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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Dose-Escalation, intranasally | Active Comparator | With a standard 3+3 dose escalation design, the enrollment will proceed until the maximum tolerated dose (MTD) has been defined or the highest dose level has been reached. |
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| Dose-Escalation, inhalation | Active Comparator | With a standard 3+3 dose escalation design, the enrollment will proceed until the MTD has been defined or the highest dose level has been reached. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Manganese Chloride | Drug | 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 |
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| Measure | Description | Time Frame |
|---|---|---|
| Number 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. | 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. | Approximately 6 months |
| Measure | Description | Time Frame |
|---|---|---|
| Preliminary efficacy evaluation | Objective response rate (ORR) and disease control rate (DCR) will be evaluated by investigators per the RECIST V1.1. | Approximately 6 months |
| The q3w pharmacokinetic profile of Manganese |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Weidong Han, M.D. | Contact | +861066937463 | hanwdrsw@sina.com |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Biotherapeutic Department of Chinese PLA General Hospital | Recruiting | Beijing | Beijing Municipality | 100853 | China |
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| ID | Term |
|---|---|
| D008223 | Lymphoma |
| D009362 | Neoplasm Metastasis |
| ID | Term |
|---|---|
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
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| ID | Term |
|---|---|
| C025340 | manganese chloride |
| C000711728 | spartalizumab |
| D000082082 | Immune Checkpoint Inhibitors |
| ID | Term |
|---|---|
| D045504 | Molecular Mechanisms of Pharmacological Action |
| D020228 | Pharmacologic Actions |
| D020164 | Chemical Actions and Uses |
| D000074322 | Antineoplastic Agents, Immunological |
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| Anti-PD-1 antibody | Drug | Administered intravenously, at 2-4mg/kg on day 3 in a 3-week cycle |
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| Systemic therapy | Combination Product | Whether and which should be given depends on the treatment regimen before enrollment. |
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PK parameters such as Maximum concentration (Cmax) are assessed.
| 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. | Approximately 3 months |
| D006425 | Hemic and Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| D009385 | Neoplastic Processes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D000970 | Antineoplastic Agents |
| D045506 | Therapeutic Uses |