Neoadjuvant and adjuvant AK104 for resectable MSI-H/dMMR 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 phase 3 trial will test whether giving the antibody AK104 before and after surgery works better than standard adjuvant chemotherapy for adults with resectable MSI‑H or dMMR colon cancer.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 386 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Akeso (Industry-sponsored)
• Drugs / interventions: chemotherapy, immunotherapy, Cadonilimab
• Locations: 1 site (Guangzhou)
• Trial ID: NCT07412613 on ClinicalTrials.gov

What this trial studies

This randomized, open‑label, controlled phase 3 trial enrolls adults with resectable stage IIB‑III colon adenocarcinoma that is MSI‑H or dMMR. Participants are randomly assigned to receive neoadjuvant and adjuvant AK104 (cadonilimab) or to undergo standard surgery followed by adjuvant chemotherapy (oxaliplatin and fluoropyrimidine‑based regimens). The study will compare efficacy and safety outcomes, including recurrence and survival endpoints, as well as surgical and pathological responses. Treatments and follow‑up are delivered at participating clinical centers with regular imaging and clinical assessments.

Who should consider this trial

Good fit: Adults age 18–75 with histologically confirmed resectable stage IIB–III colon adenocarcinoma, ECOG 0–1, and laboratory confirmation of MSI‑H or dMMR are the intended candidates.

Not a fit: Patients with non‑MSI‑H/dMMR tumors, unresectable disease, poor performance status, or who cannot undergo planned surgery are unlikely to benefit from this trial.

Why it matters

Potential benefit: If successful, the approach could lower recurrence and improve cure rates compared with standard adjuvant chemotherapy for patients with resectable MSI‑H/dMMR colon cancer.

How similar studies have performed: Immune checkpoint inhibitors have shown strong activity in advanced MSI‑H/dMMR colorectal cancers and promising signals in small neoadjuvant series, but using AK104 in a randomized neoadjuvant/adjuvant phase 3 setting is a newer, confirmatory approach.

Eligibility criteria

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.

Where this trial is running

Guangzhou

• Sun Yat-sen University Cancer Center — Guangzhou, China (Recruiting)

Study contacts

• Principal investigator: Ruihua Xu, PhD — Sun Yat-Sen University Cancer Center
• Study coordinator: Xufang Yu, MD

Conditions Resectable Colon Cancer; MSI-H/dMMR Colorectal Cancer