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

NCT06520683 | Recruiting Phase 3

• 1 other identifier: 2024-FXY-219
• Study Type: interventional
• Target: 180
• Locations: 1 country
• Sites: 1

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.

Conditions

Colorectal Cancer; Microsatellite Instability High

Keywords

Adjuvant therapy; Stage II CRC; dMMR/MSI-H; PD-1 blockade

Outcome Measures

Primary Outcomes (1)

• Disease-free survival (DFS)

  DFS (tumor-specific) is defined as time from randomization to tumor relapse or tumor-related death. DFS will be compared between treatment arms using the stratified log rank test at one-sided level 0.025. If zero DFS events are observed in a certain stratum at an interim analysis and unstratified log-rank is used, all subsequent analyses for DFS will use unstratified log-rank test.

  3 years

Secondary Outcomes (2)

• Overall survival (OS)

  5 years

• Incidence of adverse events

  up to 30 days after last treatment

Study Arms (2)

Tislelizumab Arm

EXPERIMENTAL

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

Drug: Tislelizumab; Drug: Adjuvant chemotherapy

Control Arm

ACTIVE COMPARATOR

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

Drug: Adjuvant chemotherapy

Interventions

Tislelizumab DRUG

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

Also known as: Tislelizumab (Tevimbra)

Tislelizumab Arm

Adjuvant chemotherapy DRUG

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

Control Arm; Tislelizumab Arm

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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%.

Sponsors & Collaborators

• Sun Yat-sen University: lead
• BeiGene: collaborator

Study Sites (1)

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

Guangzhou, Guangdong, 510060, China

RECRUITING

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

tislelizumab; Chemotherapy, Adjuvant

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Combined Modality Therapy; Therapeutics; Drug Therapy

Study Officials

• Pei-Rong Ding, M.D.

  Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Bin-Yi Xiao, M.D.

CONTACT

+8615800004780; xiaoby@sysucc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of the Department of Colorectal Surgery

Study Record Dates

• First Submitted: July 20, 2024
• First Posted: July 25, 2024
• Study Start: November 1, 2024
• Primary Completion (Estimated): November 1, 2027
• Study Completion (Estimated): November 1, 2030
• Last Updated: November 7, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)