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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 | Clinical Trials | Clareo Health

ACTIVE_NOT_RECRUITINGPHASE1/PHASE2

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

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

NCT05994001•Shanghai Zhongshan Hospital

View on ClinicalTrials.gov

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.

Detailed 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.

Eligibility

Age

18 - No limit years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•1. Advanced BTC that is not resectable or metastatic or recurred after surgery, histologically confirmed, and sufficient tissue specimens are provided for PD-L1, CTLA-4, Claudin18.2 immunohistochemistry and exon sequencing. Claudin18.2 expression is not required at the first stage. In the second stage, Claudin18.2-positive patients were required to be enrolled (≥40% immunohistochemical expression of Claudin18.2 was considered positive, \<40% was considered negative, and two independent pathologists made the judgment. If there was any discrepancy, the third pathologist was asked to make the judgment together).
•2. Failure of standard chemotherapy (gemcitabine or platinum or fluorouracil) and PD1/PD-L1 for advanced BTC due to disease progression or toxicity;
•3. Measurable lesions;
•4. For patients with a prior history of hepatic chemoembolization, radiofrequency ablation/intervention, or radiotherapy, measurable lesions outside the chemoembolization or radiotherapy area or measurable progression lesions at the chemoembolization or radiotherapy site must be present;
•5. ECOG physical state ≤ 2;
•6. Life expectancy \> 3 months;
•7. Adequate renal function: creatinine (Cr) ≤ 1.5 × upper limit of normal (ULN) or glomerular filtration rate (GFR) ≥ 60mL/min/ 1.73m2;
•8. Adequate liver function: bilirubin ≤ 1.5 × ULN and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN;
•9. Adequate bone marrow reserve: absolute value of neutrophil (ANC) \> 1500/mcl, platelets (Plts) \> 75,000/mcl, hemoglobin (Hgb) ≥ 9.0g/dl;
•10. Prothrombin time/activated partial thromboplastin time (PT/PTT) \<1.5 × ULN;
+5 more criteria

Exclusion Criteria

•1\) Previous treatment with checkpoint inhibitor CTLA-4 monoclonal antibody, targeting Claudin18.2; 2) Major surgery or radiotherapy or intervention or ablation within 4 weeks before enrollment; 3) Active, known, or suspected autoimmune disease; 4) Congestive heart failure or symptomatic coronary artery disease within 3 months prior to enrollment; 5) Cerebrovascular accident occurred within the past 6 months; 6) Clinically significant bleeding, bleeding event, or thromboembolic disease within 6 months; 7) History of intestinal perforation; 8) Have a history of (non-infectious) pneumonia requiring steroid treatment or currently have pneumonia; 9) Known history of human immunodeficiency virus (HIV) infection; 10) A history of severely impaired lung function or interstitial lung disease; 11) Concurrent malignancies (other than adequately treated non-melanoma skin cancer, superficial transitional cell carcinoma of the bladder and cervical carcinoma in situ \[CIS\]) or any currently active malignancies have been diagnosed within the last 5 years; 12) Past or current evidence indicates any condition, treatment, or laboratory abnormality that may confuse the study results, interfere with the subject's participation throughout the study, or the investigator determines that participation in the study is not in the subject's best interest.

Locations (1)

Zhongshan hospital, Fudan University

Shanghai, China

Key Dates

Start Date

August 1, 2023

Primary Completion Date

May 1, 2026

Completion Date

December 1, 2026

Last Updated

February 18, 2026

Enrollment

ACTUAL participants

Conditions

Biliary Tract CancerCandonilimabClaudin 18.2

Interventions

cardonilizumab

DRUG

LM-302

DRUG

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Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: February 18, 2026Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

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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

Inclusion Criteria

Exclusion Criteria

Study of Dato-DXd as Monotherapy and in Combination With Anti-cancer Agents in Patients With Advanced Solid Tumours (TROPION-PanTumor03)

Study of TJ033721 (Givastomig) in Subjects With Advanced or Metastatic Solid Tumors

Trifluridine/Tipiracil + Oxaliplatin in Participants With Advanced or Metastatic Biliary Tract Cancer

Cosiporfin Sodium for Injection Photodynamic Therapy

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An Exploratory Study on the Use of Ivosidenib for the Precise Treatment of Advanced Biliary Tract Malignancies With IDH1 Mutations in the Later Line of Therapy.