Radiotherapy Combined QL1706, TAS-102 and Bevacizumab in mCRC

A Single-Arm, Exploratory Study of Palliative Radiotherapy Combined With Iparomlimab and Tuvonralimab, Trifluridine/Tipiracil (TAS-102), and Bevacizumab in Later-Line Treatment of Advanced Colorectal Cancer

This single-center, single-arm, prospective study plans to enroll patients with advanced colorectal cancer who have failed first-line or higher systemic therapies. Participants will receive a combination of iparomlimab and tuvonralimab (QL1706), trifluridine/tipiracil (TAS-102), bevacizumab, and palliative radiotherapy. The efficacy and safety of this combination therapy will be evaluated by assessing objective response rate (ORR), progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and safety profile.

Inclusion Criteria:

• Aged 18 to 75 years .
• Histologically confirmed unresectable colorectal adenocarcinoma.
• Patients must have received at least one prior line of oxaliplatin-, irinotecan-, or 5-FU-based therapy with documented progression or intolerance.
• Documented KRAS and BRAF mutation status (mutant or wild-type) must be available.
• Palliative radiotherapy targeting primary or metastatic lesions is planned.
• At least one measurable lesion per RECIST v1.1 exists.
• ECOG score of 0-1 and life expectancy ≥12 weeks.
• Adequate bone marrow, hepatic, and renal function must be demonstrated.
• Fertile patients commit to using effective contraception during and for 6 months post-treatment.

Exclusion Criteria:

• History of Grade ≥3 immune-related adverse events (irAEs) from prior immunotherapy deemed contraindications for retreatment.
• Radiation or systemic anticancer therapy within 14 days prior to first study treatment.
• Active CNS metastases and/or leptomeningeal disease (LMD). Symptomatic interstitial lung disease (ILD), active pneumonitis, uncontrolled infections, or non-healing wounds/fistulae.
• Intestinal perforation risks: active diverticulitis, intra-abdominal abscess, GI obstruction, or cancer-related peritoneal carcinomatosis.
• Uncontrolled or symptomatic serous cavity effusions (pleural, ascites, pericardial).
• Uncontrolled cardiovascular/cerebrovascular diseases.
• Medical/social conditions that may compromise study results or lead to premature termination per investigator judgment.