Colorectal Cancer Stage IVPhase 1/2NCT05426005
Cadonilimab for PD-1/PD-L1 Blockade-refractory, MSI-H/dMMR, Advanced Colorectal Cancer
A Phase 1/2 study testing Cadonilimab in people with Colorectal Cancer Stage IV and Mismatch Repair-deficient (dMMR), run by Sun Yat-sen University at 1 site in China.
Trial summary
KEYNOTE-177 is currently the only randomized controlled phase III clinical trial evaluating the efficacy and safety of pembrolizumab versus standard chemotherapy combined with targeted first-line therapy for dMMR/MSI-H metastatic colorectal cancer. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colorectal Cancer Stage IV, Mismatch Repair-deficient (dMMR), Microsatellite Instability-high (MSI-H)
- What is being tested?
- Cadonilimab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 28 participants
- Where
- 1 siteChina
- Study dates
- 7 Feb 2023to 1 Dec 2028
- Phase
- Phase 1/2
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Willing and able to provide written informed consent.
- Histological or cytological documentation of adenocarcinoma of the colon or rectum.
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
- Tumor tissues were identified as mismatch repair-deficient (dMMR) by immunohistochemistry (IHC) method or microsatellite instability-high (MSI-H) by polymerase chain reaction (PCR).
- Subjects with stage IV colorectal cancer must have measurable or non measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria, version 1.1.
- Previous treatment with an anti-PD-1 or PD-L1 monoclonal antibody for advanced or metastatic colorectal cancer has failed. Treatment failure was defined as: disease progression or unacceptable toxicity during treatment or within 6 months after the last treatment.
- Adequate bone marrow, liver and renal function as assessed by the laboratory required by protocol.
Who cannot join
- Previously received anti-cytotoxic T lymphocyte-associated antigen 4 (cytotoxic T-lymphocyte-associated Protein 4, CTLA-4) antibody.
- Significant cardiovascular disease including unstable angina or myocardial infarction within 6 months before initiating study treatment.
- Heart failure grade III/IV (NYHA-classification).
- Unresolved toxicity higher than CTCAE v.5.0 Grade 1 attributed to any prior therapy/procedure.
- Subjects with known allergy to the study drugs or to any of its excipients.
- Current or recent (within 4 weeks prior to starting study treatment) treatment of another investigational drug or participation in another investigational study.
- Breast- feeding or pregnant women.
- Lack of effective contraception.
Trial locations and contacts
1 site in 1 country.
China1 site
The Sixth Affiliated Hospital of Sun Yat-sen University
Guangzhou, Guangdong, 510655
About this study
Official title: Cadonilimab (Bispecific Anti-PD-1/CTLA-4 Antibody) for PD-1/PD-L1 Blockade-refractory, Microsatellite Instability-high (MSI-H) or Mismatch Repair-deficient (dMMR), Advanced Colorectal Cancer: a Single Group, Multicenter, Phase 2 Trial
KEYNOTE-177 is currently the only randomized controlled phase III clinical trial evaluating the efficacy and safety of pembrolizumab versus standard chemotherapy combined with targeted first-line therapy for dMMR/MSI-H metastatic colorectal cancer. The study was conducted at 192 centers in 23 countries and enrolled a total of 307 subjects. The results of the study showed that the median PFS of pembrolizumab was 16.5 months, which was double the 8.2 months in the chemotherapy group (HR 0.60; 95% CI: 0.45-0.80; P = 0.0002). In addition, the ORR was 45.1% in the pembrolizumab group and 33.1% in the chemotherapy group, and a higher percentage of patients achieving a complete remission (CR) with pembrolizumab than in the chemotherapy group (13.1% vs. 3.9%). The U.S. FDA approved pembrolizumab in June 2020 for the first-line treatment of MSI-H/dMMR metastatic colorectal cancer.
The results of the KEYNOTE-177 study showed that 29% of patients with dMMR/MSI-H metastatic colorectal cancer experienced direct disease progression (PD) after first-line pembrolizumab monotherapy. This may suggest that some dMMR/MSI-H patients have primary resistance to anti-PD-1 monotherapy. In the first-line treatment cohort of the CheckMate 142 study using nivolumab combined with ipilimumab, the proportion of patients with direct PD was 13%, suggesting that the combination of PD-1 inhibitors and anti-CTLA-4 mAb may have help overcome this primary resistance. In addition, in the second-line and above cohort of the CheckMate142 study, 12% of patients receiving nivolumab in combination with ipilimumab experienced PD directly, compared with 26% of patients receiving nivolumab alone.
