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

NCT03991559 | Unknown Phase 1 DMC

• 1 other identifier: CHN-PLAGH-BT-039
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

Solid Tumor; Lymphoma

Keywords

anti-PD-1 antibody; Manganese; unresectable; metastatic

Outcome Measures

Primary Outcomes (2)

• 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

Secondary Outcomes (3)

• Preliminary efficacy evaluation

  Approximately 6 months

• The q3w pharmacokinetic profile of Manganese

  Approximately 3 months

• Number of participants with laboratory test abnormalities

  Approximately 3 months

Study Arms (2)

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.

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

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.

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

Interventions

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

Dose-Escalation, inhalation; Dose-Escalation, intranasally

Anti-PD-1 antibody DRUG

Administered intravenously, at 2-4mg/kg on day 3 in a 3-week cycle

Also known as: Anti-PD-1 monoclonal antibody, PD-1 inhibitor

Dose-Escalation, inhalation; Dose-Escalation, intranasally

Systemic therapy COMBINATION_PRODUCT

Whether and which should be given depends on the treatment regimen before enrollment.

Dose-Escalation, inhalation; Dose-Escalation, intranasally

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must have histologically proven unresectable/ metastatic solid tumors or lymphomas.
• ≥ 18 years old.
• Life expectancy of at least 6 months.
• Eastern Cooperative Oncology Group performance status 0-2.
• Subjects must have at least one measurable lesion ≥ 1 cm as defined by response criteria.
• Subjects must have received at least two frontline therapies, except for patients initially diagnosed with local advanced or metastatic pancreatic cancer or cholangiocarcinoma.
• 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.
• Adequate organ function.
• 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.

You may not qualify if:

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

Sponsors & Collaborators

• Chinese PLA General Hospital: lead

Study Sites (1)

Biotherapeutic Department of Chinese PLA General Hospital

Beijing, Beijing Municipality, 100853, China

RECRUITING

MeSH Terms

Conditions

Lymphoma; Neoplasm Metastasis

Interventions

manganese chloride; spartalizumab; Immune Checkpoint Inhibitors

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Antineoplastic Agents, Immunological; Antineoplastic Agents; Therapeutic Uses

Central Study Contacts

Weidong Han, M.D.

CONTACT

+861066937463; hanwdrsw@sina.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 14, 2019
• First Posted: June 19, 2019
• Study Start: November 1, 2018
• Primary Completion: December 31, 2019
• Study Completion: May 31, 2020
• Last Updated: August 28, 2019

Record last verified: 2019-08

Locations

CN (1)