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 and have failed (progressed on, or are intolerant of)
             standard therapies. Moreover, the disease should be 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

February 8, 2021