Cadonilimab Combined With Regorafenib as A Third-line Treatment in Patients With MSS CRLM

July 27, 2024 updated by: Jin-hong Chen

A Single-arm, Multicenter, Phase II Study to Evaluate the Efficacy and Safety of Candonilimab（AK104） Combined With Regorafenib For the Third-line Treatment of MSS Colorectal Liver Metastasis

This study is a single-arm, open-label, multicenter clinical study to evaluate the efficacy and safety of Candonilimab (AK104) combined with Regorafenib for the treatment of MSS colorectal liver metastasis. Candonilimab (AK104) is a humanized IgG1 bispecific antibody that targets PD-1 and CTLA-4.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This is a single-arm, open-label, multicenter clinical study to evaluate the efficacy and safety of Candonilimab (AK104) combined with Regorafenib for the treatment of MSS colorectal liver metastasis. The purpose of the study is to observe and evaluate the efficacy and safety of Cadonilimab in combination with Regorafenib in patients with CRLM who had failed the previous second-line standard regimen, and to explore biomarkers related to efficacy.

Study Type

Interventional

Enrollment (Estimated)

44

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • China
      • Shanghai, China, 200072
        • Recruiting
        • Shanghai Tenth People's Hospital
        • Contact:
          • Chengle Zhuang, M.D
          • Phone Number: 19921618250
      • Shanghai, China, 200040
        • Recruiting
        • Huashan Hospital
        • Contact:
        • Contact:
        • Principal Investigator:
          • Jinhong Chen, M.D
        • Sub-Investigator:
          • Xiangyu Wang, M.D
        • Sub-Investigator:
          • Yan Geng, M.D
    • Jiangsu
      • Suzhou, Jiangsu, China, 215006
        • Recruiting
        • The First Affiliated Hospital of Soochow University
        • Contact:
          • Songbing He, M.D
          • Phone Number: 13812613662

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Age > 18 years old and < 75 years old;
  • ECOG Performance status score 0 or 1;
  • Histologically or cytologically confirmed adenocarcinoma of colon or rectum, with liver metastases, with or without extrahepatic metastases;
  • At least one measurable lesion as defined by RECIST version 1.1;
  • Progressed or be intolerant to prior systemic therapy including fluoropyrimidines, irinotecan, oxaliplatin, bevacizumab and/or cetuximab/panitumumab (if RAS/RAF-wild-type);
  • Known RAS and BRAF status;
  • Only patients with mismatch repair-proficient (pMMR)/microsatellite stable (MSS) status;
  • Adequate bone-marrow, liver, and renal function as assessed by the following laboratory requirements conducted within 7 days of starting to study treatment:

Liver and renal function: Total bilirubin ≤ 1.5× ULNl; aspartate transaminase (AST), alanine transaminase (ALT) ≤ 5× ULN; Serum creatinine ≤ 1.5× ULN; Bone-marrow function: Neutrophil count ≥ 1.5×10^9/L, Hemoglobin (Hb) ≥ 9.0 g/dL, Platelet count ≥ 100×10^9/L; International normalised ratio (INR) and partial thromboplastin time (PTT) ≤1.5 × ULN. Subjects who are therapeutically treated with an agent such as warfarin or heparin will be allowed to participate provided that no prior evidence of an underlying abnormality in coagulation parameters exists. Close monitoring of at least weekly evaluations will be performed until INR and PTT are stable based on a pre-dose measurement as defined by the local standard of care；

  • Patients of childbearing potential must be willing to use highly effective contraception for the duration of the study and for ≥120 days after the last dose of cadonilimab; female patients with a negative urine or serum pregnancy test result within ≤3 days prior to the first dose of the drug;
  • Able to understand and voluntarily sign written informed consent;
  • No history of allergy to regorafenib, cadonilimab and its components.

