This study was a phase IB, single-center, open-label, two part(part A involved dose reduction, and part B involved cohort expansion) clinical trial evaluating the safety and clinical activity of AK104 or AK112 in combination with axitinib in patients with advanced mucosal melanoma.
The planned cohorts in part A were axitinib 5mg twice a day plus AK104 or AK112 every 3 weeks. A minimum of three patients were initially enrolled at the first dose level. If a dose-limiting toxicity occurred, then the cohort would be expanded to a total of six patients. Responses were evaluated by investigators using both RECIST version 1.1 and Immune-Related RECIST (irRECIST). Patients with progressive disease or an intolerant toxicity were taken off the study. Patients who initially developed progressive disease per RECIST version 1.1 were allowed to continue therapy if the investigator considered patients to be benefiting from the treatment per irRECIST. Any dose-reduction cohort that did not exceed the maximum-tolerated dose could be expanded in part B for additional evaluation of safety and clinical activity. The primary end point of this study was dose-limiting toxicity within the first 4 weeks of treatment with AK104 or AK112 plus axitinib in part A.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
60
Subjects receive AK104 10mg/kg intravenously (IV) every 3-week cycle plus Axitinib until progression.
Subjects receive AK112 20mg/kg intravenously (IV) every 3-week cycle plus Axitinib until progression.
Beijing Cancer Hospital
Beijing, China
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Safety assessments including vital signs, laboratory tests, and adverse event monitoring
Time frame: 3 years
Objective Response Rate (ORR) by irRC and RECIST 1.1
The treatment effect of AK104 or AK112 in combination with axitinib, will be assessed using irRC and RECIST 1.1 to determine tumor response.
Time frame: 3 years
Duration of Response (DOR) by irRC and RECIST 1.1
The treatment effect of AK104 or AK112 in combination with axitinib, will be assessed using irRC and RECIST 1.1 to determine duration of response.
Time frame: 3 years
Disease Control Rate (DCR) by irRC and RECIST 1.1
The treatment effect of AK104 or AK112 in combination with axitinib, will be assessed using irRC and RECIST 1.1 to determine disease control rate.
Time frame: 3 years
Time to response (TTR) by irRC and RECIST 1.1
The treatment effect of AK104 or AK112 in combination with axitinib, will be assessed using irRC and RECIST 1.1 to determine time to response.
Time frame: 3 years
Progression-free survival(PFS) by irRC and RECIST 1.1
The treatment effect of AK104 or AK112 in combination with axitinib, will be assessed using irRC and RECIST 1.1 to determine progression-free survival time.
Time frame: 3 years
Overall survival (OS) by irRC and RECIST 1.1
The treatment effect of AK104 or AK112 in combination with axitinib, will be assessed using irRC and RECIST 1.1 to determine overall survival.
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Time frame: 3 years