Combining Cadonilimab and Regorafenib for treating colorectal liver metastasis

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 testing whether combining Cadonilimab and Regorafenib can help people with colorectal cancer that has spread to the liver after other treatments have not worked.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 44 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Fudan University (Academic / other)
• Drugs / interventions: bevacizumab, cetuximab, panitumumab, cadonilimab, fruquintinib, immunotherapy, Candonilimab
• Locations: 3 sites (Suzhou, Jiangsu and 2 other locations)
• Trial ID: NCT06455254 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the safety and efficacy of Cadonilimab (AK104), a bispecific antibody targeting PD-1 and CTLA-4, in combination with Regorafenib for patients with mismatch repair-proficient colorectal cancer that has metastasized to the liver. It is a single-arm, open-label, multicenter study focusing on patients who have previously failed second-line treatments. The study aims to assess treatment outcomes and explore potential biomarkers related to efficacy.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 75 with confirmed MSS colorectal cancer and liver metastases who have progressed after prior systemic therapies.

Not a fit: Patients with mismatch repair-deficient colorectal cancer or those who have not progressed after previous treatments may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with advanced colorectal liver metastasis who have limited treatment choices.

How similar studies have performed: While the combination of immunotherapy and targeted therapy is a growing area of interest, this specific combination of Cadonilimab and Regorafenib is novel and has not been extensively tested in prior studies.

Eligibility criteria

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.

Where this trial is running

Suzhou, Jiangsu and 2 other locations

• The First Affiliated Hospital of Soochow University — Suzhou, Jiangsu, China (Recruiting)
• Huashan Hospital — Shanghai, China (Recruiting)
• Shanghai Tenth People's Hospital — Shanghai, China (Recruiting)

Study contacts

• Study coordinator: Jinhong Chen, M.D

Conditions CRC