Overview
The purpose of this study is to evaluate the efficacy and safety of fruquintinib and pirfenidone in combination with anti-PD-1 antibody in patients with standard treatment failure of advanced or metastatic pMMR/MSS colorectal adenocarcinoma.
Description
In this study, we explored the potential effectiveness of fruquintinib and pirfenidone in combination with anti-PD-1 antibody, in MSS/pMMR unresectable locally advanced or metastatic colorectal cancer patients who failed standard chemotherapy and testified this new combination in preclinical models. 25 patients were included.
Eligibility
Inclusion Criteria:
- Histologically confirmed diagnosis of unresectable locally advanced, recurrent or metastatic colorectal adenocarcinoma.
- Tumor tissues were identified as mismatch repair-proficient (pMMR) by immunohistochemistry (IHC) method or microsatellite stability (MSS) by polymerase chain reaction (PCR).
- Subjects must have failed at least two lines of prior treatment.
- Subjects must have one measurable lesion according to RECIST v1.1 at least.
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1. 6. 18-75 years old.
7\. Life expectancy of at least 12 weeks. 8. Adequate bone marrow, liver, renal and coagulation function as assessed by the laboratory required by protocol
Exclusion Criteria:
- Previously received anti-programmed death-1 (PD-1) or its ligand (PD-L1) antibody or Pirfenidone.
- Received last dose of anti-tumor therapy (chemotherapy, targeted therapy, tumor immunotherapy or arterial embolization) within 3 weeks of the first dose of study medication.
- Received radiotherapy with 4 weeks of the first dose of study medication.
- Underwent major operation within 4 weeks of the first dose of study medication or open wound, ulcer or fracture.
- Known symptomatic central nervous system (CNS) metastasis and/or carcinomatous meningitis. Subjects received prior treatment and have stable disease more than 4 weeks from first dose of study medication are permitted to enroll.
- Active, known or suspected autoimmune disease or has a history of the disease within the last 2 years.
- Interstitial lung disease requiring corticosteroids.
- Active or poorly controlled serious infections.
- Significant malnutrition.
- Symptomatic congestive heart failure (NYHA Class II-IV) or symptomatic or poorly controlled arrhythmia.
- Uncontrolled hypertension (systolic blood pressure ≥ 150 mmHg or diastolic blood pressure ≥ 100 mmHg) despite standard treatment.
- Within 6 months prior to the enrollment, history of gastrointestinal perforation and/or fistula, gastrointestinal ulcer, bowel obstruction, extensive bowel resection, Crohn\'s disease, or ulcerative colitis, intra-abdominal abscesses, or long-term chronic diarrhea.
- History or evidence of inherited bleeding diathesis or coagulopathy or thrombus
- Any life-threatening bleeding within 3 months prior to the enrollment.
- High risk of bleeding.
