Using PD-1 antibody for treating advanced colorectal cancer

Study of Sintilimab vs Standard Therapy in Participants With Mismatch Repair Deficient (dMMR) or Microsatellite Instability-High (MSI-H) Stage III Colorectal Cancer

This study is testing if a PD-1 antibody can help people with advanced colorectal cancer that has certain genetic features stay cancer-free after surgery, compared to a standard chemotherapy combination.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 323 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Sun Yat-sen University (Academic / other)
• Drugs / interventions: chemotherapy, prednisone
• Locations: 1 site (Guangzhou)
• Trial ID: NCT05236972 on ClinicalTrials.gov

What this trial studies

This phase III interventional study aims to evaluate the effectiveness of a PD-1 antibody in patients with locally advanced stage III colorectal cancer characterized by defective mismatch repair (dMMR) or microsatellite instability-high (MSI-H). Participants will be randomized into two groups: one receiving the PD-1 antibody alone and the other receiving a combination of oxaliplatin and capecitabine. The primary endpoint of the study is to assess disease-free survival among the participants. The study will include patients who have undergone complete surgical resection of their tumors.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with stage III dMMR/MSI-H colorectal cancer who have had their tumors fully surgically resected.

Not a fit: Patients with rectal tumors or those with significant post-operative complications may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could improve disease-free survival rates for patients with advanced colorectal cancer.

How similar studies have performed: Other studies have shown promising results with PD-1 inhibitors in similar patient populations, indicating potential for success in this approach.

Eligibility criteria

Inclusion Criteria:

1. Male or female subjects aged ≥18 years
2. ECOG PS 0/1
3. Histologically proven, stage III (i.e., any T, N1 or N2, M0) adenocarcinoma of the colon (as defined by the presence of the inferior pole of the tumour above the peritoneal reflection - that is, at least 10 cm from the anal margin).
4. Fully surgically resected tumour with clear resection margins (i.e., \>1 mm)
5. Locally confirmed defective mismatch repair (dMMR) tumour (as defined by the lack of staining on either the pre-operative biopsy samples or resection specimens of at least one of the following proteins: MLH1 (mutL homolog 1), MSH2 (mutS homologue 2), MSH6 (mutS homolog 6), PMS2
6. Absence of metastases as shown by post-operative CT scan
7. Absence of major post-operative complications or other clinical conditions that, in the opinion of the investigator, would contraindicate adjuvant chemotherapy

Exclusion Criteria:

1. Rectal tumours (as defined by the presence of the inferior pole of the tumour below the peritoneal reflection - that is, \<15 cm from the anal margin).
2. Inability to start adjuvant chemotherapy within 12 weeks after surgery
3. Administration of neoadjuvant systemic chemotherapy or radiotherapy before surgical resection of colon cancer
4. Prior organ transplantation, including allogeneic stem-cell transplantation
5. Significant acute or chronic infections including, among others:

   known history of testing positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS) positive test for HBV (Hepatitis B) surface antigen or anti-HCV (Hepatitis C) antibody and confirmatory HCV RNA test
6. Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent:
7. Subjects with diabetes type I, vitiligo, psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive treatment are eligible
8. Subjects requiring hormone replacement with corticosteroids are eligible if the steroids are administered only for the purpose of hormonal replacement and at doses ≤10 mg/day of prednisone or equivalent
9. Administration of steroids through a route known to result in a minimal systemic exposure (topical, intranasal, intro-ocular, or inhalation) are acceptable
10. Known severe hypersensitivity reactions to monoclonal antibodies (Grade ≥3 NCI-CTCAE v4.0), any history of anaphylaxis, or uncontrolled asthma (that is, 3 or more features of partially controlled asthma)
11. Persisting toxicity related to prior therapy of Grade \>1 NCI-CTCAE v4.0; however, alopecia and sensory neuropathy Grade ≤2 is acceptable unless oxaliplatin administration is planned as part of the adjuvant treatment
12. Pregnancy or lactation
13. Known alcohol or drug abuse
14. Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (\<6 months prior to enrollment), myocardial infarction (\<6 months prior to enrollment), unstable angina, congestive heart failure (≥ New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication
15. Known history of colitis, pneumonitis and pulmonary fibrosis (for example, inflammatory bowel disease, uncontrolled asthma), which, in the opinion of the 16.Investigator, might impair the subject's tolerance of trial treatment.

Any psychiatric condition that would prohibit the understanding or rendering of informed consent 17.Other invasive malignancy within 2 years except for non-invasive malignancies such as cervical carcinoma in situ, non-melanomatous carcinoma of the skin or ductal carcinoma in situ of the breast that has/have been surgically cured.

Where this trial is running

Guangzhou

• Sun Yat-sen University — Guangzhou, China (Recruiting)

Study contacts

• Study coordinator: Peirong Ding, professor

Conditions Colorectal Carcinoma; dMMR/MSI-H