Exclusion Criteria:

  • Women who are pregnant or breastfeeding;
  • Patients who have previously been treated with third-line regimens such as regorafenib, fruquintinib, trifluridine tipiracil, or other immune checkpoint inhibitors, including anti-PD-1, anti-PD-L1, anti-CTLA-4, or any cellular immunotherapy;
  • Active autoimmune disease requiring systemic therapy within the past 2 years (e.g., treatment with disease-modifying drugs, corticosteroids, immunosuppressants), replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid therapy for adrenal or pituitary insufficiency) is not considered a systemic treatment;
  • Active or prior history of definite inflammatory bowel disease (such as Crohn's disease, ulcerative colitis, or chronic diarrhea);
  • Patients who have received intervention, ablation or radiotherapy within the previous 3 months for the target lesion;
  • Patients with an expected survival time of less than 3 months;
  • Study participants with other malignant tumors within 3 years prior to enrollment, excluding cured local tumors (such as basal cell skin cancer, squamous cell skin cancer, superficial bladder cancer, cervical carcinoma in situ, etc.);
  • Patients with severe psychological or psychiatric abnormalities;
  • No history of severe arrhythmia, heart failure, severe ventilatory dysfunction and severe lung infection, no acute and chronic renal failure;
  • Concurrent enrollment in another clinical study, unless it is an observational, non-interventional clinical study or a follow-up period of an interventional study;
  • Any other clinically significant disease or condition that, in the opinion of the investigator, may affect adherence to the protocol, or the signing of the Informed Consent Form (ICF) by the subject, or make participation in this clinical trial inappropriate.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Treatment arm
Candonilimab (AK104) + Regorafenib
Drug: Candonilimab (AK104)
Cadonilimab (AK104): 6mg/kg, i.v. q2w.
Drug: Regorafenib
Regorafenib: 80 mg p.o. qd for 3 weeks of every 4 week cycle (i.e. 3 weeks on, 1 week off).

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective Response Rate (ORR)
Time Frame: 6 months
ORR, determined using RECIST v1.1, defined as best overall response (CR or PR) across all assessment time points during the period from enrolment to termination of trial treatment.
6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Disease Control Rate (DCR)
Time Frame: 6 months
DCR, determined using RECIST v1.1, defined as the percentage of subjects whose best response was not PD (= total number of CR + PR + SD; CR, PR, or SD had to be maintained for at least 28 days from the first demonstration of that rating)
6 months
Duration of response (DoR)
Time Frame: 6 months
DoR, determined using RECIST v1.1, defined as the time from the first judgment of CR or PR to the discovery of PD after treatment.
6 months
Progression-free Survival (PFS)
Time Frame: 6 months
PFS, defined as the time from randomization to the first occurrence of disease progression as determined by the investigator with use of RECIST v1.1 or death from any cause, whichever occurs first.
6 months
Overall survival (OS)
Time Frame: 2 years
OS is defined as the time from date of randomization to death due to any cause. Subjects still alive at the time of analysis were censored at their last date of last contact.
2 years
Adverse event incidence rate (AE rate)
Time Frame: 6 months
Safety variables will be summarized using descriptive statistics based on adverse events collection.
6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Jin-hong Chen

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 11, 2024

Primary Completion (Estimated)

December 1, 2025

Study Completion (Estimated)

June 1, 2026

Study Registration Dates

First Submitted

June 7, 2024

First Submitted That Met QC Criteria

June 7, 2024

First Posted (Actual)

June 12, 2024

Study Record Updates

Last Update Posted (Actual)

July 30, 2024

Last Update Submitted That Met QC Criteria

July 27, 2024

Last Verified

July 1, 2024

More Information

Terms related to this study

Other Study ID Numbers

  • REGOCADO01

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Data are available from the corresponding author on reasonable request.

IPD Sharing Time Frame

Up to 1 year after the end of the study.

IPD Sharing Access Criteria

Applicants contact researchers by email to obtain data.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on CRC

Clinical Trials on Candonilimab (AK104)

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Panama

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe