MSI-H/dMMR Solid Tumor
Conditions
Brief 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.
Interventions
DRUGAK104
AK104，6 mg/kg IV，every 2 weeks (Q2W)
Sponsors
Akeso Pharmaceuticals, Inc.
Akeso
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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. * 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.
Exclusion criteria
* 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. * 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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective response rate (ORR) | Up to 2 years | ORR is defined as the proportion of subjects with confirmed CR or PR, based on RECIST v1.1. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of response (DoR) | Up to 2 years | 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. |
| Progression-free survival (PFS) | Up to 2 years | 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. |
| Overall survival (OS) | Up to 2 years | OS is defined as the time from the start of treatment with AK104 until death due to any cause. |
| Disease control rate (DCR) | Up to 2 years | DCR is defined as the proportion of subjects with confirmed CR, PR, or SD, based on RECIST v1.1 |
| Observed pharmacokinetics (PK) exposure of AK104 | From first dose of AK104 through to 90 days after last dose of AK104 | The endpoints for assessment of PK of AK104 include serum concentrations of AK104 at different timepoints after AK104 administration. |
| Number of subjects who develop detectable anti-drug antibodies (ADAs) | From first dose of AK104 through to 90 days after last dose of AK104 | The immunogenicity of AK104 will be assessed by summarizing the number of subjects who develop detectable ADAs. |
| Adverse events (AEs) | From first dose of AK104 through to 90 days after last dose of AK104 | Incidences of treatment-emergent adverse events (TEAEs) , treatment-related adverse events (TRAEs) as assessed by CTCAE v5.0 |
Countries
China
Outcome results
None listed