A Randomized, Uncontrolled, Exploratory Phase 2 Trial of Irinotecan Plus Anlotinib or Further in Combination With Penpulimab as Second-line Treatment of Metastatic Colorectal Cancer (ZL-IRIAN)
This is an exploratory, non-controlled, multi-cohort, phase II small-sample clinical study designed to evaluate the clinical benefit of second-line treatment with anlotinib plus irinotecan or further in combination with a PD-1 monoclonal antibody (penpulimab) in patients with advanced colorectal cancer after first-line treatment failure. To explore the rationality of the combination of chemotherapy and targeted therapy and immunotherapy strategy and obtain relevant survival and safety data. The study will fully evaluate the efficacy, PFS, OS, safety and related biomarkers of the regimen.
• Recurrent/metastatic colorectal adenocarcinoma confirmed by histopathological pathology report;
• The patient received oxaliplatin in combination with fluorouracil as the first-line systemic therapy (with or without anti-EGFR mab or VEGF mab) and failed. Fluorouracil (5-FU, capecitabine, or S-1) and oxaliplatin must be included in the first-line regimens. Treatment failure was defined as: disease progression or intolerable toxicity occurred during treatment or within 3 months after the last treatment; Note: Early adjuvant/neoadjuvant therapy is permitted. If recurrence or metastasis occurs during adjuvant/neoadjuvant therapy or within 6 months after completion, adjuvant/neoadjuvant therapy is considered a failure of first-line chemotherapy for advanced disease;
• With one or more measurable lesions, the longest diameter measured by spiral CT scan should be at least 10 mm, and the longest diameter measured by conventional CT scan should be at least 20 mm (RECIST standard, version 1.1);
• the type of KRAS, NRAS, BRAF, and MSI were known, requiring wild type of BRAF. Cohort A required patients with MSS/pMMR status.
• ECOG score was 0-1;
• Life expectancy ≥12 weeks;
• The patient has recovered from damage caused by other anti-tumor therapy, received cytotoxic drugs, radiotherapy or surgery for ≥4 weeks, and the wound has completely healed;
• Bone marrow capacity and liver and kidney function were sufficiently reserved within 7 days before screening: absolute neutrophil (ANC) count ≥1.5x109 /L; Hemoglobin ≥ 8.0g/ dL; Platelet count ≥80 x109 /L; Total bilirubin \< 1.5 times upper normal limit (ULN); ALT and AST\< 2.5x ULN (with liver metastasis \<5x ULN); Serum creatinine ≤1 x ULN, the clearance rate of endogenous creatinine \>50ml/min;
• Women of childbearing age should take effective contraceptive measures;
⁃ Subjects voluntarily joined the study and signed informed consent with good compliance and follow-up.