According to results from a phase 1b study, neoadjuvant IBI301 plus sintilimab significantly improved the pathological complete response (pCR) rate compared with sintilimab alone among patients with microsatellite instability-high (MSI-H)/mismatch repair-deficient (dMMR) colorectal cancer. IBI310 is a biosimilar of the anti-CTLA-4 monoclonal antibody ipilimumab.

These data will be presented by Rui-Ha Xu, MD, Sun Yat-sen University Cancer Center, Guangzhou, China, at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois.

In this randomized, open-label phase 1b study, 101 patients with locally advanced, resectable MSI-H/dMMR colorectal cancer were enrolled. Patients were randomized to receive either 1 cycle of IBI310 at 1 mg/kg plus 2 cycles of sintilimab of 200mg 3 times a week (n = 52), or sintilimab alone (n = 49) as neoadjuvant treatment. Curative resection was set to occur between 36 to 56 after the first dose of neoadjuvant treatment. Patients were stratified by risk evaluation at baseline and age. The primary end point was pCR rate with secondary end points including R0 resection rate and safety.

The scheduled curative resection was performed for 51 patients in the IBI310 plus sintilimab arm and 45 patients in the sintilimab alone arm. The pCR rate in the IBI310 plus sintilimab arm was 80.0% vs 47.7% in the sintilimab alone arm (P = .0007). All patients who underwent surgery achieved an R0 resection.

Grade ≥3 treatment-emergent adverse events occurred in 13 patients in the IBI310 plus sintilimab arm and 9 patients in the sintilimab alone arm. Grade ≥3 immune-related adverse events occurred in 3 patients and 4 patients, respectively. Serious treatment-related adverse events occurred in 4 patients and 3 patients respectively. There was 1 treatment-related adverse event which led to death in the sintilimab arm, due to myocarditis.

Source:

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. Presented at the ASCO Annual Meeting. May 31 – June 4, 2024; Chicago, IL. Abstract #3505