MSI-H/dMMR Solid TumorPhase 2NCT04547101
A Study of AK104 in Subjects With Locally Advanced Unresectable or Metastatic MSI-H/dMMR Solid Tumors
A Phase 2 study testing AK104 in people with MSI-H/dMMR Solid Tumor, run by Akeso at 1 site in China.
Trial summary
It is a single-arm, open-label, multicenter, phase II study to evaluate the safety, efficacy, pharmacokinetics (PK) and immunogenicity of AK104 as a single agent in subjects with previously-treated locally advanced unresectable or metastatic MSI-H or dMMR solid tumors. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- MSI-H/dMMR Solid Tumor
- What is being tested?
- AK104
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 1 siteChina
- Study dates
- 24 Apr 2020to 30 Sep 2022
- 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
- Have signed written informed consent form voluntarily.
- Male or female, age ≥ 18 years on the day of signing informed consent form.
- ECOG of 0 or 1.
- Estimated life expectancy of ≥3 months.
- Histologically or cytologically documented locally advanced unresectable or metastatic solid tumors.
- Confirmed MSI-H/dMMR status by the central laboratory.
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- Have experienced documented disease progression during or after at least first-line therapy.
- Have radiologically measurable disease based on RECIST 1.1.
- Adequate organ function.
- Have agreed to take effective contraception from the date of signing the informed consent form until 120 days after the last administration.
Who cannot join
- Prior use of investigational products or devices within 4 weeks prior to C1D1 (Cycle 1 Day 1, the first dose of study drug).
- Presence of active autoimmune disease that have received systematic treatment in the past 2 years; or that is judged to be possibly relapsed or requires planned treatment by investigators.
- Active inflammatory bowel disease or that required treatment (e.g. Crohn's disease, ulcerative colitis or chronic diarrhea).
- Prior use of systematic corticosteroid (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days prior to C1D1.
- Prior exposure to tumor immunotherapy, such as checkpoint inhibitors (eg. anti-PD-1, anti-PD-L1, anti-CTLA-4 antibody), checkpoint agonists or cellular therapy.
- Known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation.
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- Known presence or history of interstitial lung disease.
- History of gastrointestinal perforation and/or fistula within 6 months prior to C1D1.
- Serious infections within 4 weeks prior to C1D1.
- Known presence of active tuberculosis.
- Known untreated chronic hepatitis B or chronic hepatitis B virus DNA exceeding 1000 IU/ mL or active hepatitis C virus.
- Receipt of recent radiotherapy or anti-tumor treatment within 4 weeks prior to C1D1.
- Presence of meningeal metastasis, spinal cord compression, leptomeningeal disease or central nervous system metastasis, with some exceptions.
- Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage.
- Unresolved toxicities from prior anticancer therapy, defined as having not resolved to NCI CTCAE v5.0 Grade 0 or 1, or to levels dictated in the inclusion/exclusion criteria. Hair loss is excluded
- Known history of sever hypersensitivity reaction to other monoclonal antibodies.
- Known history of allergy or hypersensitivity to AK104 or any of its components.
- Any conditions that, in the investigator's opinion, may put subjects treated with the study drug at risks, or interfere with the evaluation of study drug or subject safety, or the interpretation of results.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Single-arm, Open-label, Multicenter, Phase II Study of AK104, a PD-1/CTLA-4 Bispecific Antibody, in Subjects With Locally Advanced Unresectable or Metastatic Microsatellite Instability-High (MSI-H) or Mismatch Repair Deficient (dMMR) Solid Tumors
It is a single-arm, open-label, multicenter, phase II study to evaluate the safety, efficacy, pharmacokinetics (PK) and immunogenicity of AK104 as a single agent in subjects with previously-treated locally advanced unresectable or metastatic MSI-H or dMMR solid tumors.
- Conditions
- MSI-H/dMMR Solid Tumor
- Being tested
- AK104
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AK104Drug
AK104，6 mg/kg IV，every 2 weeks (Q2W)
| Study group | Role | What they receive |
|---|---|---|
| AK104 | Experimental | Not described Receives: Drug: AK104 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective response rate (ORR)
ORR is defined as the proportion of subjects with confirmed CR or PR, based on RECIST v1.1.
Measured: Up to 2 years
Secondary outcomes (7)
Disease control rate (DCR)
DCR is defined as the proportion of subjects with confirmed CR, PR, or SD, based on RECIST v1.1
Measured: Up to 2 years
Duration of response (DoR)
DoR is defined as the duration from the first documentation of objective response to the first documented disease progression or death due to any cause, whichever occurs first.
Measured: Up to 2 years
Progression-free survival (PFS)
PFS is defined as the time from the start of treatment with AK104 until the first documentation of disease progression or death due to any cause, whichever occurs first.
Measured: Up to 2 years
Overall survival (OS)
OS is defined as the time from the start of treatment with AK104 until death due to any cause.
Measured: Up to 2 years
Adverse events (AEs)
Incidences of treatment-emergent adverse events (TEAEs) , treatment-related adverse events (TRAEs) as assessed by CTCAE v5.0
Measured: From first dose of AK104 through to 90 days after last dose of AK104
Observed pharmacokinetics (PK) exposure of AK104
The endpoints for assessment of PK of AK104 include serum concentrations of AK104 at different timepoints after AK104 administration.
