Clinical trial NCT03991559: A Safety Study of the Pan-immunotherapy in Patients With Unresectable/Metastatic Solid Tumors or Lymphomas
Official title: A Phase I, Two-arm, Open-label, Single-center, Dose-escalation Study to Evaluate the Safety, Tolerability and Recommended Dose and Delivery Mode of the Pan-immunotherapy in Subjects With Unresectable/ Metastatic Solid Tumors or Lymphomas
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Solid Tumor
Lymphoma
Keywords: anti-PD-1 antibody
Manganese
unresectable
metastatic
Lead sponsor: Chinese PLA General Hospital
Sponsor class: OTHER
First posted: 2019-06-19
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Number of Subjects with treatment-related adverse events (AEs)
timeFrame: Approximately 6 months
measure: Number of subjects with specific Manganese-related adverse events
timeFrame: Approximately 6 months
Secondary outcomes:
measure: Preliminary efficacy evaluation
timeFrame: Approximately 6 months
measure: The q3w pharmacokinetic profile of Manganese
timeFrame: Approximately 3 months
measure: Number of participants with laboratory test abnormalities
timeFrame: Approximately 3 months
Other outcomes:
Locations:
city: Beijing
country: China
facility: Biotherapeutic Department of Chinese PLA General Hospital
state: Beijing
Study officials:
References: