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.
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
Interventions
Drug | Synonyms | Arms |
---|
EMB-02 | | EMB-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
Name | Type | Description | Interventions |
---|
EMB-02 | Experimental | In 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. | |
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