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Biliary Tract CancerPhase 1/2NCT05994001

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

A Phase 1/2 study testing cardonilizumab and LM-302 in people with Biliary Tract Cancer and Candonilimab, run by Shanghai Zhongshan Hospital at 1 site in China.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Biliary Tract Cancer, Candonilimab, Claudin 18.2
What is being tested?
cardonilizumab and LM-302
Could I receive a placebo?
No, everyone receives an active treatment
How many people
78 participants
Where
1 siteChina
Study dates
1 Aug 2023to 1 Dec 2026
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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;
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  • 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.

Who cannot join

  • 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.

Trial locations and contacts

1 site in 1 country.

China1 site

  • Zhongshan hospital, Fudan University

    Shanghai

Other trials in China

About this study

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

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.

Read the 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.

Being tested
cardonilizumab, LM-302
Medical subject headings
Biliary Tract Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • cardonilizumabDrug

    Also called PD1 and CTLA-4 bispecific antibody

    cardonilizumab:PD1 and CTLA-4 bispecific antibody

  • LM-302Drug

    Also called ClAUDIN 18.2-ADC

    LM-302 :ClAUDIN 18.2-ADC

Study groups in NCT05994001
Study groupRoleWhat they receive
Group 1Experimental6 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.
Receives: Drug: cardonilizumab
Group 2Experimental1.8mg /mg LM-302 was treated for 1 course for 14 days.
Receives: Drug: LM-302
Group 3Experimental6 mg/kg cardonilizumab for 14 days was a course of treatment; RP2D LM-302 is 1 course of treatment for 14 days
Receives: Drug: cardonilizumab; Drug: LM-302

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. ORR(Phase II)

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

    Measured: 24months

  2. Incidence of Treatment-Emergent Adverse Events(Phase I)

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

    Measured: 24months

Secondary outcomes (3)

  1. DOR

    duration of overall response

    Measured: 24months

  2. DCR

    disease control rate

    Measured: 24months

  3. OS

    Overall survival

    Measured: 24months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Aug 2023
  2. Study start1 Aug 2023
  3. Primary completion1 May 2026
  4. Study completion1 Dec 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
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.
Masking
Single blind
Who is masked
Participant
Enrolment
78 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05994001
Sponsor's protocol ID
ZSAB-Calm
Status last verified
Sep 2026
First submitted
21 Jul 2023
Last updated
15 Sep 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 37075781

  • 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.

    PubMed 35278356

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing cardonilizumab and LM-302 in people with Biliary Tract Cancer and Candonilimab, run by Shanghai Zhongshan Hospital at 1 site in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 15 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

ORR(Phase II) (time frame: 24months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05994001, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Sep 2026.

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