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

Official title

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

Overview

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.

Interventions

• Drug Cadonilimab (AK104)
  Anti-PD-1/CTLA-4 tetrameric bispecific antibody
• Drug Oxaliplatin
  Intravenous
• Drug Capecitabine
  Oral
• Drug 5- Fluorouracil
  Intravenous
• Drug Calcium Folinate
  Intravenous

Primary outcome measures

• Pathologic Complete Response (pCR) rate as assessed by investigator [Time frame: 1 month after surgery]
• Event Free Survival (EFS) [Time frame: Up to approximately 5 years]

Secondary outcome measures (5)

• Overall Survival (OS) [Time frame: Up to approximately 5 years]
• R0 resection rate [Time frame: Up to approximately 2 years]
• Adverse event [Time frame: Up to approximately 5 years]
• Pharmacokinetics (PK) [Time frame: Up to approximately 2 years]
• Anti-Drug Antibodies(ADAs) [Time frame: Up to approximately 2 years]

Eligibility criteria

Inclusion criteria

• Voluntarily sign a written ICF.
• ≥ 18, ≤ 75 years old at the time of enrollment, regardless of sex.
• Eastern Cooperative Oncology Organization (ECOG) performance status score of 0 or 1.
• Life expectancy greater than 2 years.
• Histologically confirmed primary colon adenocarcinoma (without squamous carcinoma or sarcomatoid components); colon is defined as ≥ 12cm from the anal verge by colonscopy.
• Participants with resectable stage IIB-III colon cancer according to the AJCC 8th staging, as assessed by imaging (enhanced CT or enhanced MRI) .
• 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).
• 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.
• 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.
• 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

• Previously received any anti-tumor treatment for the study disease, including surgery, radiotherapy, chemotherapy, targeted therapy, immunotherapy, etc.
• 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.).
• Participated in treatment with investigation drugs or used investigation devices within 4 weeks prior to randomization.
• History of immunodeficiency; tested positive for HIV antibodies; currently on long-term systemic corticosteroids or other immunosuppressive agents.
• Known active tuberculosis (TB); subjects suspected of having active TB need clinical examination for exclusion; known active syphilis infection.
• Known history of allograft organ transplantation or allograft hematopoietic stem cell transplantation.
• Previous history of pneumonitis/interstitial lung disease requiring systemic corticosteroid treatment or currently having pneumonitis.
• 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).
• 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.
• Pregnant or breastfeeding women.
• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Sun Yat-sen University Cancer Center — Guangzhou

Identifiers

NCT: NCT07412613 · AK104-313

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