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 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
