Solid Tumor
Conditions
Brief summary
This is Phase 1, Multicenter, Open-Label, Dose-Escalation and Dose-Exploration Study to Evaluate the Safety, Pharmacokinetics, and Anti-tumor Activity of AK119 (Anti-CD73) in Subjects with Advanced or Metastatic Solid Tumors.
Interventions
DRUGAK119
Subjects will receive AK119 intravenously.
Sponsors
Akeso
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age ≥ 18 years. 2. Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to1. 3. Life expectancy ≥12 weeks; 4. Females of childbearing potential must be willing to use a highly effective method of birth control for the duration of the study, and within 120 days after the last dose of investigational product. 5. Non-sterile males must be willing to use a highly effective method of birth control for the duration of the study and within 120 days after the last dose of investigational product. 6. Subjects must have histologically or cytologically confirmed advanced or metastatic solid tumor that is refractory or relapsed to the current standard therapies, or for which no effective standard therapy is available, or whereby standard therapy has been refused. 7. Subjects must have evaluable lesions according to RECIST v1.1. 8. Adequate organ function.
Exclusion criteria
1. Prior malignancy active within the previous 3 years except for the tumor for which a subject is enrolled in the study, and locally curable cancers that have been apparently cured. 2. Receipt of the following treatments or procedures: 1. Anticancer small-molecule targeted agent (e.g., tyrosine kinase inhibitor) within 2 weeks prior to the first dose of investigational product; 2. Anti-PD-1/PD-L1 mAb within 4 weeks prior to the first dose of investigational product; 3. Prior use of approved or investigational anti-CTLA-4 therapy, anti-CD73 therapy or adenosine 2A receptor inhibitors, or any other antibody or drug targeting T cell costimulation or immune checkpoint pathways such as ICOS, or agonists such as CD40, CD137, GITR, OX40 etc.; 4. Other anticancer mAb within 4 weeks or 5 half-lives (whichever is less) prior to the first dose of investigational product; 5. Other anticancer therapy (e.g., chemotherapy, radiotherapy, etc.) within 4 weeks prior to the first dose of investigational product; 6. Any major surgery within 4 weeks prior to the first dose of investigational product; 7. Any other non-approved investigational product or procedure within 4 weeks prior to the first dose of investigational product, or concurrent participation in another therapeutic clinical study; 8. Any topical therapy (e.g., TACE, HAIC, TARE) within 4 weeks prior to the first dose of investigational product; 3. Subjects with history of brain metastases that have been treated may participate provided they show evidence of stable supra-tentorial lesions at Screening; 4. Brain stem metastasis, meningeal metastasis, spinal cord metasasis or compression; 5. Uncontrolled massive ascites, pleural effusion or pericardial effusion, as determined by the Investigator; 6. Known history of human immunodeficiency virus (HIV) infection; 7. Known active hepatitis B or C infections (Active hepatitis B is defined as a known positive Hepatitis B surface antigen \[HBsAg\] result. Active hepatitis C is defined by a known positive Hepatitis C virus \[HCV\] antibody with detectable HCV ribonucleic acid \[RNA\] results); 8. Active autoimmune diseases or history of autoimmune diseases that may relapse; 9. History of interstitial lung disease, noninfectious pneumonitis except for those induced by radiation therapies; 10. Patients with clinically significant cardio-cerebrovascular or venous thromboembolic disease; 11. Toxicities of prior anticancer therapy have not resolved to NCI-CTCAE version 5.0 Grade ≤1, or to levels dictated in the inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with adverse events (AEs) | From the time of informed consent signed through 90 days after the last dose of study drug | An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product temporally associated with the use of study treatment, whether or not considered related to the study treatment. |
| Number of participants with a Dose Limiting Toxicity (DLT) | During the first 4 weeks in dose-escalation phase, during the first 3 weeks in dose-exploration phase | DLTs will be assessed during the first 4 weeks of treatment for dose-escalation phase and first 3 weeks for dose-exploration phase. DLTs 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 DLT observation period. |
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 confirmed PR. |
| Serum PK concentration of AK119 | From first dose of study drug through 30 days after last dose of study drug | Serum PK concentration of AK119 in individual subjects at different time points after AK119 administration. |
| Progression-free survival (PFS) | Up to 2 years | PFS is defined as the time from the start of treatment with AK119 until the first documentation of disease progression or death due to any cause, whichever occurs first. |
| Disease control rate (DCR) | Up to 2 years | DCR is defined as the proportion of subjects with CR, PR, or SD. |
| Number of subjects who develop detectable anti-drug antibodies (ADAs) | From first dose of study drug through 90 days after last dose of study drug | The immunogenicity of AK119 will be assessed by summarizing the number of subjects who develop detectable anti-drug antibodies (ADAs). |
Countries
China
Outcome results
None listed