A Study of Anti-VEGFR2 AK109 in Subjects With Advanced Solid Tumors

Study Overview
=================
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.

Official Title
-----------------
A Phase I, Open-label, Dose-escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Antitumor Activity of AK109，an Anti-VEGFR2 Monoclonal Antibody in Subjects With Advanced Solid Tumors

Conditions
-----------------
Solid Tumor

Intervention / Treatment
-----------------
* Drug: AK109


Participation Criteria
=================
Eligibility Criteria
-----------------
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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AK109<br> | Drug: AK109<br>* AK109, 2#4#8#12#18mg/kg, IV, every 2 weeks (Q2W), or 15 mg/kg every 3 weeks(Q3W)<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of subjects experiencing dose-limiting toxicities (DLTs) | 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. | During the first 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events (AEs) | 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. | From the time of informed consent signed through to 60 days after last dose of AK109 | 
| Objective response rate (ORR) | ORR is defined as the proportion of subjects with confirmed CR or PR, based on RECIST v1.1. | Up to 2 years | 
| Disease control rate (DCR) | DCR is defined as the proportion of subjects with confirmed CR, PR, or SD, based on RECIST v1.1. | Up to 2 years | 
| Progression-free survival (PFS) | 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. | Up to 2 years | 
| Overall survival (OS) | OS is defined as the time from the start of treatment with AK109 until death due to any cause. | Up to 2 years | 
| Observed pharmacokinetics (PK) exposure of AK109 | The endpoints for assessment of PK of AK109 include serum concentrations of AK109 at different timepoints after AK109 administration. | From first dose of AK109 through 30 days after last dose of AK109 | 
| Number of subjects who develop detectable anti-drug antibodies (ADAs) | The immunogenicity of AK109 will be assessed by summarizing the number of subjects who develop detectable ADAs. | From first dose of AK109 through 30 days after last dose of AK109 |