Cadonilimab Combined With Gem/Cis as First Line Therapy in Patients With Advanced ICC

Study Overview
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Brief Summary
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TOPAZ-1 phase III trail demonstrated that the addition of immune checkpoint inhibitor anti-PD-L1 antibody improved progression-free survival (PFS) and overall survival (OS) compared to Gem/Cis alone. Cadonilimab is a first-in-class bispecific, humanized IgG1 antibody targeting PD-1 and CTLA-4, which has the potential to boost immune surveillance in tumors. The goal of this clinical trial is to evaluated the efficacy and safety of cadonilimab combined with gemcitabine and cisplatin as first Line therapy in patients with advanced intrahepatic cholangiocarcinoma. Eligible participants will receive cadonilimab (up to 12 months) plus gemcitabine and cisplatin (for maximum of 6-8 cycles) until radiologic disease progression, unacceptable toxicity, or withdrawal from the study, whichever occurred first. The primary endpoint is objective response rate.

Official Title
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Cadonilimab Combined With Gemcitabine and Cisplatin as First Line Therapy in Patients With Advanced Intrahepatic Cholangiocarcinoma: A Single Center, Single Arm, Phase II Trial

Conditions
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Intrahepatic Cholangiocarcinoma

Intervention / Treatment
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* Drug: Cadonilimab+Gem/Cis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically diagnosed intrahepatic cholangiocarcinoma (ICC) At least 1 measurable lesion (according to RECIST1.1) Have not previously received any systemic treatment Age 18-75 years old, both male and female ECOG performance status score (PS score) 0-2 point Adequate medullary hematopoiesis function: Neutrophils≥1.5*10^9/L; platelets≥100*10^9/L Adequate renal function: creatinine clearance > 60ml/min Adequate hepatic function: Bilirubin ≤ 1.5 times the upper limit of normal No cardiac insufficiency or chest pain (medically uncontrollable); no myocardial infarction in the 12 months prior to study initiation Expectation survival time over 3 months The patient must sign an informed consent form Exclusion Criteria: History of another primary malignancy Brain metastases or spinal cord compression Uncontrolled intercurrent illness Have active or previously recorded autoimmune or inflammatory diseases (eg Rheumatoid arthritis, psoriasis, systemic lupus erythematosus, AIDS, etc) Have received allogeneic organ transplantation Control of concurrent complications, including but not limited to persistent or active infections, symptomatic congestive heart failure, poorly controlled hypertension, unstable angina, poorly controlled arrhythmia, active interstitial lung disease ( ILD), severe chronic gastrointestinal disorders associated with diarrhea symptoms, may limit compliance with the psychiatric/social conditions required by the trial, and substantially increase the risk of adverse events or affect the ability of patients to sign written consent forms History of active primary immunodeficiency Pregnant or lactating women Severe or uncontrolled infections Patients with history of severe neurological or psychiatric illness, including dementia or epilepsy; Patients with drug abuse, medical, psychological or social conditions that may interfere with the study results or the assessment of the study results; Patients are unsuitable for the enrollment according to investigator's judgement.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cadonilimab+Gem/Cis<br> | Drug: Cadonilimab+Gem/Cis<br>* Cadonilimab (500mg, iv, Q3W, Day1) with gemcitabine(1000mg/m^2, iv, Q3W, Day1and Day8) plus cisplatin(25mg/m^2, iv, Q3W, Day1and Day8) up to 8 cycles followed by cadonilimab (500mg, iv, Q3W, Day1) plus capecitabine（1000 mg/m^2 orally according to Body Surface Area (BSA)，BID，Q3W，on Days 1-14）as maintenance therapy until disease progression or other discontinuation criteria, up to 24months.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate (ORR) per RECIST 1.1 | Defined as patients achieving a complete response [CR] or partial response [PR] | Up to two years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival (PFS) per RECIST 1.1 | Defined as the time from the start of treatment to the date of progressive disease, or death, whichever occurred first. | Up to two years | 
| Desease control rate (DCR) per RECIST 1.1 | CR + PR + SD | Up to two years | 
| Overall survival (OS) | Defined as the time from the start of treatment to the date of death from any cause | Up to two years | 
| 6mo PFS rate per RECIST 1.1 | Progression-free survival (PFS) rate at 6 months | at 6 months | 
| adverse events | Include Treatment emerge adverse events, treatment related adverse events and serious adverse events | Up to two years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cadonilimab (anti-PD-1/CTLA-4 bispecific antibody)