Clinical trial NCT05121103: 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
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Multiple Myeloma, Refractory
Diffuse Large B-Cell Lymphoma
Diffuse Large B Cell Lymphoma Refractory
Multiple Myeloma in Relapse
Lead sponsor: Ipsen
Sponsor class: INDUSTRY
First posted: 2021-11-16
Enrollment: 13
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Detailed description: The first part of the study will be a Phase 1 dose-escalation designed to evaluate the safety, tolerability, and pharmacokinetics (PK) of EZM0414 in subjects with R/R MM and R/R DLBCL.

Six dose levels starting at 100 mg, then 200 mg, 300 mg, 400 mg, 600 mg, and 900 mg as well as an optional step-down dose of 75 mg (if needed) 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.

Eligibility criteria: 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 (ECOG) status of 0 - 2.
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 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

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

Primary outcomes:
measure: Part 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)
timeFrame: 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
measure: Part 1: Number of Participants With Dose-limiting Toxicities (DLTs)
timeFrame: 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
measure: Part 2: Objective Response Rate (ORR)
timeFrame: 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:
measure: Part 2: Progression-free Survival (PFS)
timeFrame: 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
measure: Part 2: Disease Control Rate (DCR)
timeFrame: 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
measure: Part 2: Duration of Response (DOR)
timeFrame: 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
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope
state: California
city: East Brunswick
country: United States
facility: Astera Cancer Care
state: New Jersey
city: New York
country: United States
facility: Weill Cornell Medicine
state: New York
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: Dallas
country: United States
facility: Baylor University Medical Center (Texas Oncology)
state: Texas
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Fairfax
country: United States
facility: NEXT Virginia
state: Virginia
Study officials:
affiliation: Ipsen
name: Ipsen Medical Director
role: STUDY_DIRECTOR
References: