This is a single-center, open-label, exploratory phase II trial to evaluate efficacy and safety of Retlirafusp alfa (PD-L1/TGF-βRII bispecific fusion protein) combined with standard first-line targeted-chemotherapy as conversion therapy in adult patients with initially unresectable microsatellite-stable (MSS/pMMR) colorectal adenocarcinoma liver metastases. Two pre-defined cohorts are enrolled: Cohort 1 for RAS/BRAF wild-type left-sided primary tumor (mFOLFOX6 + cetuximab + Retlirafusp alfa); Cohort 2 for RAS/BRAF-mutant or right-sided primary tumor (CAPEOX + bevacizumab + Retlirafusp alfa).
Signed written informed consent before any trial-related procedure.
Age ≥18 and ≤79 years, male or female.
Histopathologically confirmed colorectal adenocarcinoma; liver metastasis confirmed by pathology or imaging.
No prior first-line systemic therapy (targeted, immunotherapy, systemic chemotherapy) specifically for liver metastases.
1. Inability to tolerate systemic chemotherapy or subsequent surgery. 2. Liver metastases occurring during or within 6 months after completion of oxaliplatin-based adjuvant chemotherapy for primary colorectal tumor.
Single group
Retlirafusp alfa Combined with Targeted Therapy and Chemotherapy
DrugCohort 1 (RAS/BRAF wild-type, left-sided primary colon cancer): * Retlirafusp alfa 1800 mg IV D1 every 3 weeks * Cetuximab 500 mg/m² IV D1 every 2 weeks * mFOLFOX6: Oxaliplatin 85 mg/m² IV D1 q2w; Leucovorin 400 mg/m² IV D1 q2w; 5-FU 400 mg/m² IV bolus D1 q2w plus 2400 mg/m² 48-h continuous infusion q2w. Cohort 2 (RAS/BRAF mutant OR RAS/BRAF wild-type right-sided primary colon cancer): * Retlirafusp alfa 1800 mg IV D1 every 3 weeks * Bevacizumab 7.5 mg/kg IV D1 every 3 weeks * CAPEOX: Oxaliplatin 130 mg/m² IV D1 q3w; Capecitabine 1000 mg/m² orally twice daily D1-14 q3w.
Objective Response Rate
The proportion of subjects achieving complete response or partial response, assessed by investigators according to RECIST 1.1 criteria.
Major Pathological Response Rate
Surgical Conversion Rate
The proportion of subjects with successful conversion surgery. The criteria for successful conversion are as follows: evaluation of liver metastases achieves partial response after the conversion therapy; liver tumor-free status can be achieved through surgical resection ± ablation or stereotactic radiotherapy, with a residual liver volume exceeding 40%; liver function is classified as Child-Pugh Class A, and other liver function and laboratory parameters meet surgical and anesthesia requirements.
Progression-free Survival
The time from the initiation of treatment until disease progression or death from any cause, whichever occurs first.
Overall Survival
Description: The time from the initiation of treatment until death from any cause.
Click on the lead sponsor to view all of their trials.
This trial is not recruiting at the moment. You can still explore other options:
