MSI-H/dMMR Gastric Carcinoma and Colorectal CancerPhase 2NCT04556253
Perioperative Cadonilimab (AK104) in Locally Advanced MSI-H/dMMR Gastric or Gastroesophageal Junction and Colorectal Adenocarcinoma
A Phase 2 study testing AK104 and Radical Surgery in people with MSI-H/dMMR Gastric Carcinoma and Colorectal Cancer, run by Peking University at 1 site in China.
Trial summary
The goal of this phase 2 clinical trial is to learn whether a medicine called cadonilimab (AK104) can safely and effectively treat certain stomach and colon cancers when it is given before and after surgery. Cadonilimab is a type of immunotherapy that targets PD-1 and CTLA-4. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- MSI-H/dMMR Gastric Carcinoma and Colorectal Cancer
- What is being tested?
- AK104 and Radical Surgery
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 47 participants
- Where
- 1 siteChina
- Study dates
- 1 Feb 2024to Dec 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Written and signed informed consent.
- Eastern Cooperative Oncology Group (ECOG) Performance Score of 0 or 1.
- The estimated life expectancy of ≥3 months.
- Confirmed MSI-H/dMMR status by the central laboratory.
- For cohort 1, histologically or cytologically documented locally advanced gastric carcinoma(cT3-T4a, Nx, M0). For cohort 2, histologically or cytologically documented locally advanced colorectal cancer(cT3-T4a, Nx, M0).
- Haven't received any chemotherapy or radiotherapy.
- Adequate organ function.
- All female and male subjects of reproductive potential must agree to use an effective method of contraception, as determined by the Investigator, during and for 120 days after the last dose of study treatment.
Who cannot join
- Is currently participating in a study of an investigational agent or using an investigational device;
- Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy within 2 years prior to the first dose of study treatment;
- Has undergone major surgery within 30 days of Study Day 1;
- Has a known additional malignancy that is progressing or requires systemic treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
- Has known active central nervous system (CNS) metastases;
- Has carcinomatous meningitis;
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- Has an active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment NOTE: Subjects with vitiligo or resolved childhood asthma/atopy would be an exception to this rule. Subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study;
- Has an active infection requiring systemic therapy;
- Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected);
- History of myocardial infarction, unstable angina, cardiac or other vascular stenting, angioplasty, or surgery within 12 months prior to day 1 of study treatment;
- Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of this subject to participate, in the opinion of the treating investigator;
- Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study;
- Has received a live virus vaccine within 30 days of the planned first dose of study therapy;
- Is pregnant, breastfeeding, or expecting to conceive or father a child within the projected duration of the study including 120 days following the last dose of study treatment;
- Has any concurrent medical condition that, in the opinion of the Investigator, would complicate or compromise compliance with the study or the well-being of the subject.
Trial locations and contacts
1 site in 1 country.
China1 site
Peking University Cancer Hospital & Institute
Beijing, Beijing Municipality, 100142
About this study
Official title: A Multicenter, Open-Label, Phase II Study of Anti-PD-1/CTLA-4 Bispecific Antibody AK104 in the Perioperative Treatment of Locally Advanced Microsatellite Instability/Mismatch Repair Protein-Deficient Gastric and Colorectal Adenocarcinoma
The goal of this phase 2 clinical trial is to learn whether a medicine called cadonilimab (AK104) can safely and effectively treat certain stomach and colon cancers when it is given before and after surgery. Cadonilimab is a type of immunotherapy that targets PD-1 and CTLA-4. The study includes two groups of participants:
- Cohort 1: people with locally advanced gastric or gastroesophageal junction adenocarcinoma
- Cohort 2: people with locally advanced colorectal adenocarcinoma
Read more
All participants will have a tumor with a genetic change called MSI-H or dMMR and will be able to have surgery.The main question this study aims to answer is:• How many participants have no signs of cancer left in the tissue removed during surgery (pathologic complete response) after receiving cadonilimab?Other questions the study will look at include:
- How long participants live overall and without the cancer coming back
- How many participants have a major but not complete response in the removed tumor tissue
- What side effects happen with cadonilimab before and after surgery
In this multicenter, single-arm trial, all participants will:
- Receive cadonilimab by intravenous infusion every 3 weeks for 3 cycles before surgery
- Have surgery to remove the tumor
- May continue cadonilimab once a month for up to 6 months after surgery, or stop sooner if the cancer gets worse or side effects are not tolerable
- Have regular clinic visits, blood tests, and scans so researchers can monitor their health and how the cancer responds to treatment
The study uses a two-stage design to decide whether cadonilimab shows enough benefit to justify further research.
- Being tested
- AK104, Radical Surgery
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AK104Drug
Participants will receive AK104 10 mg/kg by intravenous infusion every 3 weeks for 3 cycles before surgery. Surgery will be performed 3-6 weeks after completion of neoadjuvant treatment. After surgery, participants will receive AK104 6 mg/kg by intravenous infusion once monthly for up to 6 months or until disease progression, unacceptable toxicity, withdrawal of consent, or other protocol-defined discontinuation criteria are met.
Radical SurgeryProcedure or surgery
For participants with gastric or gastroesophageal junction adenocarcinoma, radical gastrectomy or gastroesophageal junction resection with appropriate lymphadenectomy will be performed according to tumor location and institutional standards. For participants with colorectal adenocarcinoma, radical colorectal resection with regional lymphadenectomy, will be performed according to tumor location and institutional standards.
| Study group | Role | What they receive |
|---|---|---|
| AK104 for Gastric/GEJ and Colorectal Adenocarcinoma | Experimental | Participants with locally advanced MSI-H or dMMR gastric/GEJ and colorectal adenocarcinoma will receive neoadjuvant AK104 10 mg/kg by intravenous infusion every 3 weeks for 3 cycles. Surgery will be performed 3-6 weeks after completion of neoadjuvant treatment. After surgery, participants will receive postoperative AK104 6 mg/kg by intravenous infusion once monthly for up to 6 months or until disease progression, unacceptable toxicity, withdrawal of consent, or other discontinuation criteria are met. Receives: Drug: AK104; Procedure: Radical Surgery |
What is being measured
The primary outcome is the main question the study is designed to answer.
The rate of pathologic complete response
Proportion of patients with locally advanced dMMR/MSI-H gastric or colorectal adenocarcinoma who receive neoadjuvant AK104 monotherapy and undergo surgery, who achieve a pathologic complete response based on blinded pathologic assessment by two pathologists with an associate senior professional title or higher.
Measured: After surgery, 3-6 weeks after the last neoadjuvant AK104 dose (up to 3 cycles; each cycle is 21 days).
Secondary outcomes (8)
Major Pathologic Response (MPR) rate
Proportion of participants who achieve a major pathologic response, defined as residual viable tumor (RVT) ≤10% in the resected primary tumor specimen.
Measured: After surgery, 3-6 weeks after the last neoadjuvant AK104 dose (up to 3 cycles; each cycle is 21 days).
R0 resection rate
Proportion of participants who achieve an R0 resection, defined as microscopically margin-negative resection with no residual tumor at the resection margins.
Measured: At surgery, 3-6 weeks after the last neoadjuvant AK104 dose (up to 3 cycles; each cycle is 21 days).
Event-free survival (EFS)
Measured: From the first dose of study treatment to the first EFS event or censoring, up to 5 years; EFS rates assessed at 12, 24, and 36 months.
Disease-Free Survival (DFS)
Measured: From the first dose of study treatment to the first DFS event or censoring, up to 5 years; DFS rates assessed at 12, 24, and 36 months.
Overall survival (OS)
Measured: From the first dose of study treatment to the first OS event or censoring, up to 5 years; OS rates assessed at 12, 24, and 36 months.
Postoperative Complication Within 30 Days
Measured: From the date of surgery through 30 days after surgery.
