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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Advanced Solid Tumors

Intervention / Treatment
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* Biological: EMB-02


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Dose escalation followed by Cohort Expansion Phase at the RP2D.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: EMB-02<br>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. | Biological: EMB-02<br>* EMB-02 is a FIT-Ig® bispecific antibody against PD-1 and LAG-3.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and severity of adverse events as assessed by CTCAE V5.0 | Incidence and severity of AE. | Screening up to follow-up (30 days after the last dose) | 
| Incidence of serious adverse events (SAE) | Incidence of SAE. | Screening up to follow-up (30 days after the last dose) | 
| Incidence of dose interruptions | Incidence of dose interruptions of EMB-02 during treatment as a measure of tolerability. | Screening up to follow-up (30 days after the last dose) | 
| Dose intensity | Actual amount of drug taken by patients divided by the planned amount. | Screening up to follow-up (30 days after the last dose) | 
| The incidence of DLTs during the first cycle of treatment. | The Dose Limiting Toxicities (DLTs) are based on drug related adverse events and are specifically defined in study protocol. | First infusion to the end of Cycle 1 (each cycle is 28 days) | 
| Overall Response Rate (ORR) | Measured by RECIST 1.1, only applicable in Phase II part | 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 | 

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Phase I/II, Bispecific antibody, PD-1, LAG-3, EMB-02, Immuno-oncology, dose escalation, cohort expansion, Neoplasms, Neoplasm Metastasis, advanced solid tumor