This study is designed to evaluate the safety, tolerability, and efficacy of Epalolitovoreli Monoclonal Antibody (QL1706) combined with Fruquintinib and Short-Course Radiotherapy (SCRT), compared with standard third-line therapy, in the treatment of patients with unresectable liver-metastatic pMMR/MSS colorectal cancer.
Signed written informed consent, and ability to comply with the scheduled visits and related procedures as specified in the protocol.
Age ≥18 years and ≤75 years, male or female.
Histologically or cytologically confirmed metastatic colorectal cancer with unresectable liver metastasis(es) measuring ≥5 cm in the longest diameter.
Confirmed pMMR (proficient mismatch repair) or MSS (microsatellite stable) status by immunohistochemistry (IHC), next-generation sequencing (NGS), or PCR testing.
1. History of allergy to any study drug, including Epalolitovoreli Monoclonal Antibody and Fruquintinib.
Ventricular arrhythmias or other uncontrolled arrhythmias requiring medical intervention (e.g., antiarrhythmic medication).
Severe conduction disorders (e.g., third-degree atrioventricular block).
Heart rate-corrected QT interval (QTc, calculated using Fridericia's formula) ≥480 ms.
Parallel
QL1706 + Fruquintinib + Short-Course Ablative Radiotherapy (SCART)
DrugPatients will receive the PD-1/CTLA-4 bispecific antibody Epalolitovoreli Monoclonal Antibody (QL1706) at a dose of 5 mg/kg by intravenous infusion every 3 weeks (Q3W). Patients will concomitantly receive oral Fruquintinib once daily (QD). The dose will be determined in a Phase Ib dose-escalation phase exploring 3 mg and 4 mg QD levels, using a modified 3+3 design to establish the Recommended Phase II Dose (RP2D). Patients will undergo Short-Course Ablative Radiotherapy (SCART) to the liver metastasis/metastases. The prescribed dose is 15 Gy in 3 fractions to the Gross Tumor Volume (GTV) and 45-72 Gy in 3 fractions to the Subclinical Target Volume (STV). Treatment with QL1706 and Fruquintinib will continue until disease progression, unacceptable toxicity, or other protocol-specified discontinuation criteria.
Standard Third-Line Therapy
DrugPatients will receive one of the following standard-of-care third-line therapies for metastatic colorectal cancer, selected by the investigator based on the patient's prior treatment history and comprehensive condition: Cetuximab with or without Irinotecan (for patients not previously treated with cetuximab). Regorafenib. Fruquintinib. Trifluridine/Tipiracil (TAS-102) with or without Bevacizumab.
Progression Free Survival（PFS）
Progression-free survival (PFS) is defined as the time from the initiation of study treatment to the first occurrence of disease progression or death from any cause, whichever comes first.
Overall Survival
The time from the date of randomization to the death caused by any cause
dverse events (AEs) were graded according to the NCI CTCAE version 5·0
Adverse events and surgical safety
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Tao Zhang
Lead sponsor
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Sponsor institution
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