The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK), immunogenicity, pharmacodynamics (PD) and anti-tumor activities of AK104,a PD-1/CTLA-4 bispecific antibody, when administered as a single agent in adults subjects with advanced or metastatic solid tumors, or combined with oxaliplatin and capecitabine as first-line therapy in adult subjects with advanced unresectable or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma.
The study consists of a dose escalation and expansion phase (Phase Ib) to determine the recommended Phase 2 dose (RP2D) for AK104 in combination with oxaliplatin and capecitabine, and a dose confirmation phase (Phase II) which will further characterize the treatment of AK104 in combination at the RP2D.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
338
Subjects will receive AK104 by intravenous administration.
Subjects will receive AK104 in combination with oxaliplatin and capecitabine.
Subjects will receive AK104 in combination with oxaliplatin and capecitabine.
Beijing Cancer Hospital
Beijing, Beijing Municipality, China
The number of subjects experiencing adverse events (AEs) (Phase Ib)
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.
Time frame: From the time of informed consent through 90 days following termination of treatment with investigational product
The number of subjects experiencing dose-limiting toxicities (DLTs) (Phase Ib)
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.
Time frame: During the first 4 weeks
Anti-tumor activity of AK104 using objective response rate (ORR) based on RECIST v1.1 as assessed by the investigator (Phase II)
The ORR is defined as the proportion of subjects with confirmed CR or confirmed PR, based on RECIST Version 1.1.
Time frame: From the first dose of study drug through the date of first documented progression, end of study, date of death, or one year after the last patient starts treatment, whichever should occur first
Disease control rate (DCR)
The DCR is defined as the proportion of subjects with CR, PR, or SD (subjects achieving SD will be included in the DCR if they maintain SD for ≥8 weeks) based on RECIST Version 1.1.
Time frame: Up to 2 years
Duration of response (DoR)
Duration of response 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.
Time frame: Up to 2 years
Progression-free survival (PFS)
Progression-free survival 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.
Time frame: Up to 2 years
Overall survival (OS)
Overall survival is defined as the time from the start of treatment with AK104 until death due to any cause.
Time frame: Up to 2 years
Maximum observed concentration (Cmax) of AK104
The endpoints for assessment of PK of AK104 include serum concentrations of AK104 at different timepoints after AK104 administration.
Time frame: From first dose of AK104 through to 90 days after last dose of AK104
Minimum observed concentration (Cmin) of AK104 at steady state
The endpoints for assessment of PK of AK104 include serum concentrations of AK104 at different timepoints after AK104 administration.
Time frame: From first dose of AK104 through to 90 days after last dose of AK104
Area under the curve (AUC) of AK104
The endpoints for assessment of PK of AK104 include serum concentrations of AK104 at different timepoints after AK104 administration.
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)
The immunogenicity of AK104 will be assessed by summarizing the number of subjects who develop detectable anti-drug antibodies (ADAs).
Time frame: From first dose of AK104 through 90 days after last dose of AK104
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