Combining PD-1 antibody with COX inhibitor for advanced colorectal cancer

PD-1 Antibody Combined With COX Inhibitor in MSI-H/dMMR or High TMB Colorectal Cancer: a Single Arm Phase II Study

This study is testing if a combination of a PD-1 antibody and a COX inhibitor can help people with advanced colorectal cancer that has certain genetic features feel better and improve their treatment results.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 29 (estimated)
• Ages: 18 Years to 80 Years
• Sex: All
• Sponsor: Sun Yat-sen University (other)
• Drugs / interventions: chemotherapy, immunotherapy, Pembrolizumab, Nivolumab
• Locations: 2 sites (Guangzhou, Guangdong and 1 other locations)
• Trial ID: NCT03638297 on ClinicalTrials.gov

What this trial studies

This phase 2 clinical trial investigates the effectiveness of a PD-1 antibody combined with a COX inhibitor in patients with advanced colorectal cancer characterized by microsatellite instability-high (MSI-H) or deficient mismatch repair (dMMR). Eligible participants will receive the treatment every three weeks, and their clinical response will be monitored through imaging techniques such as CT scans. The study aims to explore the potential of this combination therapy to improve outcomes for patients who may not respond adequately to PD-1 antibody treatment alone.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18-75 with unresectable MSI-H/dMMR colorectal cancer who have experienced treatment failure with at least one line of chemotherapy.

Not a fit: Patients with resectable tumors or those who have not undergone prior chemotherapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could enhance response rates and prolong disease control in patients with advanced colorectal cancer.

How similar studies have performed: While the combination of PD-1 antibodies and COX inhibitors is a novel approach, preclinical models have shown promising results, indicating potential for success.

Eligibility criteria

Inclusion Criteria:

1. Signed informed consent; able to comply with study and/or follow- up procedures;
2. Age:18-75 years old;
3. Histological or cytological documentation of colorectal cancer;
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;
5. There must be documentation by CT scan, MRI, or intraoperative palpation that tumor is unresectable;
6. Have had at least one lines of chemotherapy fail or refuse to receive chemotherapy;
7. Histologically confirmed metastatic or primary colorectal cancer as dMMR/MSI-H or whole exon sequence confirmed tumor mutation burden higher than 1000;
8. Adequate bone marrow, hepatic and renal function as assessed by the following laboratory requirements conducted within 7 days of starting study treatment: Hemoglobin (Hb) ≥ 90g/ L, absolute neutrophil count (ANC) ≥ 1.5×109/ L, platelet count ≥ 100×109/ L; Total bilirubin ≤ 1.5×the upper limit of normal (ULN), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 5 ×ULN; Serum creatinine ≤1.5×the ULN.

Exclusion Criteria:

1. Previous treatment with other therapy targeting T-cell costimulation or immune checkpoint pathways;
2. Active, known, or suspected autoimmune disease (except for type 1 diabetes mellitus, residual hypothyroidism due to autoimmune condition requiring only hormone replacement, or conditions not expected to recur in the absence of an external trigger);
3. A previous cancer active within the previous 5 years;
4. Subjects with known allergy to the study drugs or to any of its excipients;
5. Significant cardiovascular disease including unstable angina or myocardial infarction within 6 months before initiating study treatment;
6. Heart failure grade III/IV (NYHA-classification);
7. Patients with active infection within 1 week before enrollment (infection caused by fever above 38 °C);
8. Patients with severe lung disease (interstitial pneumonia, pulmonary fibrosis, severe emphysema);
9. Patients with active gastrointestinal bleeding;
10. Patients with serious complications (intestinal obstruction, renal insufficiency, hepatic insufficiency, cerebrovascular disorders);
11. Psychiatric disease or a history of central nervous system disease that affects clinical treatment;
12. Receive other anti-tumor treatments (including anti-tumor immunotherapy, interventional therapy and intra-serosal injection of anti-tumor drugs) or participate in other interventional clinical trials within two weeks before enrollment;
13. Breast- feeding or pregnant women;
14. Lack of effective contraception;
15. The investigator determined that the patient was not eligible for this clinical trial.

Where this trial is running

Guangzhou, Guangdong and 1 other locations

• Gastrointestinal Hospital, Sun Yat-sen University — Guangzhou, Guangdong, China (RECRUITING)
• The Sixth Affiliated Hospital of Sun Yat-sen University — Guangzhou, Guangdong, China (RECRUITING)

Study contacts

• Principal investigator: Yanhong Deng, M.D. — Sixth Affiliated Hospital, Sun Yat-sen University
• Study coordinator: Yanhong Deng, M.D.

Conditions: Colorectal Cancer, MSI-H, dMMR, PD-1 antibody, COX inhibitor, tumor mutation burden