Neoadjuvant/Adjuvant AK104 in Microsatellite Instability-high or Mismatch Repair-deficient, Resectable Colon Cancer

A Randomized, Open-label, Controlled, Multicenter Phase 3 Clinical Trial of AK104 for Neoadjuvant/Adjuvant Treatment of Microsatellite Instability-high or Mismatch Repair-deficient, Resectable Colon Cancer

This is a randomized, open-label, controlled, multicenter phase 3 study. All patients are resectable microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) colon cancer. The purpose of this study is to evaluate the efficacy and safety of neoadjuvant/adjuvant treatment of AK104 (Cadonilimab) versus adjuvant chemotherapy in patients with resectable MSI-H/dMMR colon cancer.

Study Overview

• Status: Recruiting
• Conditions: Resectable Colon Cancer; MSI-H/dMMR Colorectal Cancer
• Intervention / Treatment: Drug: Capecitabine; Drug: Cadonilimab (AK104); Drug: Oxaliplatin; Drug: 5- Fluorouracil; Drug: Calcium Folinate

• Study Type: Interventional
• Enrollment (Estimated): 386
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Xufang Yu, MD; Phone Number: 021-60472800; Email: xufang.yu@akesobio.com

Study Locations

• China
  • Guangzhou, China
    • Recruiting
    • Sun Yat-sen University Cancer Center
    • Contact: Ruihua Xu, PhD; Phone Number: 020-87343468; Email: xurh@sysucc.org.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Voluntarily sign a written ICF.
2. ≥ 18, ≤ 75 years old at the time of enrollment, regardless of sex.
3. Eastern Cooperative Oncology Organization (ECOG) performance status score of 0 or 1.
4. Life expectancy greater than 2 years.
5. Histologically confirmed primary colon adenocarcinoma (without squamous carcinoma or sarcomatoid components); colon is defined as ≥ 12cm from the anal verge by colonscopy.
6. Participants with resectable stage IIB-III colon cancer according to the AJCC 8th staging, as assessed by imaging (enhanced CT or enhanced MRI) .
7. Microsatellite instability detection demostrates MSI-H (with 5 NCI-recommended microsatellite detection sites: BAT25, BAT26, D5S346, D2S123, D17S250, or combinations of other guidelines and clinically recognized site) , or mismatch repair detection demostrates dMMR (evaluating the expression of 4 MMR proteins: MLH1, MSH2, MSH6, PMS2 by immunohistochemistry, and positive expression is localized to the nucleus).
8. Before enrollment, the participant needs to be evaluated by the responsible surgeon to confirm whether he/she is eligible for radical R0 resection, and does not require combined organ resection based on medical history.
9. Female participants of childbearing potential must have a urine or serum pregnancy test within 3 days before the first dose (if the urine pregnancy test result cannot be confirmed as negative, a serum pregnancy test is required, and the serum pregnancy result shall prevail), and the result is negative. If a female participant of childbearing potential has sex with a male partner who is not sterilized, the participant must use an acceptable method of contraception from screening and must agree to use a contraceptive method continuously until 120 days after the last dose of study drug; Contraception should be discussed with the investigator as to whether to discontinue contraception after this time point.
10. If a non-sterilized male participant has sex with a female partner of childbearing potential, the participant must take an effective method of contraception from the beginning of screening until 120 days after the last dose; Contraception should be discussed with the investigator as to whether to discontinue contraception after this time point.

Exclusion Criteria:

1. Previously received any anti-tumor treatment for the study disease, including surgery, radiotherapy, chemotherapy, targeted therapy, immunotherapy, etc.
2. Previously (within 3 years) or currently suffering from other malignant tumors, except for cured local tumors (such as basal cell carcinoma, squamous cell carcinoma of the skin, superficial bladder cancer, cervical carcinoma in situ, etc.).
3. Participated in treatment with investigation drugs or used investigation devices within 4 weeks prior to randomization.
4. History of immunodeficiency; tested positive for HIV antibodies; currently on long-term systemic corticosteroids or other immunosuppressive agents.
5. Known active tuberculosis (TB); subjects suspected of having active TB need clinical examination for exclusion; known active syphilis infection.
6. Known history of allograft organ transplantation or allograft hematopoietic stem cell transplantation.
7. Previous history of pneumonitis/interstitial lung disease requiring systemic corticosteroid treatment or currently having pneumonitis.
8. Experiencing severe infection within 4 weeks prior to randomization, including but not limited to complications requiring hospitalization, sepsis, or severe pneumonia; having received systemic anti-infection treatment for active infection within 2 weeks prior to randomization (excluding antiviral therapy for hepatitis B or hepatitis C).
9. Subjects with active hepatitis B (HBsAg positive and HBV-DNA over 1000 copies/ml (200 IU/ml) or above the lower limit of detection, whichever is higher). Note: Subjects with hepatitis B are required to receive antiviral treatment throughout the study.
10. Pregnant or breastfeeding women.
11. Previously or currently having any disease, treatment, or abnormal laboratory test results that could confound study results, affect full participation in the study, or make participation not in the best interest of the participant.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AK104; Participants will receive AK104 before and after surgery	Drug: Cadonilimab (AK104); Anti-PD-1/CTLA-4 tetrameric bispecific antibody
Active Comparator: Physician's choice of chemotherapy; Participants will receive physician's choice of chemotherapy after surgery	Drug: Capecitabine; Oral; Drug: Oxaliplatin; Intravenous; Drug: 5- Fluorouracil; Intravenous; Drug: Calcium Folinate; Intravenous

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathologic Complete Response (pCR) rate as assessed by investigator	Proportion of participants with post-surgery stage of ypT0N0 as assessed by investigator	1 month after surgery
Event Free Survival (EFS)	Time from randomization to disease progression, local or distant recurrence in post-surgery phase, or death due to any cause	Up to approximately 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	Time from randomization to death from any cause	Up to approximately 5 years
R0 resection rate	Proportion of R0 resection in participant receiving tumor surgery	Up to approximately 2 years
Pharmacokinetics (PK)	Serum concentrations of AK104 (Cadonilimab) at different point of time after AK104 administration	Up to approximately 2 years
Anti-Drug Antibodies(ADAs)	Number and proportion of participants with detectable ADA.	Up to approximately 2 years
Adverse event	Incidence and severity of adverse events (AEs) and clinically significant abnormal laboratory findings	Up to approximately 5 years

Collaborators and Investigators

• Sponsor: Akeso
• Investigators: Principal Investigator: Ruihua Xu, PhD, Sun Yat-sen University Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): April 15, 2026
• Primary Completion (Estimated): June 15, 2030
• Study Completion (Estimated): March 15, 2031

Study Registration Dates

• First Submitted: February 9, 2026
• First Submitted That Met QC Criteria: February 9, 2026
• First Posted (Actual): February 17, 2026

Study Record Updates

• Last Update Posted (Actual): April 22, 2026
• Last Update Submitted That Met QC Criteria: April 20, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Nucleic Acids, Nucleotides, and Nucleosides; Enzymes and Coenzymes; Coordination Complexes; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Nucleosides; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Uracil; Pyrimidinones; Coenzymes; Deoxyribonucleosides; Capecitabine; Oxaliplatin; Fluorouracil; Leucovorin
• Other Study ID Numbers: AK104-313

Drug and device information, study documents

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