Solid Tumor
Conditions
Brief summary
This is a first in human(FIH) study to characterize the safety, tolerability, pharmacokinetics (PK), immunogenicity and anti-tumor activity of AK109, an anti-VEGFR2 monoclonal antibody, as a single agent in adult subjects with advanced solid tumor.
Interventions
DRUGAK109
AK109, 2#4#8#12#18mg/kg, IV, every 2 weeks (Q2W), or 15 mg/kg every 3 weeks(Q3W)
Sponsors
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. * Histologically or cytologically documented advanced solid tumor that is refractory/relapsed/intolerant to standard therapies, or for which no effective standard therapy is available, or subject refuses standard therapy. * Have radiologically measurable disease based on RECIST 1.1 * ECOG of 0 or 1. * Estimated life expectancy of ≥3 months. * 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
* have been diagnosed other advanced tumors within 2 years before the first use of the study drug, except for the cured localized tumors. * with active central nervous system metastasis, cancerous meningitis, or spinal cord compression. * Prior use of any anti-VEGF or anti-VEGFR antibodies. * Receipt of anti-tumor treatment, other study drug, major surgery, or serious infection within 4 weeks prior to C1D1 (Cycle 1 Day1, the first dose of study drug). * Have received central venous catheterization within 7 days prior to C1D1. * Severe or uncontrolled cardiovascular and cerebrovascular diseases. * Uncontrolled hypertension. * have a high risk of bleeding. * Uncontrolled gastrointestinal diseases. * Uncontrolled pleural/pericardial or peritoneal effusion. * Have occurred any thromboembolic event, non-gastrointestinal fistula or female genital tract fistula within 6 monthsprior to C1D1. * With cirrhosis of Child-Pugh B or C. * Active or unstable viral hepatitis; or active tuberculosis. * Known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation. * received live vaccines prior 30 days within the first dose. * take apart in other clinical studies at the same time. * known to be allergic to any component of AK109, other monoclonal antibodies or any therapeutic protein. * mental illness, drug abuse, or alcohol dependence that may affect compliance with the test requirements. * Any treatment risk or condition that interferes with the study by the investigator judged.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of subjects experiencing dose-limiting toxicities (DLTs) | During the first 4 weeks | DLTs will be assessed during the first 4 weeks of treatment for dose-escalation phase and are defined as toxicities that meet pre-defined severity criteria, and assessed as having a suspected relationship to study drug, and unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurs within the first cycle (4 weeks) of treatment. |
Secondary
| 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. |
| 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. |
| Progression-free survival (PFS) | Up to 2 years | PFS is defined as the time from the start of treatment with AK109 until the first documentation of disease progression or death due to any cause, whichever occurs first. |
| Adverse events (AEs) | From the time of informed consent signed through to 60 days after last dose of AK109 | An adverse event (AE) is any untoward medical occurrence or the deterioration of existing medical event in a clinical study subject administered an investigational drug, which does not necessarily have an unequivocal causal relationship with the investigational product. Incidences of treatment-emergent adverse events (TEAEs) , treatment-related adverse events (TRAEs) as assessed by CTCAE v5.0. |
| Observed pharmacokinetics (PK) exposure of AK109 | From first dose of AK109 through 30 days after last dose of AK109 | The endpoints for assessment of PK of AK109 include serum concentrations of AK109 at different timepoints after AK109 administration. |
| Number of subjects who develop detectable anti-drug antibodies (ADAs) | From first dose of AK109 through 30 days after last dose of AK109 | The immunogenicity of AK109 will be assessed by summarizing the number of subjects who develop detectable ADAs. |
| Overall survival (OS) | Up to 2 years | OS is defined as the time from the start of treatment with AK109 until death due to any cause. |
Countries
China
Outcome results
None listed