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

CRC Clinical Trial

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06455254
• Other study ID #: REGOCADO01
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: June 2024
• Est. completion date: June 2026

Study information

• Verified date: June 2024
• Source: Fudan University
• Contact: Jinhong Chen, M.D
• Phone: +8613801977742
• Email: jinhongch[@]hotmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 44
• Est. completion date: June 2026
• Est. primary completion date: December 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• No history of allergy to regorafenib, cadonilimab and its components;

• Age > 18 years old and < 75 years old;

• ECOG Performance status score is 0-1;

• Histologically or cytologically confirmed unresectable colorectal adenocarcinoma with liver metastases, with or without extrahepatic metastases;

• At least one measurable lesion as defined by RECIST version 1.1;

• Prior systemic therapy line =2 (treatment of RAS mutations) or =3 (treatment of RAS wild type), and the history of prior therapy must include: fluorouracil, irinotecan, oxaliplatin, anti-VEGF drugs and anti-EGFR drugs (if RAS wild type);

• Known RAS and BRAF status;

• Only patients with normal mismatch repair (pMMR)/microsatellite stability (MSS);

• For the evaluation of PD-L1 tissues and plasma before treatment;

• Child-Pugh grade A: SB < 34mmol/L, ALT < 150U/L, albumin > 35 g/L;

• Hematologic function: white cell count (WBC) > 2.5 x 109/L, platelets =60 x109/L, prothrombin time (PT) prolongation <2s;

• 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.

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 receivedinterventional therapy, ablation or radiotherapy for liver metastases within the past 3 months;

• 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.

Related Conditions & MeSH terms

• CRC

Intervention

Drug:
• Candonilimab (AK104)
Cadonilimab (AK104): 6mg/kg, i.v. q2w.
• Regorafenib
Regorafenib: 80 mg p.o. qd for 3 weeks of every 4 week cycle (i.e. 3 weeks on, 1 week off).

Locations

Country	Name	City	State
China	Huashan Hospital	Shanghai
China	Shanghai Tenth People's Hospital	Shanghai
China	The First Affiliated Hospital of Soochow University	Suzhou	Jiangsu

Sponsors (1)

Lead Sponsor	Collaborator
Jin-hong Chen

Country where clinical trial is conducted

China, 

References & Publications (10)

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Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective Response Rate (ORR)	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	Disease Control Rate (DCR)	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
Secondary	Duration of response (DoR)	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
Secondary	Progression-free Survival (PFS)	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
Secondary	Overall survival (OS)	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
Secondary	Adverse event incidence rate (AE rate)	Safety variables will be summarized using descriptive statistics based on adverse events collection.	6 months