A Ph1/2 Study of EMB-06 in Participants With Relapsed or Refractory Myeloma

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-06 and to characterize the safety and tolerability of EMB-06 at the RP2Ds. Pharmacokinetics (PK), immunogenicity, and the anti-multiple myeloma activity of EMB-06 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-06 in patients with relapsed or refractory multiple myeloma. Pharmacokinetics, pharmacodynamics, immunogenicity, and response will also be assessed.

Official Title
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A First-in-human, Phase I/II, Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Antitumor Activity of EMB-06 in Patients With Relapsed or Refractory Multiple Myeloma

Conditions
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Relapsed or Refractory Multiple Myeloma

Intervention / Treatment
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* Biological: EMB-06


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Able to understand and willing to sign the informed consent form (ICF) Patients who have been diagnosed with multiple myeloma according to IMWG diagnostic criteria 2014 and have relapsed or refractory multiple myeloma with at least one measurable lesion. The patient must have received at least two lines (for patients in the US, at least three lines which should include anti-CD38 antibody) of prior antimyeloma therapies, and must have received treatment with proteasome inhibitors, immunomodulatory agents, and if accessible, an anti-CD38 targeting monoclonal antibody. ECOG performance status 0 or 1 for phase I, and ≤2 for phase II. Adequate organ function and reasonable laboratory test results to participate in the trial. Highly effective contraception Exclusion Criteria: Life expectancy is less than 3 months. Patient participated in any other clinical study within 1 month prior to enrollment in this clinical study. Patients with ongoing AE. Previously treated with any BCMA-targeted therapy.(Exception: in Phase 2 portion, up to 10 patients who have received prior anti-BCMA ADC or BCMA targeted CAR-T can be enrolled) History of allogeneic stem cell transplantation. Previously treated with the following anti-tumor therapy (prior to first dosing of EMB-06) Treated with monoclonal antibody for multiple myeloma within 28 days Treated with proteasome inhibitors within 14 days Treated with immunomodulatory agents within 14 days Treated with cytotoxic therapy within 14 days Received investigational drug within 28 days or at least 5 half-lives, whichever is shorter (if a, b, c, d not applicable) Received radiotherapy within 21 days. Except that the radiation portal covered ≤ 5% of the bone marrow reserve, the patient will be eligible to participate in the study regardless of the end date of radiation therapy Plasmapheresis within 7 days Patient received autologous stem cell transplantation within 12 weeks prior to the start of study treatment. Active or historically multiple myeloma related central nervous system involvement. Patients requiring high dose of systemic treatment with corticosteroids. Patients with active infections, including COVID-19, hepatitis, etc.. History of severe allergic reactions Patients with severe or uncontrolled cardiovascular disorder requiring treatment Pre-existing other serious medical conditions

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-06<br>In Phase I part: participants enrolled at different time will receive EMB-06 by IV infusion at different ascending dose levels. In Phase II part: participants will receive EMB-06 by IV infusion at previously defined RP2D. | Biological: EMB-06<br>* EMB-06 is a FIT-Ig® bispecific antibody against BCMA and CD3.<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 | 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-06 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 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 IMWG criteria, 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-06. | 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-06. | Blood samples for serum PK analysis will be obtained (Cmax). | Through treatment until EOT visit, expected average 6 months | 
| Trough concentration (Ctrough) of EMB-06. | 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-06. | 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-06. | 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-06. | 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-06. | 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-06 as assessed by IMWG criteria. | Preliminary anti-multiple myeloma activity of EMB-06 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-06 as assessed by IMWG criteria | Preliminary anti-multiple myeloma activity of EMB-06 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-06. | Antibodies to EMB-06 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, BCMA, CD3, EMB-06, Immuno-oncology, Dose escalation, Cohort expansion, Relapsed or Refractory Multiple Myeloma, Hematological malignancy