A Study of the Safety, Tolerability and Effectiveness of EZM0414 (IPN60210) Investigative Product in Participants With Relapsed/Refractory Multiple Myeloma and Relapsed/Refractory Diffuse Large B Cell Lymphoma

NCT05121103 | Terminated Phase 1 Results FDA Drug

• 1 other identifier: SET-101
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 8

Brief Summary

This study will include participants with relapsed/refractory (R/R) Multiple Myeloma (MM). MM is a type of cancer of the blood. This study will also include participants with relapsed/refractory (R/R) Diffuse Large B-Cell Lymphoma (DLBCL). DLBCL is also a type of cancer of the blood. They are referred to as 'relapsed' when the disease has come back after treatment and 'refractory' when treatment no longer works. The study has 2 main parts, called phase 1 and phase 1b. The main objective of both parts will be to evaluate the safety and tolerability of the study drug, called EZM0414. The main objective of phase 1b will also be to determine the effectiveness of EZM0414. During phase 1 six dose levels will be tested to obtain the most tolerated dose. Participants will receive study drug at the assigned dose level every 28 days. During phase 1b participants will receive study drug at the maximum tolerated dose in 28-day cycles.

Conditions

Multiple Myeloma, Refractory; Diffuse Large B-Cell Lymphoma; Diffuse Large B Cell Lymphoma Refractory; Multiple Myeloma in Relapse

Outcome Measures

Primary Outcomes (3)

• Part 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)

  An adverse event was any untoward medical occurrence in a participant or clinical investigation participant administered a medicinal product and which does not necessarily had a causal relationship with this treatment. A serious adverse event was any untoward medical occurrence that at any dose, resulted in death, was life-threatening, required in-subject hospitalization or prolongation of hospitalization, resulted in persistent or significant disability or incapacity, or resulted in a congenital abnormality or birth defect, was an important medical event. A TEAE was an AE that started or worsened in severity on or after the date of the first dose of the study treatment through 30 days after the end of treatment.

  From first dose of study treatment (Day 1) up to 30 days after the last dose of study treatment (Day 57), up to approximately 87 days

• Part 1: Number of Participants With Dose-limiting Toxicities (DLTs)

  According to National Cancer Institute's Common Terminology Criteria for Adverse Events version 5.0, DLT was defined as any of following AE that occurred in Part 1 during first cycle of study treatment: grade (G)4 neutropenia lasting \>5 days; G3 febrile neutropenia; G3 thrombocytopenia with clinically significant bleeding; G4 thrombocytopenia; G4 anemia unexplained by underlying disease; any other non-hematological toxicity ≥3 except: alopecia, G3 nausea/vomiting or diarrhea for \<3 days with supportive care, G3 fatigue for \<1 week, G3 or higher isolated electrolyte abnormalities for up to 3 days, not clinically complicated, and resolved spontaneously, or responded to conventional medical interventions; G3 or higher amylase/lipase elevation without symptoms of pancreatitis; G3 tumor lysis syndrome for up to 3 days, not clinically complicated, and resolved spontaneously, or responded to conventional medical interventions; and any participant meeting Hy's law criteria.

  From first dose of study treatment (Cycle 1 Day 1) up to end of the Cycle 1 (Cycle 1 Day 28), maximum of 28 days

• Part 2: Objective Response Rate (ORR)

  ORR was planned to be assessed in Part 2. ORR was defined as percentage of responders as assessed by Investigator per International Myeloma Working Group (IMWG) 2016 guidelines for MM (complete response \[CR\], stringent CR \[sCR\], partial response \[PR\], very good PR \[VGPR\]) or Lugano 2014 guidelines for DLBCL (CR+PR). Per IMWG response criteria, CR: negative immunofixation on serum and urine; disappearance of soft tissue plasmacytomas; \<5% plasma cells in bone marrow(BM); sCR: CR + normal free light chain (FLC) ratio; absence of BM clonal cells by immunohistochemistry; VGPR: serum and urine M-protein (MP) detected by immunofixation but not on electrophoresis or ≥90% reduction in serum MP + urine MP\<100 mg/24 hours (h) or ≥90% decrease in sum of maximal perpendicular diameter (SPD) compared to baseline in soft tissue plasmacytoma; PR: ≥50% reduction of serum MP and reduction in 24 h urinary M-protein by ≥90% or to \<200 mg/24 h; ≥50% reduction in size (SPD) of soft tissue plasmacytomas.