Read more
A study published on 《The Lancet Oncolog》 on the efficacy and safety of ipilimumab monotherapy and ipilimumab combined with anti-PD-1 monoclonal antibody in patients with anti-PD-1 monoclonal antibody-resistant melanoma Retrospective study. The study included 355 patients with unresectable metastatic stage III or IV melanoma who received ipilimumab monotherapy after failure of anti-PD-(L)1 monoclonal antibody (n=162), or Ipilimumab combined with anti-PD-1 therapy (n=193). The ORR was 31% in the combination arm, significantly higher than the 13% in the ipilimumab monotherapy arm. In addition, the median OS and PFS of the combination therapy group were 20.4 months and 3.0 months, respectively, which were also significantly higher than those of the single-agent group of 8.8 months and 2.6 months.
The aim of this study was to evaluate the objective response rate (ORR) of Cadonilimab, a bispecific anti-PD-1/CTLA-4 antibody, for PD-1/PD-L1 blockade-refractory, microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR), advanced colorectal cancer.
- Conditions
- Colorectal Cancer Stage IV, Mismatch Repair-deficient (dMMR), Microsatellite Instability-high (MSI-H)
- Being tested
- Cadonilimab
- Keywords
- PD-1, CTLA-4, Immunotherapy
- Medical subject headings
- Colorectal Neoplasms, Turcot syndrome, Diabetes Mellitus, Insulin-Dependent, 12
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CadonilimabDrug
Cadonilimab, 6 mg/kg every 2 weeks until disease progression, intolerable toxicity, or duration of treatment for 2 years
| Study group | Role | What they receive |
|---|---|---|
| Cadonilimab | Experimental | Cadonilimab alone Receives: Drug: Cadonilimab |
What is being measured
The primary outcome is the main question the study is designed to answer.
12-month Progression-free survival (PFS) rate
The PFS was defined as the time from enrollment until tumor progression or death from any cause, whichever occurred first. The 12-month PFS rate was defined as the proportion of patients without disease progression or death at the 12th month after initiation of the study. treatment.
Measured: 2 years
Secondary outcomes (3)
Objective response rate (ORR)
The percentage of subjects with total number of Complete Response (CR) + total number of Partial Response (PR).
Measured: 2 years
Overall Survival (OS)
OS is defined as the time from date of randomization to death due to any cause. Subjects still alive at the time of analysis were censored at their last date of last contact.
Measured: 5 years
Toxicity assessed using the The National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 5.0.
The grade of toxicity will be assessed using the NCI-CTCAE, version 5.0. Grade refers to the severity of the AE. The CTCAE displays Grades 1 (lowest level) through 5 (highest level) with unique clinical descriptions of severity.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jun 2022
- Study start7 Feb 2023
- Primary completion1 Sep 2026 (estimated)
- Study completion1 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Colorectal Cancer Stage IVStudies of the same condition, open and under way.
- More trials run by Sun Yat-sen 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 28 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sun Yat-sen University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Yanhong Deng, Sun Yat-sen University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05426005
- Sponsor's protocol ID
- CSWOG-C03
- Status last verified
- Jun 2026
- First submitted
- 15 Jun 2022
- Last updated
- 24 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cadonilimab (Bispecific Anti-PD-1/CTLA-4 Antibody) for PD-1/PD-L1 Blockade-refractory, Microsatellite Instability-high (MSI-H) or Mismatch Repair-deficient (dMMR), Advanced Colorectal Cancer: a Single Group, Multicenter, Phase 2 Trial
- ClinicalTrials.gov ID
- NCT05426005
- Acronym / sponsor ID
- CSWOG-C03
- Conditions
- Colorectal Cancer Stage IV, Mismatch Repair-deficient (dMMR), Microsatellite Instability-high (MSI-H)
- Keywords
- PD-1, CTLA-4, Immunotherapy
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 28 participants (estimated)
- Lead sponsor
- Sun Yat-sen UniversityUniversity, hospital or other
- Study start
- 7 Feb 2023 (actual)
- Primary completion
- 1 Sep 2026 (estimated)
- Study completion
- 1 Dec 2028 (estimated)
- First posted
- 21 Jun 2022 (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.
