The aim of this study is to evaluate the safety and efficacy of neoadjuvant treatment with pembrolizumab before colonic resection in patients with early-stage (I-III) deficient mismatch repair (dMMR) colon cancer (CC).
The trial is designed as an investigator-initiated, multicenter, prospective, single arm phase II study in patients with stage I-III dMMR CC scheduled for intended curative surgery to determine the efficacy of immunotherapy using pembrolizumab in the neoadjuvant setting. Patients will receive one dose of pembrolizumab (dosage of 4mg/kg, maximum of 400mg) following diagnosis. After 3 weeks a re-evaluation (to assess tumor response) will be performed, followed by standard surgery for resection of the tumor. Surgery will therefore be performed within 3 to 5 weeks after the dose of pembrolizumab treatment. Following the surgical resection the patients may receive post-operative chemotherapy in accordance with the clinical decision. The patients will be followed as per the standard Danish guidelines with CT scans at 1 and 3 years after surgery.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
85
One dosage of 4mg/kg (maximum of 400mg)
Zealand University Hospital
Roskilde, Denmark
Pathological complete response (pCR)
Number of patients with pCR evaluated according to the Mandard tumour regression grading system
Time frame: Tumour specimen evaluated within 2 weeks after surgery.
Safety and tolerability of pembrolizumab administered before surgery
Determined by the incidence and severity of treatment related adverse events according to CTCAE version 5.0
Time frame: Up to approximately 9 weeks
Postoperative surgical complications
Number and severity of postoperative surgical complications determined by Clavien-Dindo classification system.
Time frame: Before and up to 4 weeks after surgery
Immunohistochemistry analysis of markers including CD3, CD8, and PD-L1
Assessment of potential predictive biomarker by investigating immunological markers across pre- and post-treatment biopsies and sequential blood samples.
Time frame: Baseline compared to the surgical specimen at 3-5 weeks
Methylated circulating cell-free DNA
Treatment response evaluated by methylated circulating cell-free DNA (cfDNA) specific for CC analysed across sequential blood samples using the TriMeth test
Time frame: Up to approximately 9 weeks
Gene expression by mRNA
To quantify the expression of genes central to the tumour microenvironment and immune evasion of cancer among others
Time frame: Baseline compared to the surgical specimen at 3-5 weeks
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.