Adverse Events (AEs)
Measured: From first dose to 30 days after the last study-treatment dose or start of other anticancer therapy, whichever occurs first; immune-related AEs through 90 days after the last AK104 dose, regardless of subsequent anticancer therapy.
Completion Rate of Postoperative Adjuvant Therapy
Measured: From the first postoperative adjuvant dose to completion or discontinuation of the 6 planned cycles (each cycle is 28 days; planned duration is 24 weeks).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Sep 2020
- Study start1 Feb 2024
- Primary completionDec 2026 (estimated)
- Study completionDec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for MSI-H/dMMR Gastric Carcinoma and Colorectal CancerStudies of the same condition, open and under way.
- More trials run by Peking UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 47 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Peking University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jiafu Ji, Peking University Cancer Hospital & Institute
- Investigators
- Jiafu Ji, Principal investigator, Peking University Cancer Hospital & Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04556253
- Sponsor's protocol ID
- AK104-IIT-002
- Status last verified
- Jun 2026
- First submitted
- 14 Sep 2020
- Last updated
- 5 Nov 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Open-Label, Phase II Study of Anti-PD-1/CTLA-4 Bispecific Antibody AK104 in the Perioperative Treatment of Locally Advanced Microsatellite Instability/Mismatch Repair Protein-Deficient Gastric and Colorectal Adenocarcinoma
- ClinicalTrials.gov ID
- NCT04556253
- Acronym / sponsor ID
- AK104-IIT-002
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 47 participants (estimated)
- Lead sponsor
- Peking UniversityUniversity, hospital or other
- Study start
- 1 Feb 2024 (actual)
- Primary completion
- Dec 2026 (estimated)
- Study completion
- Dec 2028 (estimated)
- First posted
- 21 Sep 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this phase 2 clinical trial is to learn whether a medicine called cadonilimab (AK104) can safely and effectively treat certain stomach and colon cancers when it is given before and after surgery. Cadonilimab is a type of immunotherapy that targets PD-1 and CTLA-4. The study includes two groups of participants:
- Cohort 1: people with locally advanced gastric or gastroesophageal junction adenocarcinoma
- Cohort 2: people with locally advanced colorectal adenocarcinoma
All participants will have a tumor with a genetic change called MSI-H or dMMR and will be able to have surgery.The main question this study aims to answer is:• How many participants have no signs of cancer left in the tissue removed during surgery (pathologic complete response) after receiving cadonilimab?Other questions the study will look at include:
- How long participants live overall and without the cancer coming back
- How many participants have a major but not complete response in the removed tumor tissue
- What side effects happen with cadonilimab before and after surgery
In this multicenter, single-arm trial, all participants will:
- Receive cadonilimab by intravenous infusion every 3 weeks for 3 cycles before surgery
- Have surgery to remove the tumor
- May continue cadonilimab once a month for up to 6 months after surgery, or stop sooner if the cancer gets worse or side effects are not tolerable
- Have regular clinic visits, blood tests, and scans so researchers can monitor their health and how the cancer responds to treatment
The study uses a two-stage design to decide whether cadonilimab shows enough benefit to justify further research.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| AK104 for Gastric/GEJ and Colorectal Adenocarcinoma | Experimental | Drug: AK104, Procedure: Radical SurgeryParticipants with locally advanced MSI-H or dMMR gastric/GEJ and colorectal adenocarcinoma will receive neoadjuvant AK104 10 mg/kg by intravenous infusion every 3 weeks for 3 cycles. Surgery will be performed 3-6 weeks after completion of neoadjuvant treatment. After surgery, participants will receive postoperative AK104 6 mg/kg by intravenous infusion once monthly for up to 6 months or until disease progression, unacceptable toxicity, withdrawal of consent, or other discontinuation criteria are met. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Written and signed informed consent.
- Eastern Cooperative Oncology Group (ECOG) Performance Score of 0 or 1.
- The estimated life expectancy of ≥3 months.
