Ipilimumab Injection Plus Sintilimab Receives Priority Review in China for MSI-H/dMMR Colon Cancer

The Center for Drug Evaluation (CDE) of China’s National Medical Products Administration (NMPA) has accepted and granted priority review to the new drug application (NDA) for ipilimumab injection (IBI310) in combination with sintilimab (Tyvyt) as neoadjuvant treatment for patients with resectable microsatellite instability–high (MSI-H) or mismatch repair–deficient (dMMR) colon cancer.1

“There is a huge unmet clinical need for neoadjuvant therapy of resectable MSI-H/dMMR colon cancer in China,” Hui Zhou, PhD, senior vice president of Innovent, the drug’s developer, stated in a news release. “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.”

Both the NDA acceptance and priority review designation are based on findings from the ongoing phase 1b/3 NeoShot trial (NCT05890742), which evaluated the safety and efficacy of ipilimumab in combination with sintilimab as neoadjuvant therapy compared with direct radical surgery in MSI-H/dMMR colon cancer.

Interim analysis by an Independent Data Monitoring Committee confirmed that the study met its primary end point of pathological complete response (pCR) rate. Innovent plans to present more detailed results from the NeoShot trial at future academic conferences or publish these data in academic journals.

“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 [phase 2/3] FOxTROT study [NCT00647530] suggested that neoadjuvant chemotherapy is not effective in MSI-H/dMMR colon cancer, and the pCR rate is only [approximately] 5%,” Rui-Hua Xu, MD, PhD, professor of medical oncology and president of Sun Yat-sen University Cancer Center and principal investigator of the NeoShot study, added. “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.”

NeoShot: Overview and Early-Phase Data

The randomized, controlled, multicenter, pivotal trial will enroll 360 patients at least 18 years of age with previously untreated, histologically confirmed, stage IIb to III primary colon adenocarcinoma.1,2 Patients must also be eligible for radical excision prior to neoadjuvant therapy, have MSI-H or dMMR disease, have 1 or more evaluable lesions per RECIST 1.1 criteria, and an ECOG performance status of 0 or 1.2

In the phase 3 portion of the study, patients will be assigned in a 1:1 fashion to receive either 1 mg/kg of neoadjuvant IBI310 plus 200 mg of sintilimab in cycle 1 and 200 mg of sintilimab in cycle 2, followed by surgery; or radical surgery without neoadjuvant therapy.

The study’s primary end points are pCR rate in the experimental group and event-free survival. Secondary end points include R0 resection rate and overall survival.

Results from the phase 1b portion of this trial, which were previously reported at the 2024 ASCO Annual Meeting, further support the development of this combination.1,3 As of the data cutoff date of February 24, 2024, 101 patients were randomized to receive ipilimumab injection plus sintilimab (n = 52) or sintilimab alone (n = 49).3 In the per-protocol population, the pCR rate was significantly higher in the combination arm (n = 50) than in the sintilimab monotherapy arm (n = 44), at 80.0% (95% CI, 66.28%-89.97%) vs 47.7% (95% CI, 32.46%-63.31%), respectively (P = .0007).

All patients underwent R0 resection.1,3 At a median follow-up of 5.65 months, no disease recurrence was reported. Nodal involvement at postoperative pathological evaluation was observed in 3.9% of patients in the combination arm vs 15.9% in the sintilimab monotherapy arm. Most patients were able to be spared adjuvant therapy per clinical guidelines. Importantly, the addition of ipilimumab to sintilimab did not increase safety risks or delay surgery.

Based on these results, the ipilimumab biosimilar was granted breakthrough therapy designation by the CDE.1

“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,” Xu concluded. “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.”

References

1. NMPA accepts NDA and grants priority review designation to Innovent’s ipilimumab injection, China’s first domestic CTLA-4 inhibitor, in combination with sintilimab as neoadjuvant treatment for colon cancer. News release. Innovent. February 24, 2025. Accessed February 27, 2025. https://www.innoventbio.com/InvestorsAndMedia/PressReleaseDetail?key=509
2. A clinical trial evaluating the efficacy and safety of IBI310 in combination with sintilimab, for neoadjuvant treatment of MSI-H/​dMMR resectable colon cancer. ClinicalTrial.gov. Updated March 15, 2024. Accessed February 27, 2025. https://clinicaltrials.gov/study/NCT05890742?term=NCT05890742&rank=1
3. Xu RH, Wang F, Chen G, et al. Neoadjuvant treatment of IBI310 (anti-CTLA-4 antibody) plus sintilimab (anti-PD-1 antibody) in patients with microsatellite instability-high/mismatch repair-deficient colorectal cancer: results from a randomized, open-labeled, phase Ib study.. J Clin Oncol. 2024;42(suppl 16):3505. doi:10.1200/JCO.2024.42.16_suppl.3505