ctDNA-guided Treatment of an Anti-angiogenic TKI Combined With a PD-1 Inhibitor for Advanced pMMR/MSS Colorectal Cancer Failed With Standard Therapy: a Randomized Controlled Phase 2 Clinical Trial
The efficacy of combining TKI with PD-1 inhibitor in the treatment of advanced MSS/pMMR colorectal cancer with low levels of maxVAF in peripheral blood ctDNA failed with standard treatment was assessed, compared to standard treatment as chosen by researchers.
• Age range between 18 and 80 years old.
• ECOG performance status of 0 or 1.
• Histologically confirmed advanced or recurrent colorectal adenocarcinoma.
• Confirmed normal expression of mismatch repair proteins (pMMR) by immunohistochemistry or microsatellite stable (MSS) by PCR/next-generation sequencing.
• Blood ctDNA maxVAF \<6.5% as detected by NGS. blood samples of 8-10ml are to be collected from a qualified testing company for analysis.
• Metastatic colorectal cancer that has failed with previous treatment with fluoropyrimidine (5-fluorouracil or capecitabine), oxaliplatin, irinotecan plus bevacizumab/cetuximab (left-side RAS/BRAF wildtype).
• At least 28 days since the last systemic therapy (oral fluoropyrimidine ≥ 14 days), with the option of receiving palliative radiation therapy to limited areas if completed more than 3 weeks prior.
• At least one measurable lesion according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST V1.1).
• Expected survival of at least 3 months.
⁃ Adequate organ and bone marrow function, with laboratory values within the following limits within 7 days before enrollment:
∙ Complete blood count: Absolute neutrophil count (ANC) ≥1.5×10\^9/L, Platelet count (PLT) ≥100×10\^9/L, Hemoglobin (HGB) ≥9.0 g/dL.
‣ Liver function: Total bilirubin (TBIL) ≤1.5× upper limit of normal (ULN), Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5× ULN, or ≤5× ULN in the presence of liver metastasis.
‣ Kidney function: Serum creatinine (Cr) ≤1.5×ULN, or creatinine clearance ≥50ml/min, Urinalysis showing urine protein \<2+, for patients with baseline urine protein ≥2+, 24-hour urine protein collection should show \<1g.
‣ Coagulation function: International normalized ratio (INR) and activated partial thromboplastin time (APTT) ≤1.5 times ULN.
⁃ Normal electrocardiogram, left ventricular ejection fraction (LVEF) ≥50%.
⁃ No history of other malignancies, except for cured cervical carcinoma in situ, non-melanoma skin cancer, non-invasive bladder tumors, non-invasive lung cancer, or malignant tumors with continuous disease-free survival of ≥5 years following surgical resection.
⁃ Negative pregnancy test for women of childbearing potential, and willingness to use effective contraception during the clinical trial period.
⁃ Voluntary participation in the clinical trial with informed consent provided.