- Confirmed MSI-H/dMMR status by the central laboratory.
- For cohort 1, histologically or cytologically documented locally advanced gastric carcinoma(cT3-T4a, Nx, M0). For cohort 2, histologically or cytologically documented locally advanced colorectal cancer(cT3-T4a, Nx, M0).
Key exclusion criteria (15 listed)
- Is currently participating in a study of an investigational agent or using an investigational device;
- Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy within 2 years prior to the first dose of study treatment;
- Has undergone major surgery within 30 days of Study Day 1;
- Has a known additional malignancy that is progressing or requires systemic treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
- Has known active central nervous system (CNS) metastases;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AK104Participants will receive AK104 10 mg/kg by intravenous infusion every 3 weeks for 3 cycles before surgery. Surgery will be performed 3-6 weeks after completion of neoadjuvant treatment. After surgery, participants will receive AK104 6 mg/kg by intravenous infusion once monthly for up to 6 months or until disease progression, unacceptable toxicity, withdrawal of consent, or other protocol-defined discontinuation criteria are met. | Drug | AK104 for Gastric/GEJ and Colorectal Adenocarcinoma |
| Radical SurgeryFor participants with gastric or gastroesophageal junction adenocarcinoma, radical gastrectomy or gastroesophageal junction resection with appropriate lymphadenectomy will be performed according to tumor location and institutional standards. For participants with colorectal adenocarcinoma, radical colorectal resection with regional lymphadenectomy, will be performed according to tumor location and institutional standards. | Procedure or surgery | AK104 for Gastric/GEJ and Colorectal Adenocarcinoma |
Primary outcome
The rate of pathologic complete response
Time frame: After surgery, 3-6 weeks after the last neoadjuvant AK104 dose (up to 3 cycles; each cycle is 21 days).
Proportion of patients with locally advanced dMMR/MSI-H gastric or colorectal adenocarcinoma who receive neoadjuvant AK104 monotherapy and undergo surgery, who achieve a pathologic complete response based on blinded pathologic assessment by two pathologists with an associate senior professional title or higher.
8 secondary outcomes
Major Pathologic Response (MPR) rate
Time frame: After surgery, 3-6 weeks after the last neoadjuvant AK104 dose (up to 3 cycles; each cycle is 21 days).
R0 resection rate
Time frame: At surgery, 3-6 weeks after the last neoadjuvant AK104 dose (up to 3 cycles; each cycle is 21 days).
Event-free survival (EFS)
Time frame: From the first dose of study treatment to the first EFS event or censoring, up to 5 years; EFS rates assessed at 12, 24, and 36 months.
Disease-Free Survival (DFS)
Time frame: From the first dose of study treatment to the first DFS event or censoring, up to 5 years; DFS rates assessed at 12, 24, and 36 months.
Overall survival (OS)
Time frame: From the first dose of study treatment to the first OS event or censoring, up to 5 years; OS rates assessed at 12, 24, and 36 months.
Postoperative Complication Within 30 Days
Time frame: From the date of surgery through 30 days after surgery.
Adverse Events (AEs)
Time frame: From first dose to 30 days after the last study-treatment dose or start of other anticancer therapy, whichever occurs first; immune-related AEs through 90 days after the last AK104 dose, regardless of subsequent anticancer therapy.
Completion Rate of Postoperative Adjuvant Therapy
Time frame: From the first postoperative adjuvant dose to completion or discontinuation of the 6 planned cycles (each cycle is 28 days; planned duration is 24 weeks).
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Nov 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jiafu Ji principal investigator
Peking University Cancer Hospital & Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing AK104 and Radical Surgery in people with MSI-H/dMMR Gastric Carcinoma and Colorectal Cancer, run by Peking University at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 5 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The rate of pathologic complete response (time frame: After surgery, 3-6 weeks after the last neoadjuvant AK104 dose (up to 3 cycles; each cycle is 21 days).). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Nov 2026; AzTrials last refreshed its copy on 8 Nov 2026.