Resectable Colon Cancer, MSI-H/dMMR Colorectal Cancer
Conditions
Brief summary
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 conlon cancer.
Interventions
Anti-PD-1/CTLA-4 tetrameric bispecific antibody
DRUGOxaliplatin
Intravenous
DRUGCapecitabine
Oral
DRUG5- Fluorouracil
Intravenous
DRUGCalcium Folinate
Intravenous
Sponsors
Akeso
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pathologic Complete Response (pCR) rate as assessed by investigator | 1 month after surgery | Proportion of participants with post-surgery stage of ypT0N0 as assessed by investigator |
| Event Free Survival (EFS) | Up to approximately 5 years | Time from randomization to disease progression, local or distant recurrence in post-surgery phase, or death due to any cause |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | Up to approximately 5 years | Time from randomization to death from any cause |
| R0 resection rate | Up to approximately 2 years | Proportion of R0 resection in participant receiving tumor surgery |
| Adverse event | Up to approximately 5 years | Incidence and severity of adverse events (AEs) and clinically significant abnormal laboratory findings |
| Pharmacokinetics (PK) | Up to approximately 2 years | Serum concentrations of AK104 (Cadonilimab) at different point of time after AK104 administration |
| Anti-Drug Antibodies(ADAs) | Up to approximately 2 years | Number and proportion of participants with detectable ADA. |
Countries
China
Contacts
CONTACTXufang Yu, MD
PRINCIPAL_INVESTIGATORRuihua Xu, PhD
Sun Yat-sen University
Outcome results
None listed