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

Relapsed or Refractory Multiple Myeloma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04735575
• Other study ID #: EMB06X101
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: May 20, 2021
• Est. completion date: March 1, 2025

Study information

• Verified date: August 2023
• Source: Shanghai EpimAb Biotherapeutics Co., Ltd.
• Contact: Shuqi Zeng
• Phone: +8618621781427
• Email: shqzeng[@]epimab.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 66
• Est. completion date: March 1, 2025
• Est. primary completion date: December 1, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

1. Treated with monoclonal antibody for multiple myeloma within 28 days

2. Treated with proteasome inhibitors within 14 days

3. Treated with immunomodulatory agents within 14 days

4. Treated with cytotoxic therapy within 14 days

5. Received investigational drug within 28 days or at least 5 half-lives, whichever is shorter (if a, b, c, d not applicable)

6. 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

7. 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

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell
• Relapsed or Refractory Multiple Myeloma

Intervention

Biological:
• EMB-06
EMB-06 is a FIT-Ig® bispecific antibody against BCMA and CD3.

Locations

Country	Name	City	State
Australia	Sunshine Coast Haematology and Oncology Clinic (SCHOC)	Buderim	Queensland
Australia	Cabrini Health	Melbourne	Victoria
Australia	One Clinical Research (OCR)	Nedlands	Western Australia
Australia	Epworth Healthcare	Richmond	Victoria
China	Beijing Jishuitan Hospital	Beijing	Beijing
China	Peking University, Third Hospital	Beijing
China	Guangdong Provincial People's Hospital	Guangzhou
China	The First Affiliated Hospital of Zhejiang University School of Medicine	Hangzhou
China	Ruijin Hospital, Shanghai Jiaotong University School of Medicine	Shanghai	Shanghai
China	Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology	Wuhan
China	Henan Cancer Hospital	Zhengzhou

Sponsors (1)

Lead Sponsor	Collaborator
Shanghai EpimAb Biotherapeutics Co., Ltd.

Countries where clinical trial is conducted

Australia,  China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence and severity of adverse events	Incidence and severity of AE.	Screening up to follow-up (30 days after the last dose)
Primary	Incidence of serious adverse events (SAE)	Incidence of SAE	Screening up to follow-up (30 days after the last dose)
Primary	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)
Primary	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)
Primary	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)
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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)