Adjuvant PD-1 Blockade for High-risk Stage-II DMMR/MSI-H Colorectal Cancer

This open-label phase III trial investigates the efficacy of two cycles of PD-1 blockade (Tislelizumab) as adjuvant therapy to see how it works compared with standard of care (SOC) in treating patients with stage II dMMR/MSI-H colorectal cancer. The rational of giving PD-1 blockade as adjuvant therapy is based on the fact that tumor recurrence is extremely low among patients receiving neoadjuvant immunotherapy, which suggests that PD-1 blockade may likely improve patients' long-term survival. As for the short course (two cycles), we have the following considerations: firstly, the NICHE-2 trial, which adopted a two-cycle regimen, reported no recurrences during follow-up, suggesting that short-course anti-PD-1 therapy may be sufficient to improve the survival of patients with localized dMMR/MSI-H colorectal cancer. Secondly, the potential benefits of PD-1 blockade should be balanced against its toxicities, because patients with stage-II dMMR colorectal cancer generally have a good prognosis. Two cycles of PD-1 blockade have been shown to have a good safety profile, with low incidence of grade 3-4 and immune-related adverse events.

Sex

All

Minimum age

18 Years

Maximum age

80 Years

Inclusion Criteria:

* dMMR and/or MSI-H colorectal carcinoma that undergo surgical resection
* Pathologically confirmed as stage II (T3-4,N0), with at least one of the following risk factors: 1) T4 (including T4a and T4b); 2) Vascular invasion; 3) Perineural invasion; 4) Poor differentiation (including mucinous and signet-ring carcinoma); 5) Obstruction and/or perforation before surgery.
* Perioperative CT/MR/PET-CT find no signs of metastases
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 10 days prior to study start
* Aged 18-80
* No prior medical therapy (chemotherapy, immunotherapy, biologic or targeted therapy) or radiation therapy for the current cancer
* Adequate organ function

Exclusion Criteria:

* Active autoimmune disease that has required systemic treatment in past 2 years
* Positive surgical margin (R1/R2 resection)
* Presence of post-operative complications that may preclude treatment
* Active infection requiring systemic therapy
* Any other malignant disease within the preceding 5 years with the exception of non-melanomatous skin cancer, carcinoma in situ and early stage disease with a recurrence risk \<5%.