Candonilimab in Combination With LM-302 for Claudin 18.2 Positive-advanced Biliary Tract Cancer After Failure of Standard of Chemotherapy and PD1/PD-L1 Antibody

Biliary Tract Cancer Clinical Trial

Official title: Two Stage, Multi-center Trial of Candonilimab in Combination With LM-302 for Treatment of Patients With Claudin 18.2 Positive-advanced Biliary Tract Cancer After Failure of Standard of Chemotherapy and PD1/PD-L1 Antibody

Status Recruiting

Clinical Trial Summary

In this clinical study, we will evaluate the efficacy and safety of cardonilimumab (PD1 monoclonal antibody and CTLA-4 monoclonal antibody bisspecific antibodies) and LM-302 (Claudin18.2-ADC) in Claudin18.2-positive advanced BTC patients who have progressed after SOC and PD1/PD-L1 monoclonal antibody treatment.

Clinical Trial Description

The prognosis for unresectable and metastatic biliary malignancies (BTC) is extremely poor, with a median overall survival of only about 1 year for advanced biliary tumors treated with gemcitabine and cisplatin or combined with duvaliumab (PD-L1) as recommended by NCCN guidelines. At present, the NCCN guidelines recommend that the posterior line treatment of advanced BTC, such as FOLFOX, has a very limited effect, with an objective response rate of only about 5% and a median survival time of only about 6 months. There is an urgent need to develop new therapeutic methods to improve patient survival. Chronic inflammation caused by viral infection and bile duct stones are the most common potential risk factors for BTC, and immune system abnormalities play a key role in the occurrence and development of BTC. BTC, including intrahepatic cholangiocarcinoma (iCCA), showed abnormal expression of immune checkpoint molecules PD-L1 and CTLA-4 and obvious heterogeneity. Therefore, immunotherapy is of great value. TOPAZ-1 and KENOTE-966 studies both showed the value of PD-L1/PD1 monoclonal antibody in the treatment of advanced BTC. There is currently a lack of treatment options for progression after treatment with standard chemotherapy (SOC) combined with PD-L1/PD1 monoclonal antibodies. CTLA-4 inhibitors combined with PD-1/PD-L1 inhibitors have shown significantly enhanced clinical effects. Clinical studies on treating CTLA-4 inhibitors combined with PD-1/PD-L1 inhibitors have been carried out in several solid tumors. Although significant therapeutic effects have been achieved, adverse reactions (AEs) that cannot be ignored limit the benefit of patients. Claudin18.2 is a newly discovered tumor therapeutic target. Multiple clinical studies have shown that Claudin18.2 monoclonal antibody, Claudin18.2-ADC, and Cart-Claudin18.2 have good ORR in Claudin18.2-positive gastric cancer. At present, no independent research data on advanced BTC has been reported.

In this clinical study, we will evaluate the efficacy and safety of cardonilimumab (PD1 monoclonal antibody and CTLA-4 monoclonal antibody bispecific antibodies) and LM-302 (Claudin18.2-ADC) in Claudin18.2-positive advanced BTC patients who have progressed after SOC and PD1/PD-L1 monoclonal antibody treatment. ;

Related Conditions & MeSH terms

• Biliary Tract Cancer
• Biliary Tract Neoplasms

• NCT number: NCT05994001
• Study type: Interventional
• Source: Shanghai Zhongshan Hospital
• Contact: Guo-Ming Shi, MD
• Phone: +86-13916969578
• Email: shi.guoming@zs-hospital.sh.cn
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: August 1, 2023
• Completion date: August 1, 2026