Innovent Biologics announced that the New Drug Application (NDA) for TABOSUN (ipilimumab N01 injection; R&D Code: IBI310), the first domestic cytotoxic lymphocyte-associated antigen-4 (CTLA-4) monoclonal antibody (mAb), has been approved by China's National Medical Products Administration (NMPA), in combination with sintilimab as neoadjuvant treatment for stage IIB-III resectable microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) colon cancer.

TABOSUN (ipilimumab N01 injection) is the world's first approved CTLA-4 mAb for neoadjuvant treatment of colon cancer. Short-term neoadjuvant treatment with the ipilimumab N01 and sintilimab combination demonstrated a substantial improvement in pathological complete response, offering the potential to benefit a broader population of patients with MSI-H/dMMR colon cancer.

Resectable MSI-H/dMMR colon cancer urgently requires effective neoadjuvant therapies to improve prognosis.

MSI-H/dMMR colon cancer accounts for around 15 percent of all resectable colon cancer cases. Due to its unique biological characteristics, this class of tumour shows limited sensitivity to chemotherapy and generally responds poorly. In recent years, immune checkpoint inhibitors have demonstrated significant efficacy in advanced MSI-H/dMMR colon cancer, but a gap remains in the neoadjuvant setting.

For locally advanced MSI-H/dMMR colon cancer, the current standard of care is direct surgery followed by adjuvant chemotherapy. Under this regimen, approximately 10 percent to 30 percent of patients experience disease recurrence or metastasis after surgery, while chemotherapy-related toxicities may negatively affect quality of life. Thus, in the neoadjuvant setting, there remains an urgent need for more effective therapies to improve outcomes for patients with locally advanced MSI-H/dMMR colon cancer.

Immune Checkpoint Blockade (ICB) therapy targeting PD-1 and CTLA-4 has transformed cancer treatment. The combination of DABOSUN (ipilimumab N01 injection) and TYVYT (sintilimab injection) as neoadjuvant therapy can significantly improve pathological complete response (pCR) rates and allow the majority of patients to avoid adjuvant chemotherapy.

Previously, results from a randomised, controlled phase 1b trial evaluating ipilimumab N01 plus sintilimab as neoadjuvant treatment for MSI-H/dMMR colon cancer were published in the top-tier journal Cancer Cell.

As of 17 June, 2025, 101 patients were enrolled and randomized to receive ipilimumab N01 plus sintilimab (n=52) or sintilimab alone (n=49).

With median follow-up of 21.4 months, no patient experienced disease recurrence.

Approval is based on results from the randomised, controlled, multicenter, pivotal phase III clinical trial (NeoShot, NCT05890742), which evaluated the safety and efficacy of ipilimumab N01 combined with sintilimab as neoadjuvant therapy compared with direct radical surgery for MSI-H/dMMR colon cancer. The primary endpoints are pCR rate and Event-Free Survival (EFS). Interim analysis by the Independent Data Monitoring Committee (IDMC) confirmed that the NeoShot trial met its primary endpoint.

As of 28 November, 2024, among the first 50 patients in the treatment arm, 41 achieved pathological complete response after neoadjuvant treatment, yielding a pCR rate of 82 percent.

Neoadjuvant treatment with ipilimumab N01 combined with sintilimab did not significantly increase safety risks compared with direct surgery.

Detailed results will be presented at future academic conferences or published in academic journals.

Prof Ruihua Xu, the principal investigator of the NeoShot study, Academician of the Chinese Academy of Engineering, from Sun Yat-sen University Cancer Centre, stated, "Achieving R0 resection remains challenging for certain patients with locally advanced colon cancer, who also face substantial surgical trauma and poor prognosis. Results from the FOxTROT study indicated that neoadjuvant chemotherapy provides limited benefit in MSI-H/dMMR colon cancer, with a pCR rate of only around five percent.

The NeoShot trial is the first randomised, controlled phase III clinical trial to show promising efficacy of dual checkpoint inhibition as neoadjuvant therapy in MSI-H/dMMR colon cancer. Interim analysis suggests that ipilimumab N01 with sintilimab as short-term neoadjuvant treatment can lead to pathological complete response in 82 percent of treated patients.

In addition, NeoShot phase Ib and phase III interim results both show the R0 resection under this regimen could reach 100 percent and spare patients from adjuvant chemotherapy. In NeoShot-1b, the dual-immunotherapy neoadjuvant regimen combining ipilimumab N01 and sintilimab significantly improved the pCR rate, which serves as a surrogate endpoint for long-term prognosis.

Based on the existing data, this regimen shows promising potential to reduce recurrence risk and improve long-term survival outcomes. We look forward to observing continued reductions in recurrence with longer-term follow-up. The approval of this dual-immunotherapy regimen is expected to change clinical practice, fill a critical gap in neoadjuvant treatment of colon cancer and benefit more patients with MSI-H/dMMR colon cancer."

Dr Hui Zhou, Chief R&D Officer (Oncology), Innovent, stated, "There remains a substantial unmet clinical need for neoadjuvant therapies for stage IIB-III resectable MSI-H/dMMR colon cancer in China. Interim analysis has shown that the NeoShot trial met its primary endpoint. Through Innovent's efficient and high-quality clinical development, ipilimumab N01 has become China's first domestically developed innovative CTLA-4 inhibitor approved by the NMPA, offering a new treatment option for patients in China with stage IIB-III resectable MSI-H/dMMR colon cancer."