This is a single-arm clinical study aiming to enroll 30 colon cancer patients with liver-only metastases. All eligible participants will undergo screening and enrollment after signing the informed consent form.
All patients will receive stereotactic body radiation therapy (SBRT) targeting 1 to 3 liver lesions (each \< 3 cm) at a total dose of 50 Gy delivered in 5 fractions. For lesions adjacent to the liver capsule, portal vein or bile duct, the target volume can be expanded by 5-10 mm outside the visible lesion boundary. One week after radiotherapy completion, patients will be treated with QL1706 (Apalitamab-Tovorizumab, 5 mg/kg, iv, Q3W) combined with CAPOX plus bevacizumab.
Preoperative treatment consists of up to 6 cycles, with each cycle lasting 3 weeks. Efficacy assessment will be conducted every 2 cycles. The investigator or multidisciplinary team (MDT) will decide to initiate curative treatment (surgical resection or radiofrequency ablation of liver metastases, combined with synchronous or staged resection of primary colon lesion) or continue conversion therapy. Surgery shall be scheduled 6 weeks after the final dose of bevacizumab. During the preoperative waiting period, one extra cycle of QL1706 (5 mg/kg, iv, Q3W) plus CAPOX is permitted. The interval between the last immunochemotherapy administration and surgery is required to be 2-3 weeks.
Adjuvant therapy is scheduled to start 3 weeks after surgery, and must be initiated no later than 2 months postoperatively. The investigator will determine the use of QL1706 and/or bevacizumab in adjuvant setting according to individual patient conditions. If the time from surgery to adjuvant therapy is less than 4 weeks, the first postoperative cycle will use QL1706 (5 mg/kg, iv, Q3W) combined with CAPOX only. Postoperative QL1706 maintenance treatment will not exceed 1 year. Patients receiving postoperative systemic adjuvant chemotherapy will complete 8 cycles of perioperative CAPOX with or without bevacizumab.
Patients with progressive disease (PD) or those who fail conversion therapy within 18 weeks will switch to alternative systemic regimens in accordance with the 2025 guidelines issued by the Chinese Society of Clinical Oncology (CSCO) and the National Comprehensive Cancer Network (NCCN).
CAPOX + bevacizumab regimen (repeated every 3 weeks):
Oxaliplatin: 130 mg/m², intravenous infusion over 2 hours, d1; Capecitabine: 1000 mg/m² per dose, po, bid, d1-14; Bevacizumab: 7.5 mg/kg, ivgtt, d1.
Aged 18 to 70 years, male or female.
Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
Histologically or cytologically confirmed colon adenocarcinoma, with pathologically or radiographically verified liver-only metastases.
Microsatellite stable (MSS) / proficient mismatch repair (pMMR) confirmed by immunohistochemistry (IHC) or polymerase chain reaction (PCR).
Confirmed non-adenocarcinoma pathological types via histopathology or cytopathology, including squamous cell carcinoma, undifferentiated carcinoma, neuroendocrine carcinoma, etc. For mixed pathological types, eligibility is determined by the predominant component; patients are eligible only if a pathologist confirms the adenocarcinoma component accounts for more than 70%. Patients with primary appendiceal tumors are excluded.
Presence of distant metastases at sites other than the liver.
Prior systemic treatment with anti-PD-1, anti-PD-L1, anti-CTLA-4 antibodies or other immunotherapeutic agents, or the CAPOX regimen. Prior radiotherapy for liver metastases, or prior radiation exposure to normal liver tissue adjacent to the planned irradiation field.
History of other malignant tumors within 5 years prior to enrollment, except cured carcinoma in situ of the cervix, basal cell or squamous cell skin cancer, radically treated localized prostate cancer, and radically treated ductal carcinoma in situ.
Fujian Medical University
Lead sponsor