Colorectal CancerPhase 2MSI-H/dMMRNCT05913570
Cadonilimab as Neoadjuvant Therapy in Resectable Stage II-III MSI-H/dMMR Colorectal Cancer
A Phase 2 study testing Cadonilimab (®), a PD-1/CTLA-4 bi-specific antibody in people with Colorectal Cancer and Mismatch Repair-deficient (dMMR), run by LiuYing at 1 site in China.
Trial summary
This study will evaluate the safety, and tolerability of Cadonilimab as neoadjuvant treatment for resectable local advanced colorectal cancer patient with dMMR/MSI-H. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colorectal Cancer, Mismatch Repair-deficient (dMMR), Microsatellite Instability-high (MSI-H)
- What is being tested?
- Cadonilimab (®), a PD-1/CTLA-4 bi-specific antibody
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 1 siteChina
- Study dates
- 20 Jun 2023to 20 Dec 2023
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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.
- Male or female subjects > 18 years
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Histological or cytological documentation of adenocarcinoma of the colon or rectum; Tumor tissues were identified as mismatch repair-deficient (dMMR) by immunohistochemistry (IHC) method or microsatellite instability-high (MSI-H) by polymerase chain reaction (PCR) in local site; For colon cancer must be determined by CT or MRI scans as locally advanced (T4) or cN1-2 [with the definition of a clinically positive lymph node being any node ≥ 1.0 cm]). Participants should be eligible for radical resection of R0.
- At least one measurable lesion as defined by RECIST 1.1
- Willing and able to provide 2ml blood and archived tumor tissue sample for MSI status testing. Patients who do not have adequate archival tumor tissue available should undergo a fresh tumor biopsy
- Adequate bone marrow, hepatic and renal function as assessed by the following laboratory requirements conducted within 7 days of starting study treatment.
- Willingness of men and women of reproductive potential to observe conventional and effective birth control for the duration of treatment and for 120 days following the last dose of study treatment; this may include barrier methods such as condom or diaphragm with spermicidal gel.
Who cannot join
- Previous any systemic anticancer therapy for colorectal cancer disease, including chemotherapy, radiothapy or immunotherapy
- Previously received anti-programmed death-1 (PD-1) or its ligand (PD-L1) antibody, anti-cytotoxic T lymphocyte-associated antigen 4 (cytotoxic T-lymphocyte-associated Protein 4, CTLA-4) antibody or other drug/antibody that acts on T cell costimulation or checkpoint pathways.
- Subjects with known allergy to monoclonal antibodies
- Previous or concurrent cancer that is distinct in primary site or histology from colon cancer within 2 years prior to study drug treatment.
- Concurrent with active autoimmune disease or Participants with a history of autoimmune disease who may recur
- Subjects receiving immunosuppressive agents (such as steroids, or corticosteroids at physiologic replacement doses, equivalent to ≤ 10 mg prednisone daily ) for any reason within 14 days before the study drug treatment.
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- Uncontrolled hypertension or hyperglycemia within 14 days before the study drug treatment.
- Uncontrolled pleural effusion, pericardial effusion, or ascites requiring frequent drainage (recurrent within 14 days of study drug treatment)
- History of interstitial lung disease, noninfectious pneumonia, or poorly controlled lung disease (including pulmonary fibrosis, acute lung disease).
- Active systemic bacterial, viral, or fungal infection， requiring systemic treatment within 14 days before study drug treatment.
- Positive test for hepatitis B virus surface antigen with HBV DNA> 500 IU/mL（> 2500copies/mL）at screening or untreated Chronic hepatitis B
- Positive test for hepatitis C virus ribonucleic acid (if antihepatitis C virus antibody tested positive) at screening;
- Known history of testing positive for human immunodeficiency virus (HIV)
- Major surgery for any reason, except diagnostic biopsy, within 28 days of the first administration of study drug. The subject must fully recovered from prior treatment before the first administration of study drug
- Previous allogeneic stem cell transplantation or organ transplantation
- Previous history of myocarditis, cardiomyopathy, and malignant arrhythmias
- Vaccination within 4 weeks of the first administration of study drug and throughout the study is prohibited, except for administration of inactivated vaccines (eg, inactivated influenza vaccines).
