Clinical trial NCT04735575: A Ph1/2 Study of EMB-06 in Participants With Relapsed or Refractory Myeloma
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Relapsed or Refractory Multiple Myeloma
Keywords: Phase I/II
Bispecific antibody
BCMA
CD3
EMB-06
Immuno-oncology
Dose escalation
Cohort expansion
Relapsed or Refractory Multiple Myeloma
Hematological malignancy
Lead sponsor: Shanghai EpimAb Biotherapeutics Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2021-02-03
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Dose escalation followed by Cohort Expansion Phase at the RP2D.
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Incidence and severity of adverse events
timeFrame: Screening up to follow-up (30 days after the last dose)
measure: Incidence of serious adverse events (SAE)
timeFrame: Screening up to follow-up (30 days after the last dose)
measure: Incidence of dose interruptions.
timeFrame: Screening up to follow-up (30 days after the last dose)
measure: Dose intensity
timeFrame: Screening up to follow-up (30 days after the last dose)
measure: The incidence of DLTs during treatment.
timeFrame: First infusion to the end of Cycle 1 (each cycle is 28 days)
measure: Overall Response Rate (ORR)
timeFrame: 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 outcomes:
measure: Area under the serum concentration-time curve (AUC) of EMB-06.
timeFrame: Through treatment until EOT visit, expected average 6 months
measure: Maximum serum concentration (Cmax) of EMB-06.
timeFrame: Through treatment until EOT visit, expected average 6 months
measure: Trough concentration (Ctrough) of EMB-06.
timeFrame: Through treatment until EOT visit, expected average 6 months
measure: Average concentration over a dosing interval (Css, avg) of EMB-06.
timeFrame: Through treatment until EOT visit, expected average 6 months
measure: Terminal half-life (T1/2) of EMB-06.
timeFrame: Through treatment until EOT visit, expected average 6 months
measure: Systemic clearance (CL) of EMB-06.
timeFrame: Through treatment until EOT visit, expected average 6 months
measure: Steady state volume of distribution (Vss) of EMB-06.
timeFrame: Through treatment until EOT visit, expected average 6 months
measure: Progression free survival (PFS) of EMB-06 as assessed by IMWG criteria.
timeFrame: 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
measure: Duration of response of EMB-06 as assessed by IMWG criteria
timeFrame: 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
measure: Incidence and titer of anti-drug antibodies stimulated by EMB-06.
timeFrame: Up to End of Treatment Follow Up Period (30 days after the last dose)
Other outcomes:
Locations:
city: Buderim
country: Australia
facility: Sunshine Coast Haematology and Oncology Clinic (SCHOC)
state: Queensland
city: Richmond
country: Australia
facility: Epworth Healthcare
state: Victoria
city: Nedlands
country: Australia
facility: One Clinical Research (OCR)
state: Western Australia
city: Beijing
country: China
facility: Beijing Jishuitan Hospital
state: Beijing
city: Shanghai
country: China
facility: Ruijin Hospital, Shanghai Jiaotong University School of Medicine
state: Shanghai
city: Beijing
country: China
facility: Peking University, Third Hospital
city: Guangzhou
country: China
facility: Guangdong Provincial People's Hospital
city: Hangzhou
country: China
facility: The First Affiliated Hospital of Zhejiang University School of Medicine
city: Wuhan
country: China
facility: Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
Study officials:
References: