PD-1 Antibody Combined With COX Inhibitor in MSI-H/dMMR or High TMB Colorectal Cancer

NCT03638297 | Unknown Phase 2

• 1 other identifier: GIHSYSU13
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 2

Brief Summary

PD-1(programmed death protein 1)antibody has been to approved in patients with MSI-H/dMMR advanced cancer and has achieved significant efficacy. It is reported that the objective response rate of Pembrolizumab and Nivolumab are 40% and 31.1% in MSI-H/dMMR (microsatellite instability-high/deficiency mismatch repair )colorectal cancer. What's more, most of the patients who had response for PD-1 antibody achieved a long duration of disease control. However, not all patients with MSI-H/dMMR was sensitive to PD-1 antibody despite it is a biomarker for PD-1 antibody treatment. There were about 50-60% of patients with MSI-H/dMMR were insensitive and we don't know why. What's more, it's reported that tumor mutation burden (TMB) may be another biomarker of response to PD-1 therapy. COX (cyclooxygenase)inhibitor has been proved to prevent adenomas in colorectal and it is safe for most of the patients. Preclinical models also showed that COX inhibitor could act with PD-1 antibody in mice and control disease progress. So, this study aims to evaluated efficacy and safety of combination of PD-1 antibody and COX inhibitor in patients with MSI-H/dMMR or high tumor mutation burden colorectal cancer.

Conditions

Colorectal Cancer

Keywords

MSI-H; dMMR; PD-1 antibody; COX inhibitor; tumor mutation burden

Outcome Measures

Primary Outcomes (1)

• Response rate

  CR(complete response) + PR (partial response)rate will be assessed according to the RECIST version 1.1 guidelines.

  6 months

Secondary Outcomes (5)

• Progression free survival

  2 years

• Overall survival time

  5 years

• disease control rate

  6 months

• Toxicity assessed using the NCI common toxicity criteria, version 4.0.

  2 years

• duration of response

  2 years

Study Arms (1)

PD-1 antibody + cox inhibitor

EXPERIMENTAL

BAT1306 + aspirin(celebrex when there is contraindication to aspirin) on day 1-21 every three weeks

Drug: PD-1 antibody + cox inhibitor

Interventions

PD-1 antibody + cox inhibitor DRUG

BAT1306 100mg /pembrolizumab 200mg on day 1 + aspirin 200mg oral (celebrex 400mg oral when there is contraindication to aspirin) on day 1-21 every three weeks Contraindication to aspirin : Allergic or intolerance to aspirin; With peptic ulcers; With hemophilia or other bleeding tendencies; Have the gentic disease glucose-6 phosphate dehydrogenase deficiency.

PD-1 antibody + cox inhibitor

Eligibility Criteria

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

You may qualify if:

• Signed informed consent; able to comply with study and/or follow- up procedures;
• Age:18-75 years old;
• Histological or cytological documentation of colorectal cancer;
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;
• There must be documentation by CT scan, MRI, or intraoperative palpation that tumor is unresectable;
• Have had at least one lines of chemotherapy fail or refuse to receive chemotherapy;
• Histologically confirmed metastatic or primary colorectal cancer as dMMR/MSI-H or whole exon sequence confirmed tumor mutation burden higher than 1000;
• 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.

You may not qualify if:

• Previous treatment with other therapy targeting T-cell costimulation or immune checkpoint pathways;
• 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);
• A previous cancer active within the previous 5 years;
• Subjects with known allergy to the study drugs or to any of its excipients;
• Significant cardiovascular disease including unstable angina or myocardial infarction within 6 months before initiating study treatment;
• Heart failure grade III/IV (NYHA-classification);
• Patients with active infection within 1 week before enrollment (infection caused by fever above 38 °C);
• Patients with severe lung disease (interstitial pneumonia, pulmonary fibrosis, severe emphysema);
• Patients with active gastrointestinal bleeding;
• Patients with serious complications (intestinal obstruction, renal insufficiency, hepatic insufficiency, cerebrovascular disorders);
• Psychiatric disease or a history of central nervous system disease that affects clinical treatment;
• 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;
• Breast- feeding or pregnant women;
• Lack of effective contraception;
• The investigator determined that the patient was not eligible for this clinical trial.

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (2)

Gastrointestinal Hospital, Sun Yat-sen University

Guangzhou, Guangdong, 510655, China

RECRUITING

The Sixth Affiliated Hospital of Sun Yat-sen University

Guangzhou, Guangdong, 510655, China

RECRUITING

Related Publications (1)

• Wu Z, Zhang Y, Cheng Y, Li J, Li F, Wang C, Shi L, Qin G, Zhan W, Cai Y, Xie X, Ling J, Hu H, Zhang J, Deng Y. PD-1 blockade plus COX inhibitors in dMMR metastatic colorectal cancer: Clinical, genomic, and immunologic analyses from the PCOX trial. Med. 2024 Aug 9;5(8):998-1015.e6. doi: 10.1016/j.medj.2024.05.002. Epub 2024 May 24.

  PMID: 38795703 DERIVED

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Cyclooxygenase Inhibitors

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)

Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anti-Inflammatory Agents; Therapeutic Uses; Antirheumatic Agents

Study Officials

• Yanhong Deng, M.D.

  Sixth Affiliated Hospital, Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yanhong Deng, M.D.

CONTACT

008613925106525; dengyanh@mail.sysu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: professor

Study Record Dates

• First Submitted: August 17, 2018
• First Posted: August 20, 2018
• Study Start: August 23, 2018
• Primary Completion: August 20, 2022
• Study Completion: August 31, 2025
• Last Updated: October 17, 2023

Record last verified: 2023-10

Locations

CN (2)