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

NCT05994001 | Active Not Recruiting Phase 1

• 1 other identifier: ZSAB-Calm
• Study Type: interventional
• Target: 78
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Candonilimab; Claudin 18.2; Biliary Tract Cancer

Outcome Measures

Primary Outcomes (2)

• ORR(Phase II)

  Objective response rate (ORR) in patients with Claudin18.2-positive treated with cardonillizumab combined with LM302 (RECIST 1.1)(Phase II)

  24months

• Incidence of Treatment-Emergent Adverse Events(Phase I)

  Safety of cardonilizumab in combination with different doses of LM-302 in patients with advanced BTC

  24months

Secondary Outcomes (3)

• DOR

  24months

• DCR

  24months

• OS

  24months

Study Arms (3)

Group 1

EXPERIMENTAL

6 mg/kg cardonilizumab, 14 days for 1 course. Group 1 (6 mg/kg cadoniliamab) was closed due to no PR or CR achieved in 11 enrolled patients.

Drug: cardonilizumab

Group 2

EXPERIMENTAL

1.8mg /mg LM-302 was treated for 1 course for 14 days.

Drug: LM-302

Group 3

EXPERIMENTAL

6 mg/kg cardonilizumab for 14 days was a course of treatment; RP2D LM-302 is 1 course of treatment for 14 days

Drug: cardonilizumab; Drug: LM-302

Interventions

cardonilizumab DRUG

cardonilizumab:PD1 and CTLA-4 bispecific antibody

Also known as: PD1 and CTLA-4 bispecific antibody

Group 1; Group 3

LM-302 DRUG

LM-302 :ClAUDIN 18.2-ADC

Also known as: ClAUDIN 18.2-ADC

Group 2; Group 3

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).
• Failure of standard chemotherapy (gemcitabine or platinum or fluorouracil) and PD1/PD-L1 for advanced BTC due to disease progression or toxicity;
• Measurable lesions;
• 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;
• ECOG physical state ≤ 2;
• Life expectancy \> 3 months;
• Adequate renal function: creatinine (Cr) ≤ 1.5 × upper limit of normal (ULN) or glomerular filtration rate (GFR) ≥ 60mL/min/ 1.73m2;
• Adequate liver function: bilirubin ≤ 1.5 × ULN and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN;
• Adequate bone marrow reserve: absolute value of neutrophil (ANC) \> 1500/mcl, platelets (Plts) \> 75,000/mcl, hemoglobin (Hgb) ≥ 9.0g/dl;
• Prothrombin time/activated partial thromboplastin time (PT/PTT) \<1.5 × ULN;
• Age ≥18 years old, male or female;
• Participants with a prior history or persistent hepatitis C virus (HCV) infection will be eligible to participate in the study. Participants receiving antiviral therapy must complete treatment at least 1 month before the start of the study intervention. For HCV subjects who have not received or have not completed antiviral therapy, treatment should be initiated only after liver function has remained stable for at least 3 months during the study intervention.
• Hepatitis B controlled subjects are eligible to participate in the study as long as they meet the following criteria:
• Subjects with chronic hepatitis B virus (HBV) infection (defined as hepatitis B surface antigen \[HBsAg\] positive and/or detectable HBV DNA) must have a HBV viral load of less than 2000 IU/ml prior to first dosing of the study intervention or a 10-fold reduction in HBV viral load with antiviral therapy. Subjects treated with active HBV with a viral load below 2000 IU/ml should receive antiviral therapy throughout the study intervention.
• Subjects who are clinically cured of HBV infection (defined as HBsAg negative and anti-HBC positive) and whose HBV viral load is not detectable at screening should have their HBV viral load checked every 8 weeks and should be treated for HBV if the viral load exceeds 2000 IU/ml. Antiviral therapy after completion of the study intervention should follow local guidelines.

You may not qualify if:

• \) 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.

Sponsors & Collaborators

• Shanghai Zhongshan Hospital: lead

Study Sites (1)

Zhongshan hospital, Fudan University

Shanghai, China

Location

Related Publications (2)

• Kelley RK, Ueno M, Yoo C, Finn RS, Furuse J, Ren Z, Yau T, Klumpen HJ, Chan SL, Ozaka M, Verslype C, Bouattour M, Park JO, Barajas O, Pelzer U, Valle JW, Yu L, Malhotra U, Siegel AB, Edeline J, Vogel A; KEYNOTE-966 Investigators. Pembrolizumab in combination with gemcitabine and cisplatin compared with gemcitabine and cisplatin alone for patients with advanced biliary tract cancer (KEYNOTE-966): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2023 Jun 3;401(10391):1853-1865. doi: 10.1016/S0140-6736(23)00727-4. Epub 2023 Apr 16.

  PMID: 37075781 BACKGROUND

• Oh DY, Lee KH, Lee DW, Yoon J, Kim TY, Bang JH, Nam AR, Oh KS, Kim JM, Lee Y, Guthrie V, McCoon P, Li W, Wu S, Zhang Q, Rebelatto MC, Kim JW. Gemcitabine and cisplatin plus durvalumab with or without tremelimumab in chemotherapy-naive patients with advanced biliary tract cancer: an open-label, single-centre, phase 2 study. Lancet Gastroenterol Hepatol. 2022 Jun;7(6):522-532. doi: 10.1016/S2468-1253(22)00043-7. Epub 2022 Mar 9.

  PMID: 35278356 BACKGROUND

MeSH Terms

Conditions

Biliary Tract Neoplasms

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Biliary Tract Diseases; Digestive System Diseases

Study Officials

• Jia Fan, MD

  Fudan University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Each cycle of the first phase was defined as cardonilizumab (6mg/kg,Q2W) combined with different concentrations of 1.6mg/kg or 1.8mg/kg LM-302 (Q2W), 14 days as a course of treatment, and the combined dose (RP2D) of LM-302 during combination therapy was determined according to the 3+3 design. In the second phase, Claudin18.2 expression was positive, and the positive population was randomly assigned to trial group 1, trial group 2, and trial group 3. Group 1:6 mg/kg cardonilizumab, 14 days for 1 course. Group 2:1.8mg /mg LM-302 was treated for 1 course for 14 days. Group 3: 6 mg/kg cardonilizumab for 14 days was a course of treatment; RP2D LM-302 is 1 course of treatment for 14 days.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Each cycle of the first phase was defined as cardonilizumab (6mg/kg,Q2W) combined with different concentrations of 1.6mg/kg or 1.8mg/kg LM-302 (Q2W), 14 days as a course of treatment, and the combined dose (RP2D) of LM-302 during combination therapy was determined according to the 3+3 design. In the second phase, Claudin18.2 expression was positive, and the positive population was randomly assigned to trial group 1, trial group 2, and trial group 3. Group 1:6 mg/kg cardonilizumab, 14 days for 1 course. Group 2:1.8mg /mg LM-302 was treated for 1 course for 14 days. Group 3: 6 mg/kg cardonilizumab for 14 days was a course of treatment; RP2D LM-302 is 1 course of treatment for 14 days.

Study Record Dates

• First Submitted: July 21, 2023
• First Posted: August 16, 2023
• Study Start: August 1, 2023
• Primary Completion: May 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: February 18, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)