A Ph1/2 Study of EMB-06 in Participants With Relapsed or Refractory Myeloma
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
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-06 in patients with relapsed or refractory multiple myeloma. Pharmacokinetics, pharmacodynamics, immunogenicity, and response will also be assessed.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: EMB-06 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
EMB-06 is a FIT-Ig® bispecific antibody against BCMA and CD3.
|
Outcome Measures
Primary Outcome Measures
- Incidence and severity of adverse events [Screening up to follow-up (30 days after the last dose)]
Incidence and severity of AE.
- Incidence of serious adverse events (SAE) [Screening up to follow-up (30 days after the last dose)]
Incidence of SAE
- Incidence of dose interruptions. [Screening up to follow-up (30 days after the last dose)]
Incidence of dose interruptions of EMB-06 during treatment as a measure of tolerability.
- Dose intensity [Screening up to follow-up (30 days after the last dose)]
Actual amount of drug taken by patients divided by the planned amount.
- The incidence of DLTs during treatment. [First infusion to the end of Cycle 1 (each cycle is 28 days)]
The Dose Limiting Toxicities (DLTs) are based on drug related adverse events and are specifically defined in study protocol.
- Overall Response Rate (ORR) [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]
Measured by IMWG criteria, only applicable in Phase II part
Secondary Outcome Measures
- Area under the serum concentration-time curve (AUC) of EMB-06. [Through treatment until EOT visit, expected average 6 months]
Blood samples for serum PK analysis will be obtained (AUC).
- Maximum serum concentration (Cmax) of EMB-06. [Through treatment until EOT visit, expected average 6 months]
Blood samples for serum PK analysis will be obtained (Cmax).
- Trough concentration (Ctrough) of EMB-06. [Through treatment until EOT visit, expected average 6 months]
Blood samples for serum PK analysis will be obtained (Ctrough).
- Average concentration over a dosing interval (Css, avg) of EMB-06. [Through treatment until EOT visit, expected average 6 months]
Blood samples for serum PK analysis will be obtained (Css, avg).
- Terminal half-life (T1/2) of EMB-06. [Through treatment until EOT visit, expected average 6 months]
Blood samples for serum PK analysis will be obtained (T1/2).
- Systemic clearance (CL) of EMB-06. [Through treatment until EOT visit, expected average 6 months]
Blood samples for serum PK analysis will be obtained (CL).
- Steady state volume of distribution (Vss) of EMB-06. [Through treatment until EOT visit, expected average 6 months]
Blood samples for serum PK analysis will be obtained (Vss).
- Progression free survival (PFS) of EMB-06 as assessed by IMWG criteria. [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]
Preliminary anti-multiple myeloma activity of EMB-06 will be obtained (PFS).
- Duration of response of EMB-06 as assessed by IMWG criteria [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]
Preliminary anti-multiple myeloma activity of EMB-06 will be obtained (DOR).
- Incidence and titer of anti-drug antibodies stimulated by EMB-06. [Up to End of Treatment Follow Up Period (30 days after the last dose)]
Antibodies to EMB-06 will be assessed to evaluate potential immunogenicity.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Willing and able to provide written informed consent.
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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.
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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.
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ECOG performance status 0 or 1 for phase I, and ≤2 for phase II.
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Adequate organ function and reasonable laboratory test results to participate in the trial.
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Highly effective contraception
Exclusion Criteria:
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Life expectancy is less than 3 months.
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Patient participated in any other clinical study within 1 month prior to enrollment in this clinical study.
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Patients with ongoing AE.
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Previously treated with any BCMA-targeted therapy.(Exception: in Phase 2 portion, partial patients who have received prior anti-BCMA ADC or BCMA targeted CAR-T can be enrolled)
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History of allogeneic stem cell transplantation.
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Previously treated with the following anti-tumor therapy (prior to first dosing of EMB-06)
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Treated with monoclonal antibody for multiple myeloma within 28 days
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Treated with proteasome inhibitors within 14 days
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Treated with immunomodulatory agents within 14 days
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Treated with cytotoxic therapy within 14 days
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Received investigational drug within 28 days or at least 5 half-lives, whichever is shorter (if a, b, c, d not applicable)
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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
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Plasmapheresis within 7 days
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Patient received autologous stem cell transplantation within 12 weeks prior to the start of study treatment.
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Active or historically multiple myeloma related central nervous system involvement.
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Patients requiring high dose of systemic treatment with corticosteroids.
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Patients with active infections, including COVID-19, hepatitis, etc..
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History of severe allergic reactions
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Patients with severe or uncontrolled cardiovascular disorder requiring treatment
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Pre-existing other serious medical conditions
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Sunshine Coast Haematology and Oncology Clinic (SCHOC) | Buderim | Queensland | Australia | 4556 |
| 2 | Cabrini Health | Melbourne | Victoria | Australia | |
| 3 | Epworth Healthcare | Richmond | Victoria | Australia | 3121 |
| 4 | One Clinical Research (OCR) | Nedlands | Western Australia | Australia | 6009 |
| 5 | Beijing Jishuitan Hospital | Beijing | Beijing | China | 100035 |
| 6 | Ruijin Hospital, Shanghai Jiaotong University School of Medicine | Shanghai | Shanghai | China | 200020 |
Sponsors and Collaborators
- Shanghai EpimAb Biotherapeutics Co., Ltd.
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- EMB06X101