This study will evaluate the safety, and tolerability of Cadonilimab as neoadjuvant treatment for resectable local advanced colorectal cancer patient with dMMR/MSI-H.
Colorectal cancer (CRC) is one of the most common malignant tumours of human beings. Mismatch Repair-deficient (dMMR)/ Microsatellite Instability-high (MSI-H) CRC is a specific subtype of CRC, which accounts for approximately 15% \~20% of all CRC patients,and can not benefit from 5-fluorouracil (5-FU) adjuvant chemotherapy. Once patients have distant metastases, they are not sensitive to traditional palliative chemotherapy, and thus lead to much worse prognosis than that of mismatch repair-proficient (pMMR)/ microsatellite stability (MSS). Neoadjuvant immunotherapy based on mismatch repair (MMR) status in CRC have reported some encouraging data. The NICHE study showed that 20 CRC patients with dMMR achived pathological remission, of which 19 patients with residual tumor ≤10%, 15 patients achived pathological complete remission. Another study (ClinicalTrials.gov, NCT03926338) which investigating the effect of neoadjuvant PD-1 blockade with toripalimab, with or without celecoxib, on mismatch repair-deficient or microsatellite instability-high, locally advanced, colorectal cancer. The result revealed that all 34 patients had an R0 resection. 15 of 17 patients (88%) in the toripalimab plus celecoxib group and 11 of 17 patients (65%) in the toripalimab monotherapy group had a pathological complete response. Cadonilimab (®), a PD-1/CTLA-4 bi-specific antibody, is being developed by Akeso, Inc. for the treatment of a range of solid tumours, including cervical cancer, lung cancer, gastric/gastroesophageal junction cancer, oesophageal squamous cell cancer, liver cancer and nasopharyngeal cancer. Cadonilimab was approved in China in June 2022 for use in patients with relapsed or metastatic cervical cancer (r/mCC) who have progressed on or after platinum-based chemotherapy. Given the reported efficacy data about immunotherapy as neoadjuvant treatment in MSI-H/dMMR CRC, the aim of this study was to investigate the efficacy and safety of Cadonilimab as neoadjuvant treatment for resectable local advanced colorectal cancer patient with the dMMR/MSI-H.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
22
10mg/kg, Q3W for 4 cycles
Henan Cancer Hospital/The affiliated Cancer Hospital of ZhengZhou university
Zhengzhou, Henan, China
Pathological complete response (pCR) rates
Proportion of patients experiencing a pCR to perioperative PD-1/CTLA-4 bi-specific antibody
Time frame: 1 year
Major pathological response rates
The proportion of patients experiencing a major pathological response to perioperative PD-1/CTLA-4 bi-specific antibody
Time frame: 1 year
R0 resection rates
The proportion of patients experiencing a R0 resection after perioperative treatment with PD-1/CTLA-4 bi-specific antibody
Time frame: 1 year
Relapse-free survival (DFS)
Defined as the time from radical surgery to relapse, metastasis or death from any cause
Time frame: 3 years
The incidence of Treatment-related Adverse Events
Assessed by evaluation of treatment-related adverse events
Time frame: 1 year
Number of participants with any treatment-related delays in the planned surgery of no more than 28 days after the last preoperative Cadonilimab dose
Any treatment-related delays in the planned surgery of no more than 28 days after the last preoperative Cadonilimab dose
Time frame: 1 year
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