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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Intrahepatic Cholangiocarcinoma
• Intervention / Treatment: Drug: Cadonilimab+Gem/Cis

• Study Type: Interventional
• Enrollment (Estimated): 64
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 20043
      • Eastern hepatobilliary surgery hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Histologically or cytologically diagnosed intrahepatic cholangiocarcinoma (ICC)
2. At least 1 measurable lesion (according to RECIST1.1)
3. Have not previously received any systemic treatment
4. Age 18-75 years old, both male and female
5. ECOG performance status score (PS score) 0-2 point
6. Adequate medullary hematopoiesis function: Neutrophils≥1.5*10^9/L; platelets≥100*10^9/L
7. Adequate renal function: creatinine clearance > 60ml/min
8. Adequate hepatic function: Bilirubin ≤ 1.5 times the upper limit of normal
9. No cardiac insufficiency or chest pain (medically uncontrollable); no myocardial infarction in the 12 months prior to study initiation
10. Expectation survival time over 3 months
11. The patient must sign an informed consent form

Exclusion Criteria:

1. History of another primary malignancy
2. Brain metastases or spinal cord compression
3. Uncontrolled intercurrent illness
4. Have active or previously recorded autoimmune or inflammatory diseases (eg Rheumatoid arthritis, psoriasis, systemic lupus erythematosus, AIDS, etc)
5. Have received allogeneic organ transplantation
6. 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
7. History of active primary immunodeficiency
8. Pregnant or lactating women
9. Severe or uncontrolled infections
10. Patients with history of severe neurological or psychiatric illness, including dementia or epilepsy;
11. Patients with drug abuse, medical, psychological or social conditions that may interfere with the study results or the assessment of the study results;
12. Patients are unsuitable for the enrollment according to investigator's judgement.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Cadonilimab+Gem/Cis

Drug: Cadonilimab+Gem/Cis; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Shen Feng

Study record dates

Study Major Dates

• Study Start (Actual): November 24, 2022
• Primary Completion (Estimated): December 1, 2023
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: February 20, 2023
• First Submitted That Met QC Criteria: March 22, 2023
• First Posted (Actual): March 23, 2023

Study Record Updates

• Last Update Posted (Actual): November 2, 2023
• Last Update Submitted That Met QC Criteria: October 31, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: cadonilimab (anti-PD-1/CTLA-4 bispecific antibody)
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Cholangiocarcinoma
• Other Study ID Numbers: EHBHKY2022-H039-P001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No