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

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

NCT ID: NCT06520683

Condition: Colorectal Cancer
Microsatellite Instability High

Conditions: Official terms:
Colorectal Neoplasms
Microsatellite Instability
Tislelizumab

Conditions: Keywords:
Adjuvant therapy
Stage II CRC
dMMR/MSI-H
PD-1 blockade

Study type: Interventional

Study phase: Phase 3

Overall status: Recruiting

Study design:

Allocation: Randomized

Intervention model: Parallel Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Drug
Intervention name: Tislelizumab
Description: - Tislelizumab 200mg (day 1 and day 22), administered after surgery
Arm group label: Tislelizumab Arm

Other name: Tislelizumab (Tevimbra)

Intervention type: Drug
Intervention name: Adjuvant chemotherapy
Description: - Adjuvant therapy is not mandatory. - Optional adjuvant regimens include FOLFOX, CapeOX, 5-FU+LV, or Capecitabine.
Arm group label: Control Arm
Arm group label: Tislelizumab Arm

Summary: 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.

Detailed description: This is an open-label, multi-centre, randomised, phase III trial comparing the combination of PD-1 blockade + SOC versus SOC alone as adjuvant therapy for patients with high-risk stage-II dMMR/MSI-H colorectal cancer. Primary Objective: To determine whether the addition of Tislelizumab can significantly improve disease-free survival (DFS) compared to standard of care in patients with high-risk stage-II colorectal cancer. Secondary objectives: - To determine whether the addition of Tislelizumab can significantly improve overall survival (OS) compared to standard of care - To assess the adverse events (AE) profile (including immune-related adverse events, ir-AEs). OUTLINE: Patients are randomized to 1 of 2 arms, stratified by cT4 status. Arm 1 (experimental group): patients receive Tislelizumab 200mg intravenously on day 1, with or without adjuvant chemotherapy, and repeat the treatment on day 22. Patients undergo routine follow-up every 3 months for the first 3 years, and then every 6 months for the year 4-5. Arm 2 (control group): patients receive standard of care (SOC), whether with surveillance alone, single-agent Capecitabine, or CapeOx/FOLFOX, at the discretion of the doctor in charge. Patients undergo routine follow-up every 3 months for the first 3 years, and then every 6 months for the year 4-5. Statistics According to the statistical design, 180 patients (90 per arm) are to be randomized. The study is expected to take up to 36 months to complete accrual.

Criteria for eligibility:
Criteria:
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%.

Gender: All

Minimum age: 18 Years

Maximum age: 80 Years

Healthy volunteers: No

Locations:

Facility:
Name: Dept. of Colorectal Surgery, Sun Yat-sen University Cancer Center. Yuexiu District, Dongfeng East Road 651

Address:
City: Guangzhou
Zip: 510060
Country: China

Status: Recruiting

Contact:
Last name: Bin-Yi Xiao, M.D.

Phone: +86-15800004780
Email: xiaoby@sysucc.org.cn

Contact backup:
Last name: Pei-Rong Ding, M.D.

Start date: November 1, 2024

Completion date: November 1, 2030

Lead sponsor:
Agency: Sun Yat-sen University
Agency class: Other

Collaborator:
Agency: BeiGene
Agency class: Industry

Source: Sun Yat-sen University

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT06520683