- All other underlying medical condition (including laboratory abnormalities) that is detrimental to study drug administration, or may affect drug toxicity or AE interpretation, or may result in inadequate or reduced adherence to study drug; Alcohol or drug abuse or dependence
- Pregnancy or lactation
- Concurrent participated in another therapeutic clinical trial
Trial locations and contacts
1 site in 1 country.
China1 site
Henan Cancer Hospital/The affiliated Cancer Hospital of ZhengZhou university
Zhengzhou, Henan, 450008
About this study
Official title: Cadonilimab as Neoadjuvant Therapy in Resectable Stage II-III Mismatch Repair-deficient (dMMR)/ Microsatellite Instability-high (MSI-H) Colorectal Cancer
This study will evaluate the safety, and tolerability of Cadonilimab as neoadjuvant treatment for resectable local advanced colorectal cancer patient with dMMR/MSI-H.
Read the detailed description
Colorectal cancer (CRC) is one of the most common malignant tumours of human beings. Mismatch Repair-deficient (dMMR)/ Microsatellite Instability-high (MSI-H) CRC is a specific subtype of CRC, which accounts for approximately 15% ~20% of all CRC patients,and can not benefit from 5-fluorouracil (5-FU) adjuvant chemotherapy. Once patients have distant metastases, they are not sensitive to traditional palliative chemotherapy, and thus lead to much worse prognosis than that of mismatch repair-proficient (pMMR)/ microsatellite stability (MSS). Neoadjuvant immunotherapy based on mismatch repair (MMR) status in CRC have reported some encouraging data. The NICHE study showed that 20 CRC patients with dMMR achived pathological remission, of which 19 patients with residual tumor ≤10%, 15 patients achived pathological complete remission. Another study (ClinicalTrials.gov, NCT03926338) which investigating the effect of neoadjuvant PD-1 blockade with toripalimab, with or without celecoxib, on mismatch repair-deficient or microsatellite instability-high, locally advanced, colorectal cancer. The result revealed that all 34 patients had an R0 resection. 15 of 17 patients (88%) in the toripalimab plus celecoxib group and 11 of 17 patients (65%) in the toripalimab monotherapy group had a pathological complete response.
Cadonilimab (®), a PD-1/CTLA-4 bi-specific antibody, is being developed by Akeso, Inc. for the treatment of a range of solid tumours, including cervical cancer, lung cancer, gastric/gastroesophageal junction cancer, oesophageal squamous cell cancer, liver cancer and nasopharyngeal cancer. Cadonilimab was approved in China in June 2022 for use in patients with relapsed or metastatic cervical cancer (r/mCC) who have progressed on or after platinum-based chemotherapy.
Given the reported efficacy data about immunotherapy as neoadjuvant treatment in MSI-H/dMMR CRC, the aim of this study was to investigate the efficacy and safety of Cadonilimab as neoadjuvant treatment for resectable local advanced colorectal cancer patient with the dMMR/MSI-H.
