Clinical Trials /

A Study of EMB-02 in Participants With Advanced Solid Tumors

NCT04618393

Description:

The primary purpose of this study is to identify the recommended Phase 2 dose(s) (RP2Ds) and schedule assessed to be safe for EMB-02 and to characterize the safety and tolerability of EMB-02 at the RP2Ds. Pharmacokinetics (PK), immunogenicity, and the anti-tumor activity of EMB-02 will also be assessed.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study of EMB-02 in Participants With Advanced Solid Tumors
  • Official Title: A Phase I/II Trial of EMB-02, a Bi-specific Antibody Against PD-1 and LAG-3, in Patients With Advanced Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: EMB02X101
  • NCT ID: NCT04618393

Conditions

  • Advanced Solid Tumors

Interventions

DrugSynonymsArms
EMB-02EMB-02

Purpose

The primary purpose of this study is to identify the recommended Phase 2 dose(s) (RP2Ds) and schedule assessed to be safe for EMB-02 and to characterize the safety and tolerability of EMB-02 at the RP2Ds. Pharmacokinetics (PK), immunogenicity, and the anti-tumor activity of EMB-02 will also be assessed.

Detailed Description

      This is a Phase I/II, multi-center, open label, multiple-dose, first in human study, designed
      to assess safety and tolerability, and to identify the maximum tolerated dose (MTD) and/or
      recommended Phase 2 dose (RP2D) for EMB-02 in patients with advanced solid tumors.
      Pharmacokinetics, pharmacodynamics, immunogenicity, and response will also be assessed.
    

Trial Arms

NameTypeDescriptionInterventions
EMB-02ExperimentalIn Phase I part: participants enrolled in the different time will receive EMB-02 once weekly (IV) at different ascending dose levels. In Phase II part: participants will receive EMB-02 once weekly (IV) at previously defined RP2D.
  • EMB-02

Eligibility Criteria

        Inclusion Criteria:

          -  Willing and able to provide written informed consent.

          -  Phase I: Patients with histologically or cytologically confirmed locally
             advanced/metastatic solid tumors. Standard therapies do not exist, are no longer
             effective, or are not tolerable or accessible to the patient. And the disease is
             measurable or evaluable per RECIST v1.1

          -  Phase II Cohort A: Patients with histologically or cytologically confirmed locally
             advanced/metastatic melanoma, excluding uveal melanoma. > 1 prior therapy, including
             prior treatment with PD-1/L1(mandatory) and/or CTLA-4 inhibitors(optional). And the
             disease is measurable or evaluable per RECIST v1.1

          -  Archival tumor samples available for retrospective analysis or biopsy will be taken.

          -  ECOG performance status 0 or 1 for phase I, and ≤2 for phase II; life expectancy > 3
             Months

          -  Adequate organ function to participate in the trial.

          -  Recovery from adverse events (AEs) related to prior anticancer therapy.

          -  Highly effective contraception

        Exclusion Criteria:

          -  Patients who have active autoimmune disease or history of autoimmune disease

          -  History of severe irAE.

          -  History of severe allergic reactions

          -  Use of systemic corticosteroids.

          -  Symptomatic central nervous system metastases.

          -  Patients with cardiac dysfunction

          -  Uncontrolled diabetes mellitus with hemoglobin A1c > 8% (via medical history)

          -  Prior treatment with a LAG-3 inhibitor

          -  Anticancer therapy or radiation < 5 half-lives or 4 weeks (whichever is shorter) prior
             to study treatment;

          -  Prior organ or stem cell/bone marrow transplant.

          -  Concurrent malignancy < 5 years prior to entry.

          -  Patients with active infections.

          -  Major surgery < 4 weeks or minor surgery < 2 weeks prior to study treatment

          -  Live virus vaccines < 30 days prior to screening

          -  Pregnant or breast-feeding females

          -  Any investigational agents or study drugs from a previous clinical study within 30
             days of the first dose of study treatment

          -  Any other serious underlying medical conditions

          -  Abuse on alcohol, cannabis- derived products or other drugs
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence and severity of adverse events as assessed by CTCAE V5.0
Time Frame:Screening up to follow-up (30 days after the last dose)
Safety Issue:
Description:Incidence and severity of AE.

Secondary Outcome Measures

Measure:Area under the serum concentration-time curve (AUC) of EMB-02
Time Frame:Through treatment until EOT visit, expected average 6 months
Safety Issue:
Description:Blood samples for serum PK analysis will be obtained (AUC).
Measure:Maximum serum concentration (Cmax) of EMB-02
Time Frame:Through treatment until EOT visit, expected average 6 months
Safety Issue:
Description:Blood samples for serum PK analysis will be obtained (Cmax)
Measure:Trough concentration (Ctrough) of EMB-02
Time Frame:Through treatment until EOT visit, expected average 6 months
Safety Issue:
Description:Blood samples for serum PK analysis will be obtained (Ctrough)
Measure:Average concentration over a dosing interval (Css, avg)of EMB-02.
Time Frame:Through treatment until EOT visit, expected average 6 months
Safety Issue:
Description:Blood samples for serum PK analysis will be obtained (Css, avg).
Measure:Terminal half-life (T1/2) of EMB-02
Time Frame:Through treatment until EOT visit, expected average 6 months.
Safety Issue:
Description:Blood samples for serum PK analysis will be obtained (T1/2)
Measure:Systemic clearance (CL) of EMB-02
Time Frame:Through treatment until EOT visit, expected average 6 months
Safety Issue:
Description:Blood samples for serum PK analysis will be obtained (CL).
Measure:Steady state volume of distribution (Vss) of EMB-02
Time Frame:Through treatment until EOT visit, expected average 6 months
Safety Issue:
Description:Blood samples for serum PK analysis will be obtained (Vss).
Measure:Progression free survival (PFS) of EMB-02 as assessed by RECIST 1.1
Time Frame:From the date of dosing until the date of first documented progression or date of death from any cause, whichever came first, expected average 6 months
Safety Issue:
Description:Preliminary anti-tumor activity of EMB-02 will be obtained (PFS).
Measure:Duration of response of EMB-02 as assessed by RECIST 1.1
Time Frame:From the date of dosing until the date of first documented progression or date of death from any cause, whichever came first, expected average 6 months
Safety Issue:
Description:Preliminary anti-tumor activity of EMB-02 will be obtained (DOR).
Measure:Incidence and titer of anti-drug antibodies stimulated by EMB-02
Time Frame:Up to End of Treatment Follow Up Period (30 days after the last dose)
Safety Issue:
Description:Antibodies to EMB-02 will be assessed to evaluate potential immunogenicity.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Shanghai EpimAb Biotherapeutics Co., Ltd.

Trial Keywords

  • Phase I/II
  • Bispecific antibody
  • PD-1
  • LAG-3
  • EMB-02
  • Immuno-oncology
  • dose escalation
  • cohort expansion
  • Neoplasms
  • Neoplasm Metastasis
  • advanced solid tumor

Last Updated

January 22, 2021