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

NCT ID: NCT06520683

Last Updated: 2024-11-07

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 180 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-11-01
• Study Completion Date: 2030-11-01

Brief 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.

Conditions

Colorectal Cancer; Microsatellite Instability High

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Tislelizumab Arm

Two cycles of Tislelizumab 200mg intravenously, on day 1 and day 22, with or without adjuvant chemotherapy

Group Type: EXPERIMENTAL

Tislelizumab

Intervention Type: DRUG

\- Tislelizumab 200mg (day 1 and day 22), administered after surgery

Adjuvant chemotherapy

Intervention Type: DRUG

• Adjuvant therapy is not mandatory.
• Optional adjuvant regimens include FOLFOX, CapeOX, 5-FU+LV, or Capecitabine.

Control Arm

Receiving standard of Care (either with adjuvant chemotherapy or surveillance alone).

Group Type: ACTIVE_COMPARATOR

Adjuvant chemotherapy

Intervention Type: DRUG

• Adjuvant therapy is not mandatory.
• Optional adjuvant regimens include FOLFOX, CapeOX, 5-FU+LV, or Capecitabine.

Interventions

Tislelizumab

\- Tislelizumab 200mg (day 1 and day 22), administered after surgery

Intervention Type: DRUG

Adjuvant chemotherapy

• Adjuvant therapy is not mandatory.
• Optional adjuvant regimens include FOLFOX, CapeOX, 5-FU+LV, or Capecitabine.

Intervention Type: DRUG

Other Intervention Names

Tislelizumab (Tevimbra)

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%.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

BeiGene

INDUSTRY

Sponsor Role: collaborator

Sun Yat-sen University

OTHER

Sponsor Role: lead

Responsible Party

Pei-Rong Ding

Director of the Department of Colorectal Surgery

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Pei-Rong Ding, M.D.

Role: PRINCIPAL_INVESTIGATOR

Sun Yat-sen University

Locations

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

Guangzhou, Guangdong, China

Site Status: RECRUITING

Countries

China

Central Contacts

Bin-Yi Xiao, M.D.

Role: CONTACT

xiaoby@sysucc.org.cn

+8615800004780

Facility Contacts

Bin-Yi Xiao, M.D.

Role: primary

xiaoby@sysucc.org.cn

+86-15800004780

Pei-Rong Ding, M.D.

Role: backup

Other Identifiers

2024-FXY-219

Identifier Type: -

Identifier Source: org_study_id