Identification of T cell inhibitory signals, including PD-1/PD-L1, has prompted the development of a new class of cancer immunotherapy that could restore an adequate immunosurveillance against the neoplasm and enhance T-cell-mediated anticancer immune responses. However, elimination of cancer by T cells is only one step in the Cancer-Immunity Cycle, which enable providing several therapeutic targets and tailoring of combinations of immune therapies. Manganese has been confirmed to activate antigen-presenting cells and function as mucosal immunoadjuvants in pre-clinical studies. This study is a first-in-man, Phase I, 3 + 3 dose escalation study of a combined regimen of Manganese and anti-PD-1 antibody with or without chemotherapies in subjects with unresectable/ metastatic solid tumors or lymphomas. This study is designed to assess the safety, tolerability, pharmacokinetic profile (PK profile), mode of delivery and Recommended Phase 2 Dose (RP2D) of this regimen.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
20
Administered intranasally in Arm 1 (0.05, 0.1 or 0.2 mg/kg/d) and by inhalation in Arm 2 (0.1, 0.2 or 0.4mg/kg/d) once daily in a 3-week cycle
Administered intravenously, at 2-4mg/kg on day 3 in a 3-week cycle
Whether and which should be given depends on the treatment regimen before enrollment.
Biotherapeutic Department of Chinese PLA General Hospital
Beijing, Beijing Municipality, China
RECRUITINGNumber of Subjects with treatment-related adverse events (AEs)
Incidence, nature, and severity of adverse events graded according to the NCI CTCAE v5.0. AEs were considered to be treatment-related if they had started or worsened within the interval from first study drug administration until the follow-up visit.
Time frame: Approximately 6 months
Number of subjects with specific Manganese-related adverse events
Manganese-related AEs were considered to be that start or worsen after administration Manganese administration,improve after withdrawal, and even occur again after re-administration.
Time frame: Approximately 6 months
Preliminary efficacy evaluation
Objective response rate (ORR) and disease control rate (DCR) will be evaluated by investigators per the RECIST V1.1.
Time frame: Approximately 6 months
The q3w pharmacokinetic profile of Manganese
PK parameters such as Maximum concentration (Cmax) are assessed.
Time frame: Approximately 3 months
Number of participants with laboratory test abnormalities
The laboratory tests of serum cytokines and chemokines will be performed on day 1 and 3 of each cycle, and the abnormality will be determined by the investigator.
Time frame: Approximately 3 months
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