  Tumour assessments were planned to be performed at Screening (within 28 days before start of study treatment) or Cycle 1 Day 1 (pre-dose) up to end of the study, approximately 23 months

Secondary Outcomes (3)

• Part 2: Progression-free Survival (PFS)

  Tumour assessments were planned to be performed at Screening (within 28 days before start of study treatment) or Cycle 1 Day 1 (pre-dose) up to end of the study, approximately 23 months

• Part 2: Disease Control Rate (DCR)

  Tumour assessments were planned to be performed at Screening (within 28 days before start of study treatment) or Cycle 1 Day 1 (pre-dose) up to end of the study, approximately 23 months

• Part 2: Duration of Response (DOR)

  Tumour assessments were planned to be performed at Screening (within 28 days before start of study treatment) or Cycle 1 Day 1 (pre-dose) up to end of the study, approximately 23 months

Study Arms (1)

Open-label EZM0414

EXPERIMENTAL

Participants will receive EZM0414 in continuous 28-day cycles. EZM0414 will be administered orally once daily (QD) without food. Participants who receive EZM0414 at Maximum tolerated dose (MTD) and do not have Dose limiting toxicities (DLT) in the dose escalation part of the study will be rolled over to a cohort of this dose expansion part. Cohort 1 for R/R MM Participants. Cohort 2 for R/R MM Participants. Cohort 3 for Participants with R/R DLBCL.

Drug: EZM0414

Interventions

EZM0414 DRUG

Immediate-release film-coated tablets: Six dose levels starting at 100 mg, and then 200 mg, 300 mg, 400 mg, 600 mg, and 900 mg as well as an optional step-down dose level of 75 mg (if needed)

Also known as: IPN60210

Open-label EZM0414

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Subjects must be ≥18 years of age at the time of signing the ICF (Informed Consent Form).
• Subjects must have an Eastern Cooperative Oncology Group (ECOG) status of 0 - 2.
• For MM, subjects must have measurable disease by IMWG (International Myeloma Working Group) 2016 criteria
• For DLBCL, subjects must have measurable disease by Lugano criteria
• Females must not be breastfeeding or pregnant at screening
• Females of childbearing potential must not have had unprotected sexual intercourse while participating in this study
• Male subjects must either practice complete abstinence or agree to use a latex or synthetic condom, even with a successful vasectomy, during study treatment and for 30 days after the final dose of study treatment

You may not qualify if:

• Subjects with plasma cell leukemia defined as a plasma cell count \>2000/mm3.
• Subjects with Waldenstrom's macroglobulinemia or smoldering MM.
• Subjects who had prior treatment with SETD2 or NSD2 inhibitor.
• Subjects with active acute or chronic systemic infection requiring systemic treatment, including COVID-19.
• Has cardiovascular impairment
• Prolongation of corrected QT interval using Fridericia's formula (QTcF) to \> 480 msec or history of long QT syndrome.
• Known left ventricular ejection fraction (LVEF) \< 50% by either echocardiogram (ECHO) or multigated acquisition (MUGA).
• Prior major surgery within 4 weeks of treatment start.
• Known hypersensitivity to components of the investigational product.
• Subjects who have received treatment with any unapproved drug product within 4 weeks prior to screening.
• Current participation in any other interventional clinical study except for follow up.
• Subjects with a history of or active malignancy other than disease under study
• 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.
• 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

Sponsors & Collaborators

• Epizyme, Inc.: lead

Study Sites (8)

City of Hope

Duarte, California, 91010, United States

Location

Astera Cancer Care

East Brunswick, New Jersey, 08816, United States

Location

Weill Cornell Medicine

New York, New York, 10021, United States

Location

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

Baylor University Medical Center (Texas Oncology)

Dallas, Texas, 75246, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

NEXT Virginia

Fairfax, Virginia, 22031, United States

Location

Related Links

• Lay language results summary

MeSH Terms

Conditions

Multiple Myeloma; Lymphoma, Large B-Cell, Diffuse

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Lymphatic Diseases

Limitations and Caveats

This study was terminated prior to completing Part 1 due to business reasons. Study termination was not due to safety concerns.

Results Point of Contact

• Title: Medical Director
• Organization: Ipsen

clinical.trials@ipsen.com

see email

Study Officials

• Ipsen Medical Director

  Ipsen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 18, 2021
• First Posted: November 16, 2021
• Study Start: May 31, 2022
• Primary Completion: April 30, 2024
• Study Completion: April 30, 2024
• Last Updated: June 22, 2025
• Results First Posted: May 11, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (8)