A Study in Subjects With Relapsed/Refractory Multiple Myeloma and Relapsed/Refractory Diffuse Large B-Cell Lymphoma

Sponsor
Epizyme, Inc. (Industry)
Overall Status
Not yet recruiting
CT.gov ID
NCT05121103
Collaborator
(none)
96
Enrollment
3
Locations
1
Arm
41.9
Anticipated Duration (Months)
32
Patients Per Site
0.8
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a first-in-human (FIH), 2-part, open-label, multi-center, Phase 1/1b safety, tolerability, pharmacokinetics (PK), and efficacy study of oral SETD2 inhibitor, EZM0414, in subjects with relapsed/refractory (R/R) Multiple Myeloma (MM) and R/R Diffuse Large B-Cell Lymphoma (DLBCL).

Detailed Description

The first part of the study will be a Phase 1 dose-escalation study designed to evaluate the safety, tolerability, and PK of EZM0414 in subjects with R/R MM and R/R DLBCL. Six dose levels of 100 mg, 200 mg, 300 mg, 400 mg, 600 mg, and 900 mg will be tested. The second part of the study is the Phase 1b dose expansion at the MTD designed to evaluate safety and efficacy in subjects with R/R DLBCL and R/R MM with or without select genetic translocation. Dose expansion will enroll subjects in 3 cohorts: Cohort 1 for R/R MM subjects with t(4;14), cohort 2 for R/R MM subjects without t(4;14), and Cohort 3 for subjects with R/R DLBCL.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
96 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 1/1b, Open-Label, Multi-Center, Two-Part Study of SETD2 Inhibitor EZM0414 in Subjects With Relapsed/Refractory Multiple Myeloma and Relapsed/Refractory Diffuse Large B-Cell Lymphoma
Anticipated Study Start Date :
Dec 31, 2021
Anticipated Primary Completion Date :
Dec 30, 2024
Anticipated Study Completion Date :
Jun 27, 2025

Arms and Interventions

ArmIntervention/Treatment
Experimental: Open-label EZM0414

Drug: EZM0414
Formulation: 25 mg and 200 mg immediate-release film-coated tablets

Outcome Measures

Primary Outcome Measures

  1. Number of participants with treatment-emergent adverse events as assessed by CTCAE v5.0 [Through study completion, an average of 3 years]

    Severity of adverse events experienced by all subjects with at least 1 dose or partial dose of EZM0414 and DLT (Dose Limiting Toxicity) will be evaluated by the Investigator based on the CTCAE, version 5.0

  2. Establishing Maximum Tolerated Dose (MTD) and a recommended Phase 2 Dose (RP2D) [Through study completion, an average of 3 years]

    Determine MTD and select a dose for further evaluation in phase 2 (RP2D)

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
  1. Voluntarily provide signed informed consent after review of verbal and written material about the trial and agree to abide with protocol requirements. All study related activities must be carried out after written consent is obtained.

  2. Subjects must be ≥18 years of age at the time of signing the ICF (Informed Consent Form).

  3. Subjects must have an Eastern Cooperative Oncology Group status of 0 or 1.

  4. For MM, subjects must have measurable disease by IMWG (International Myeloma Working Group) 2016 criteria

  5. For DLBCL, subjects must have measurable disease by Lugano criteria

  6. Females must not be breastfeeding or pregnant at screening

  7. Females of childbearing potential must not have had unprotected sexual intercourse while participating in this study

  8. Male subjects must have had either a successful vasectomy OR they and their female partner must meet the criteria above ie, not of childbearing potential OR practicing highly effective contraception and use a condom throughout the study period

Exclusion Criteria:
  1. Subjects with plasma cell leukemia defined as a plasma cell count >2000/mm3.

  2. Subjects with Waldenstrom's macroglobulinemia or smoldering MM.

  3. Subjects who had prior treatment with SETD2 or NSD2 inhibitor.

  4. Subjects with active acute or chronic systemic infection requiring systemic treatment, including COVID-19.

  5. Has cardiovascular impairment

  6. Prolongation of corrected QT interval using Fridericia's formula (QTcF) to > 480 msec or history of long QT syndrome.

  7. Known left ventricular ejection fraction (LVEF) < 50% by either echocardiogram (ECHO) or multigated acquisition (MUGA).

  8. Prior major surgery within 4 weeks of treatment start.

  9. Known hypersensitivity to components of the investigational product.

  10. Subjects who have received treatment with any unapproved drug product within 4 weeks prior to screening.

  11. Current participation in any other interventional clinical study except for follow up.

  12. Subjects with a history of or active malignancy other than disease under study

  13. Underlying medical/social conditions that in PI opinion will place the subject in significant risk and affect the interpretation of toxicity and adverse events assessments.

  14. Inability to take oral medication or known gastrointestinal (GI) disease, GI procedure or medical condition that could interfere with the oral absorption or tolerance of the study drug

Contacts and Locations

Locations

SiteCityStateCountryPostal Code
1Dana-Farber Cancer InstituteBostonMassachusettsUnited States02215
2Weill Cornell MedicineNew YorkNew YorkUnited States10021
3MD Anderson Cancer CenterHoustonTexasUnited States77030

Sponsors and Collaborators

  • Epizyme, Inc.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Epizyme, Inc.
ClinicalTrials.gov Identifier:
NCT05121103
Other Study ID Numbers:
  • SET-101
First Posted:
Nov 16, 2021
Last Update Posted:
Dec 17, 2021
Last Verified:
Dec 1, 2021
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:

Study Results

No Results Posted as of Dec 17, 2021