drug List.