Phase Ia: single-dose escalation study: accelerated titration combined with traditional "3+3" dose. Sample size is correlated with the DLT occurring in each dose group. 4 dose groups are expected; the first dose group is the accelerated titration group, which includes only 1 subject; subsequent dose groups are in traditional "3+3" dose increments, with 3-6 subjects in each group; a total of 10-19 subjects are expected in all dose groups. If the DLT is still not present in the highest dose ,the safety monitoring committee(SMC) to determine if it is necessary to continue incrementally to a higher dose.
P-IL-2 injection was injected intravenously, the screening period was 28 days, and the DLT observation period was 28 days from the beginning of the first infusion (including the day of administration). After the end of the DLT observation period, subjects can continue to receive treatment on a voluntary basis. The safety follow-up after drug withdrawal was carried out 28 days after the last medication. During the survival follow-up after drug withdrawal, imaging examination and survival information were collected every 12 weeks as far as possible within 2 years after drug withdrawal, until the subjects developed disease or received other anti-tumor specific therapy. Subjects with disease progression or other treatment received telephone survival follow-up every 12 weeks. After 2 years of drug withdrawal, telephone survival follow-up was conducted every 12 weeks according to the wishes of the subjects.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
10
Ia :Single dose intravenous injection of P-IL-2;
Ib:P-IL-2 plus Anti-PD-1 Monoclonal Antibody;
First affiliated hospital, Zhejiang University
Hangzhou, Zhejiang, China
RECRUITINGthe number and severity of DLTs.
DLT refers to toxicities that occur within 28 days of the subject's first dose and are judged by the investigator to be related to the study drug and meet the following conditions, including any ≥4 hematologic toxicity and non-hematologic toxicity. All toxicity or adverse events (AEs) are graded according to NCI-CTCAE 5.0.
Time frame: 28 days after infusion
Incidence of AE and SAE
Incidence and Severity of AE and SAE; An AE was any untoward medical occurrence after clinical study subjects receive study drug. An SAE was any event that meets any the following criteria: death, life-threatening; inpatient hospitalization or prolongation, persistent or significant disability/incapacity; congenital malformation/birth defects and significant medical events. AE and SAE were graded by CTCAE version 5.0 by severity, from Grade 1 mild to Grade 5 death related AE.
Time frame: 24 month after infusion
Number of participants with physical examinations
Make list of patients who were normal before administration and abnormal after administration, physical examinations includes general appearance and examinations of the skin, eyes, ears, nose, throat, lungs, heart, abdomen, limbs, musculoskeletal system, nervous system and lymphatic system.
Time frame: 24 months after infusion
changes in the number of CD3+ cells relative to the baseline.
Peripheral blood collection, number of CD3+ cells is detected by qPCR
Time frame: Within 28 days after infusion
changes of immunoglobulin IgG relative to the baseline.
Peripheral blood collection, to monitor the changes of IgG
Time frame: Within 28 days after infusion
changes of immunoglobulin IgE relative to the baseline.
Peripheral blood collection, to monitor the changes of IgE
Time frame: Within 28 days after infusion
changes of cytokines relative to the baseline
Peripheral Blood collection,cytokines include IFN-γ、TNF-α、IL-2、IL-6、IL-10
Time frame: Within 28 days after infusion
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