More than half of colorectal cancer (CRC) patients present with RAS mutations or right-sided primary tumors; however, objective response rates (ORRs) to bevacizumab combined with chemotherapy remain suboptimal. Additionally, approximately 95% of metastatic CRC (mCRC) cases are microsatellite stable (MSS), where immune checkpoint inhibitor monotherapy demonstrates limited efficacy, necessitating combination strategies. Iparomlimab/tuvonralimab is the first bifunctional combination of anti-PD-1/anti-CTLA-4 monoclonal antibodies, which has shown therapeutic promise in first-line mCRC when combined with bevacizumab and capecitabine plus oxaliplatin (CAPEOX). Nevertheless, whether improved treatment response rates in mCRC patients can lead to higher surgical conversion rates remains unclear. This study evaluates the efficacy and safety of iparomlimab/tuvonralimab combined with bevacizumab and CAPEOX as conversion therapy in patients with right-sided or RAS-mutant, MSS, initially unresectable colorectal cancer liver metastasis.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
54
5mg/kg intravenous infusion on Day 1 of each cycle (every 21 days). Duration: 3 or 6 cycles
Bevacizumab: 7.5mg/kg intravenous infusion on Day 1 of each cycle (every 21 days). Capecitabine: 1000 mg/m2 twice daily orally on Day 1-14 of each cycle (every 21 days). Oxaliplatin: 130 mg/m2 intravenous infusion on Day 1 of each cycle (every 21 days). Duration: Conversion therapy phase: 3 or 6 cycles; Postoperative follow-up phase (for patients with successful conversion surgery ): 3 or 6 cycles (a total perioperative duration of 9 cycles); Maintenance phase (for patients without successful conversion surgery ): Continuous therapy until disease progression, intolerable adverse events, withdrawal of consent, loss to follow-up, death, or study termination.
After 3 or 6 cycles of conversion therapy, surgical resection ± ablation or stereotactic radiotherapy will be provided if applicable.
Peking University Cancer Hospital & Institute
Beijing, Beijing Municipality, China
Objective Response Rate
The proportion of subjects achieving complete response or partial response, assessed by investigators according to RECIST 1.1 criteria.
Time frame: Following 3 or 6 cycles (each cycle is ~21 days) of the treatment, approximately 9 or 18 weeks overall
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.
Time frame: Following 3 or 6 cycles (each cycle is ~21 days) of the treatment, approximately 9 or 18 weeks overall
Major Pathological Response Rate
The proportion of subjects in whom postoperative pathological evaluation of liver metastases shows either no residual tumor cells (complete regression) or residual tumor cells comprising 1-49% of the specimen.
Time frame: Perioperative/Periprocedural
Progression-free Survival
The time from the initiation of treatment until disease progression or death from any cause, whichever occurs first.
Time frame: From the date of treatment initiation until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 18 months
Overall Survival
The time from the initiation of treatment until death from any cause.
Time frame: From the date of treatment initiation until the date of death from any cause, assessed up to 18 months
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