- Conditions
- Colorectal Cancer, Mismatch Repair-deficient (dMMR), Microsatellite Instability-high (MSI-H), Neoadjuvant Therapy
- Being tested
- Cadonilimab (®), a PD-1/CTLA-4 bi-specific antibody
- Medical subject headings
- Colorectal Neoplasms, Turcot syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cadonilimab (®), a PD-1/CTLA-4 bi-specific antibodyDrug
Also called Neoadjuvant therapy with Cadonilimab
10mg/kg, Q3W for 4 cycles
| Study group | Role | What they receive |
|---|---|---|
| Experimental: Cadonilimab (®), a PD-1/CTLA-4 bi-specific antibody | Experimental | Neoadjuvant therapy with Cadonilimab Receives: Drug: Cadonilimab (®), a PD-1/CTLA-4 bi-specific antibody |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pathological complete response (pCR) rates
Proportion of patients experiencing a pCR to perioperative PD-1/CTLA-4 bi-specific antibody
Measured: 1 year
Secondary outcomes (5)
Major pathological response rates
The proportion of patients experiencing a major pathological response to perioperative PD-1/CTLA-4 bi-specific antibody
Measured: 1 year
R0 resection rates
The proportion of patients experiencing a R0 resection after perioperative treatment with PD-1/CTLA-4 bi-specific antibody
Measured: 1 year
Relapse-free survival (DFS)
Defined as the time from radical surgery to relapse, metastasis or death from any cause
Measured: 3 years
The incidence of Treatment-related Adverse Events
Assessed by evaluation of treatment-related adverse events
Measured: 1 year
Number of participants with any treatment-related delays in the planned surgery of no more than 28 days after the last preoperative Cadonilimab dose
Any treatment-related delays in the planned surgery of no more than 28 days after the last preoperative Cadonilimab dose
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jun 2023
- Study start20 Jun 2023 (estimated)
- Primary completion20 Dec 2023 (estimated)
- Study completion20 Dec 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Colorectal CancerStudies of the same condition, open and under way.
- 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
- 22 participants (estimated)
Sponsor and investigators
- Lead sponsor
- LiuYing
- Sponsor type
- Other government
- Responsible party
- Sponsor-investigator, LiuYing, Henan Cancer Hospital
- Investigators
- Ying Liu, MD, Principal investigator, Henan Cancer Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05913570
- Sponsor's protocol ID
- 2023-061-002
- Acronym
- MSI-H/dMMR
- Status last verified
- Jun 2023
- First submitted
- 6 Jun 2023
- Last updated
- 22 Jun 2023
- 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 22 Jun 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cadonilimab as Neoadjuvant Therapy in Resectable Stage II-III Mismatch Repair-deficient (dMMR)/ Microsatellite Instability-high (MSI-H) Colorectal Cancer
- ClinicalTrials.gov ID
- NCT05913570
- Acronym / sponsor ID
- MSI-H/dMMR / 2023-061-002
- Conditions
- Colorectal Cancer, Mismatch Repair-deficient (dMMR), Microsatellite Instability-high (MSI-H), Neoadjuvant Therapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 22 participants (estimated)
- Lead sponsor
- LiuYingOther government
- Study start
- 20 Jun 2023 (estimated)
- Primary completion
- 20 Dec 2023 (estimated)
- Study completion
- 20 Dec 2023 (estimated)
- First posted
- 22 Jun 2023 (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.
This study will evaluate the safety, and tolerability of Cadonilimab as neoadjuvant treatment for resectable local advanced colorectal cancer patient with dMMR/MSI-H.
Detailed description
Colorectal cancer (CRC) is one of the most common malignant tumours of human beings. Mismatch Repair-deficient (dMMR)/ Microsatellite Instability-high (MSI-H) CRC is a specific subtype of CRC, which accounts for approximately 15% ~20% of all CRC patients,and can not benefit from 5-fluorouracil (5-FU) adjuvant chemotherapy. Once patients have distant metastases, they are not sensitive to traditional palliative chemotherapy, and thus lead to much worse prognosis than that of mismatch repair-proficient (pMMR)/ microsatellite stability (MSS). Neoadjuvant immunotherapy based on mismatch repair (MMR) status in CRC have reported some encouraging data. The NICHE study showed that 20 CRC patients with dMMR achived pathological remission, of which 19 patients with residual tumor ≤10%, 15 patients achived pathological complete remission. Another study (ClinicalTrials.gov, NCT03926338) which investigating the effect of neoadjuvant PD-1 blockade with toripalimab, with or without celecoxib, on mismatch repair-deficient or microsatellite instability-high, locally advanced, colorectal cancer. The result revealed that all 34 patients had an R0 resection. 15 of 17 patients (88%) in the toripalimab plus celecoxib group and 11 of 17 patients (65%) in the toripalimab monotherapy group had a pathological complete response.
