A Safety Study of the Pan-immunotherapy in Patients With Unresectable/Metastatic Solid Tumors or Lymphomas

Chinese PLA General Hospital (301 Hospital)

Status and phase: Unknown; Phase 1

Conditions: Solid Tumor; Lymphoma

Treatments: Drug: Anti-PD-1 antibody; Combination Product: Systemic therapy; Drug: Manganese Chloride

Study type: Interventional

Funder types: Other

Identifiers

NCT03991559

CHN-PLAGH-BT-039

Details and patient eligibility

About

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.

Enrollment: 20 estimated patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Subjects must have histologically proven unresectable/ metastatic solid tumors or lymphomas.
2. ≥ 18 years old.
3. Life expectancy of at least 6 months.
4. Eastern Cooperative Oncology Group performance status 0-2.
5. Subjects must have at least one measurable lesion ≥ 1 cm as defined by response criteria.
6. Subjects must have received at least two frontline therapies, except for patients initially diagnosed with local advanced or metastatic pancreatic cancer or cholangiocarcinoma.
7. Subjects must be off prior therapy for at least 4 weeks prior to Day 1. Subjects with autologous hematopoietic stem-cell transplantation are eligible which must be more than 3 months. Subjects with Anti-PD-1 antibody are eligible which must be resistance.
8. Adequate organ function.
9. Participants of childbearing potential must be willing to use an adequate method of contraception for the course of the study through 120 days after the last dose of study drug.

Exclusion criteria

1. Subjects with any autoimmune disease or history of syndrome that requires corticosteroids or immunosuppressive medications.
2. Serious uncontrolled medical disorders or active infections, pulmonary infection especially.
3. T cell lymphomas or leukemia.
4. Prior organ allograft.
5. Women who are pregnant or breastfeeding.
6. Women with a positive pregnancy test on enrollment or prior to investigational product administration.
7. Subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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20 participants in 2 patient groups

Dose-Escalation, intranasally

Active Comparator group

Description:

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.

Treatment:

Combination Product: Systemic therapy

Drug: Manganese Chloride

Drug: Anti-PD-1 antibody

Dose-Escalation, inhalation

Active Comparator group

Description:

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.

Treatment:

Combination Product: Systemic therapy

Drug: Manganese Chloride

Drug: Anti-PD-1 antibody