Measured: From first dose of AK104 through to 90 days after last dose of AK104
Number of subjects who develop detectable anti-drug antibodies (ADAs)
The immunogenicity of AK104 will be assessed by summarizing the number of subjects who develop detectable ADAs.
Measured: From first dose of AK104 through to 90 days after last dose of AK104
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Sep 2020
- Study start24 Apr 2020
- Primary completion30 Sep 2022
- Study completion30 Sep 2022
Why it stopped: Due to difficuty of erollment and consideration of clinical guideline,The sponsor decided to stop study.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for MSI-H/dMMR Solid TumorStudies of the same condition, open and under way.
- More trials run by AkesoThe 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
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- Akeso
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Akeso Pharmaceuticals, Inc.
- Responsible party
- Sponsor
- Investigators
- Ruihua Xu, MD, Principal investigator, Sun Yat-sen University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04547101
- Sponsor's protocol ID
- AK104-205
- Status last verified
- Oct 2022
- First submitted
- 7 Sep 2020
- Last updated
- 19 Oct 2022
- 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 19 Oct 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single-arm, Open-label, Multicenter, Phase II Study of AK104, a PD-1/CTLA-4 Bispecific Antibody, in Subjects With Locally Advanced Unresectable or Metastatic Microsatellite Instability-High (MSI-H) or Mismatch Repair Deficient (dMMR) Solid Tumors
- ClinicalTrials.gov ID
- NCT04547101
- Acronym / sponsor ID
- AK104-205
- Conditions
- MSI-H/dMMR Solid Tumor
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Due to difficuty of erollment and consideration of clinical guideline,The sponsor decided to stop study.
- Enrolment
- 6 participants (actual)
- Lead sponsor
- AkesoIndustry (pharma, biotech, devices)
- Collaborators
- Akeso Pharmaceuticals, Inc.
- Study start
- 24 Apr 2020 (actual)
- Primary completion
- 30 Sep 2022 (actual)
- Study completion
- 30 Sep 2022 (actual)
- First posted
- 14 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.
It is a single-arm, open-label, multicenter, phase II study to evaluate the safety, efficacy, pharmacokinetics (PK) and immunogenicity of AK104 as a single agent in subjects with previously-treated locally advanced unresectable or metastatic MSI-H or dMMR solid tumors.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| AK104 | Experimental | Drug: AK104 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Have signed written informed consent form voluntarily.
- Male or female, age ≥ 18 years on the day of signing informed consent form.
- ECOG of 0 or 1.
- Estimated life expectancy of ≥3 months.
- Histologically or cytologically documented locally advanced unresectable or metastatic solid tumors.
Key exclusion criteria (18 listed)
- Prior use of investigational products or devices within 4 weeks prior to C1D1 (Cycle 1 Day 1, the first dose of study drug).
- Presence of active autoimmune disease that have received systematic treatment in the past 2 years; or that is judged to be possibly relapsed or requires planned treatment by investigators.
- Active inflammatory bowel disease or that required treatment (e.g. Crohn's disease, ulcerative colitis or chronic diarrhea).
- Prior use of systematic corticosteroid (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days prior to C1D1.
- Prior exposure to tumor immunotherapy, such as checkpoint inhibitors (eg. anti-PD-1, anti-PD-L1, anti-CTLA-4 antibody), checkpoint agonists or cellular therapy.
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 |
|---|---|---|
| AK104AK104，6 mg/kg IV，every 2 weeks (Q2W) | Drug | AK104 |
Primary outcome
Objective response rate (ORR)
Time frame: Up to 2 years
ORR is defined as the proportion of subjects with confirmed CR or PR, based on RECIST v1.1.
7 secondary outcomes
Disease control rate (DCR)
Time frame: Up to 2 years
Duration of response (DoR)
Time frame: Up to 2 years
Progression-free survival (PFS)
Time frame: Up to 2 years
Overall survival (OS)
Time frame: Up to 2 years
Adverse events (AEs)
Time frame: From first dose of AK104 through to 90 days after last dose of AK104
Observed pharmacokinetics (PK) exposure of AK104
Time frame: From first dose of AK104 through to 90 days after last dose of AK104
Number of subjects who develop detectable anti-drug antibodies (ADAs)
Time frame: From first dose of AK104 through to 90 days after last dose of AK104
Results and safety
The study was stopped early (reason given: Due to difficuty of erollment and consideration of clinical guideline,The sponsor decided to stop study.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Oct 2022.
- 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.
Ruihua Xu, MD principal investigator
Sun Yat-sen University
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 in people with MSI-H/dMMR Solid Tumor, run by Akeso 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 10 inclusion and 18 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: stopped early, as of the sponsor's last update on 19 Oct 2022. 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?
The study was stopped early (reason given: Due to difficuty of erollment and consideration of clinical guideline,The sponsor decided to stop study.). Results are not available in the source record.
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?
Objective response rate (ORR) (time frame: Up to 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 19 Oct 2022.