This study will evaluate the efficacy and safety of cryoablation combined with lenvatinib plus QL1706 (iparomlimab/tuvonralimab) in patients with advanced Intrahepatic Cholangiocarcinoma (ICC) who have progressed after first-line treatment.
Written informed consent obtained.
Age ≥ 18 years at time of study entry.
Participants must have unresectable or metastatic histologically or cytologically confirmed intrahepatic cholangiocarcinoma
Participants must have failed 1 line of systemic regimens for advanced cholangiocarcinoma due to disease progression or toxicity. Cohort A must have progressed after GemCis plus PD1/PD-L1 inhibitor. Cohort B must have progressed after GemCis plus PD1/PD-L1 inhibitor and anti-vascular endothelial growth factor antibody/tyrosine kinase inhibitors.
History of cardiac disease, including clinically significant gastrointestinal bleeding within 4 weeks prior to start of study treatment
Thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within the 6 months Prior to the first dose of study drug with the exception of thrombosis of a segmental portal vein.
Prior treatment with cryoablation.
RFA and resection administered less than 4 weeks prior to study treatment start.
Parallel
QL1706 (bispecific antibody targeting PD-1 and CLTA-4)
DrugQL1706 will be administered by IV, 5 mg/kg on day 1 of each 21 day cycle until documented disease progression, development of unacceptable toxicity, participant request, or withdrawal of consent.
Lenvatinib
DrugLenvatinib will be administered (bodyweight ≥ 60 kg, 12 mg; \< 60 kg, 8 mg) orally daily until documented disease progression, development of unacceptable toxicity, participant request, or withdrawal of consent.
cryoablation
Procedure/SurgeryCryoablation will be performed with a two-cycle freeze-thaw phase protocol; US or non-contrast CT images will be obtained to visualize the evolving ablation zone. Lenvatinib plus QL1706 will be administered 1-3 days after cryoablation.
Objective Response Rate (ORR) according to RECIST 1.1
ORR is defined as the percentage of participants who have a confirmed complete response (CR: disappearance of all target lesions) or partial response (PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters). Responses are according to RECIST 1.1 as assessed by investigator.
Disease control rate (DCR) evaluated by the investigator per Response Evaluation Criteria in Solid Tumors Version 1.1
DCR is defined as the proportion of patients with complete response (CR), partial response (PR) and stable disease (SD).
Duration of Response (DOR) evaluated by the investigator per Response Evaluation Criteria in Solid Tumors Version 1.1
DOR is defined as the time from first documented complete or partial response until disease progression, death from any cause, or censoring at date of last tumor assessment.
Time to Response (TTR) evaluated by the investigator per Response Evaluation Criteria in Solid Tumors Version 1.1
TTR is defined as the time from the start of treatment until the first objective observation of a response (either partial response, PR, or complete response, CR), provided that the response is subsequently confirmed.
Progression Free Survival (PFS) evaluated by the investigator per Response Evaluation Criteria in Solid Tumors Version 1.1
PFS is defined as the time from study treatment to disease progression or all-cause death as assessed by the investigator (whichever occurs first)
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