Clinical trial NCT06455254: Cadonilimab Combined With Regorafenib as A Third-line Treatment in Patients With MSS CRLM
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: CRC
Lead sponsor: Fudan University
Sponsor class: OTHER
First posted: 2024-06-12
Enrollment: 44
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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.

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.

Primary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: 6 months
Secondary outcomes:
measure: Disease Control Rate (DCR)
timeFrame: 6 months
measure: Duration of response (DoR)
timeFrame: 6 months
measure: Progression-free Survival (PFS)
timeFrame: 6 months
measure: Overall survival (OS)
timeFrame: 2 years
measure: Adverse event incidence rate (AE rate)
timeFrame: 6 months
Other outcomes:
Locations:
city: Suzhou
country: China
facility: The First Affiliated Hospital of Soochow University
state: Jiangsu
city: Shanghai
country: China
facility: Huashan Hospital
city: Shanghai
country: China
facility: Shanghai Tenth People's Hospital
Study officials:
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