Cadonilimab (®), a PD-1/CTLA-4 bi-specific antibody, is being developed by Akeso, Inc. for the treatment of a range of solid tumours, including cervical cancer, lung cancer, gastric/gastroesophageal junction cancer, oesophageal squamous cell cancer, liver cancer and nasopharyngeal cancer. Cadonilimab was approved in China in June 2022 for use in patients with relapsed or metastatic cervical cancer (r/mCC) who have progressed on or after platinum-based chemotherapy.
Given the reported efficacy data about immunotherapy as neoadjuvant treatment in MSI-H/dMMR CRC, the aim of this study was to investigate the efficacy and safety of Cadonilimab as neoadjuvant treatment for resectable local advanced colorectal cancer patient with the dMMR/MSI-H.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Experimental: Cadonilimab (®), a PD-1/CTLA-4 bi-specific antibody | Experimental | Drug: Cadonilimab (®), a PD-1/CTLA-4 bi-specific antibodyNeoadjuvant therapy with Cadonilimab |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Willing and able to provide written informed consent.
- Male or female subjects > 18 years
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Histological or cytological documentation of adenocarcinoma of the colon or rectum; Tumor tissues were identified as mismatch repair-deficient (dMMR) by immunohistochemistry (IHC) method or microsatellite instability-high (MSI-H) by polymerase chain reaction (PCR) in local site; For colon cancer must be determined by CT or MRI scans as locally advanced (T4) or cN1-2 [with the definition of a clinically positive lymph node being any node ≥ 1.0 cm]). Participants should be eligible for radical resection of R0.
- At least one measurable lesion as defined by RECIST 1.1
Key exclusion criteria (20 listed)
- Previous any systemic anticancer therapy for colorectal cancer disease, including chemotherapy, radiothapy or immunotherapy
- Previously received anti-programmed death-1 (PD-1) or its ligand (PD-L1) antibody, anti-cytotoxic T lymphocyte-associated antigen 4 (cytotoxic T-lymphocyte-associated Protein 4, CTLA-4) antibody or other drug/antibody that acts on T cell costimulation or checkpoint pathways.
- Subjects with known allergy to monoclonal antibodies
- Previous or concurrent cancer that is distinct in primary site or histology from colon cancer within 2 years prior to study drug treatment.
- Concurrent with active autoimmune disease or Participants with a history of autoimmune disease who may recur
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 |
|---|---|---|
| Cadonilimab (®), a PD-1/CTLA-4 bi-specific antibodyAlso: Neoadjuvant therapy with Cadonilimab10mg/kg, Q3W for 4 cycles | Drug | Experimental: Cadonilimab (®), a PD-1/CTLA-4 bi-specific antibody |
Primary outcome
Pathological complete response (pCR) rates
Time frame: 1 year
Proportion of patients experiencing a pCR to perioperative PD-1/CTLA-4 bi-specific antibody
5 secondary outcomes
Major pathological response rates
Time frame: 1 year
R0 resection rates
Time frame: 1 year
Relapse-free survival (DFS)
Time frame: 3 years
The incidence of Treatment-related Adverse Events
Time frame: 1 year
Number of participants with any treatment-related delays in the planned surgery of no more than 28 days after the last preoperative Cadonilimab dose
Time frame: 1 year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jun 2023.
- 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.
Ying Liu, MD principal investigator
Henan Cancer Hospital
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 Cadonilimab (®), a PD-1/CTLA-4 bi-specific antibody in people with Colorectal Cancer and Mismatch Repair-deficient (dMMR), run by LiuYing 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 20 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: status not confirmed, as of the sponsor's last update on 22 Jun 2023. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Ying Liu, MD (+86-13783604602, Yaya7207@126.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pathological complete response (pCR) rates (time frame: 1 year). 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 22 Jun 2023.