KEYNOTE-177 is currently the only randomized controlled phase III clinical trial evaluating the efficacy and safety of pembrolizumab versus standard chemotherapy combined with targeted first-line therapy for dMMR/MSI-H metastatic colorectal cancer. The study was conducted at 192 centers in 23 countries and enrolled a total of 307 subjects. The results of the study showed that the median PFS of pembrolizumab was 16.5 months, which was double the 8.2 months in the chemotherapy group (HR 0.60; 95% CI: 0.45-0.80; P = 0.0002). In addition, the ORR was 45.1% in the pembrolizumab group and 33.1% in the chemotherapy group, and a higher percentage of patients achieving a complete remission (CR) with pembrolizumab than in the chemotherapy group (13.1% vs. 3.9%). The U.S. FDA approved pembrolizumab in June 2020 for the first-line treatment of MSI-H/dMMR metastatic colorectal cancer.
The results of the KEYNOTE-177 study showed that 29% of patients with dMMR/MSI-H metastatic colorectal cancer experienced direct disease progression (PD) after first-line pembrolizumab monotherapy. This may suggest that some dMMR/MSI-H patients have primary resistance to anti-PD-1 monotherapy. In the first-line treatment cohort of the CheckMate 142 study using nivolumab combined with ipilimumab, the proportion of patients with direct PD was 13%, suggesting that the combination of PD-1 inhibitors and anti-CTLA-4 mAb may have help overcome this primary resistance. In addition, in the second-line and above cohort of the CheckMate142 study, 12% of patients receiving nivolumab in combination with ipilimumab experienced PD directly, compared with 26% of patients receiving nivolumab alone.
A study published on 《The Lancet Oncolog》 on the efficacy and safety of ipilimumab monotherapy and ipilimumab combined with anti-PD-1 monoclonal antibody in patients with anti-PD-1 monoclonal antibody-resistant melanoma Retrospective study. The study included 355 patients with unresectable metastatic stage III or IV melanoma who received ipilimumab monotherapy after failure of anti-PD-(L)1 monoclonal antibody (n=162), or Ipilimumab combined with anti-PD-1 therapy (n=193). The ORR was 31% in the combination arm, significantly higher than the 13% in the ipilimumab monotherapy arm. In addition, the median OS and PFS of the combination therapy group were 20.4 months and 3.0 months, respectively, which were also significantly higher than those of the single-agent group of 8.8 months and 2.6 months.
The aim of this study was to evaluate the objective response rate (ORR) of Cadonilimab, a bispecific anti-PD-1/CTLA-4 antibody, for PD-1/PD-L1 blockade-refractory, microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR), advanced colorectal cancer.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Cadonilimab | Experimental | Drug: CadonilimabCadonilimab alone |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Willing and able to provide written informed consent.
- Histological or cytological documentation of adenocarcinoma of the colon or rectum.
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
- Tumor tissues were identified as mismatch repair-deficient (dMMR) by immunohistochemistry (IHC) method or microsatellite instability-high (MSI-H) by polymerase chain reaction (PCR).
- Subjects with stage IV colorectal cancer must have measurable or non measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria, version 1.1.
Key exclusion criteria (8 listed)
- Previously received anti-cytotoxic T lymphocyte-associated antigen 4 (cytotoxic T-lymphocyte-associated Protein 4, CTLA-4) antibody.
- Significant cardiovascular disease including unstable angina or myocardial infarction within 6 months before initiating study treatment.
- Heart failure grade III/IV (NYHA-classification).
- Unresolved toxicity higher than CTCAE v.5.0 Grade 1 attributed to any prior therapy/procedure.
- Subjects with known allergy to the study drugs or to any of its excipients.
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 |
|---|---|---|
| CadonilimabCadonilimab, 6 mg/kg every 2 weeks until disease progression, intolerable toxicity, or duration of treatment for 2 years | Drug | Cadonilimab |
Primary outcome
12-month Progression-free survival (PFS) rate
Time frame: 2 years
The PFS was defined as the time from enrollment until tumor progression or death from any cause, whichever occurred first. The 12-month PFS rate was defined as the proportion of patients without disease progression or death at the 12th month after initiation of the study. treatment.
3 secondary outcomes
Objective response rate (ORR)
Time frame: 2 years
Overall Survival (OS)
Time frame: 5 years
Toxicity assessed using the The National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 5.0.
Time frame: 2 years
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 24 Jun 2026.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Cadonilimab in people with Colorectal Cancer Stage IV and Mismatch Repair-deficient (dMMR), run by Sun Yat-sen 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 7 inclusion and 8 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 24 Jun 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
12-month Progression-free survival (PFS) rate (time frame: 2 years). 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 24 Jun 2026.