Neoplasms

All Conditions

Rare Diseases

Cholangiocarcinoma

Adenocarcinoma

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Bile Duct Cancer

Intrahepatic Cholangiocarcinoma

Antineoplastic Agents

All Drugs and Chemicals

Gemcitabine

Oxaliplatin

Lenvatinib

Protein Kinase Inhibitors

Enzyme Inhibitors

Patients with advanced intrahepatic cholangiocarcinoma who was initially evaluated unsuitable for the radical therapy and received combined HAIC plus lenvatinib (Len) and pucotenlimab as conversion therapy for downstaging.

administration of gemcitabine and oxaliplatin via the tumor feeding arteries every 3 weeks.

HAIC

lenvatinib (8mg, qd) plus pucotenlimab (200mg, q3w)

Lenvatinib plus pucotenlimab

Ze-yang Ding

Han Gao

Ze-yang Ding, M.D.

This is an open-label, single-arm, phase 2 study. The purpose of study is to evaluate the feasibility and safety of hepatic artery infusion chemotherapy combined with lenvatinib and pucotenlimab as conversion therapy for unresectable intrahepatic cholangiocarcinoma.

Pucotenlimab is a new humanized PD-1-specific monoclonal antibody. On September 29, 2022, the National Medical Products Administration of China approved the marketing application of Pucotenlimab Injection for the treatment of patients with microsatellite highly unstable (MSI-H)/mismatch repair function defective (dMMR) solid tumors who have failed prior first-line and above systemic therapy. There have been studies and reports on systemic chemotherapy with GEMOX regimen combined with lenvatinib and PD-1 monoclonal antibody for the treatment of intrahepatic cholangiocarcinoma. Currently, a multicenter, phase 2 study evaluating the efficacy of pucotenlimab in patients with mismatch repair-deficient (dMMR) or microsatellite instabilityhigh (MSI-H) tumors is underway. The objective response rate (ORR) is 49.0% (95% CI 38.86%-59.20%), while the median progression-free survival and overall survival have not been reached. Grade ≥3 treatment-related adverse events were observed in 18 of 100 patients. The efficacy of this antibody in patients is promising. Based on the results of these previous studies, this study intends to evaluate the efficacy and safety of hepatic artery infusion chemotherapy (GEMOX regimen) combined with lenvatinib and pucotenlimab in the down-stage conversion treatment of patients with unresectable intrahepatic cholangiocarcinoma.

Combined HAIC, Lenvatinib and Pucotenlimab as Conversion Therapy for Unresectable Intrahepatic Cholangiocarcinoma

A Phase 2, Open-label, Single Arm Study of Combined HAIC, Lenvatinib and Pucotenlimab as Conversion Therapy for Unresectable Intrahepatic Cholangiocarcinoma

Number of patients amendable to curative surgical interventions defined as number of patients receiving curative surgical resection, transplantation, or ablation after successful down-sizing of tumor(s) by intervention.

Complete response (CR): Disappearance of any intra-tumoral arterial enhancement in all target lesions; Partial response (PR): At least a 30% decrease in the sum of diameters of viable (enhancement in the arterial phase) target lesions, taking as reference the baseline sum of the diameters of target lesions; Stable disease (SD): Any cases that do not qualify for either partial response or progressive disease; Progressive disease (PD): An increase of at least 20% in the sum of the diameters of viable (enhancing) target lesions, taking as reference the smallest sum of the diameters of viable (enhancing) target lesions recorded since treatment started.

measured from date of first treatment to the date of death from any cause. Participants alive or lost to follow-up will be censored at the date of their last visit.

measured from the date of first treatment to radiographically documented progression according to mRECIST 1.1 or death from any cause (whichever occurs first). Participants alive and without disease progression or lost to follow-up will be censored at the date of their last radiographic assessment.

Time to progression (TTP): measured from the date of first treatment to radiographically documented progression according to mRECIST 1.1. This does not include death from any cause.

Time to intrahepatic tumor progression (TTITP): measured from the date of first treatment to radiographically documented intrahepatic tumor progression according to mRECIST 1.1. This does not include death from any cause.

Incidence, nature, and severity of adverse events graded according to the United States National Cancer Institute The Common Terminology Criteria for Adverse Events (NCI-CTCAE 5.0)

Pathological response is assessed as the percentage of surface with non-viable cancer cells (represented by necrosis or fibrosis, the ultimate stage of necrosis) in relation to the total tumor area and will be equal to: 100% - viable cancer cells (%). If there are multiple tumors, the mean percentage will be used.

percentage of patients with CR, PR, or stable disease (SD) ≥6 months based on mRECIST

Defined as the time from first documented evidence of CR or PR until the first documented sign of disease progression (PD) or death from any cause

The life quality of every subject is assessed every 3 months during follow up according to the 45-item FACT-Hep questionnaire, which assesses generic HRQL concerns and disease-specific issues.

Spots Global Cancer Trial Database for lenvatinib plus pucotenlimab