Mezigdomide and Elranatamab for Relapsed and/or Refractory Multiple Myeloma

NCT06645678 | Recruiting Phase 1 DMC

• 1 other identifier: H-2410-028-1576
• Study Type: interventional
• Target: 75
• Locations: 2 countries
• Sites: 7

Brief Summary

The goal of this clinical trial is to find out how well a combination of two medicines (mezigdomide and elranatamab) works in treating patients with refractory/relapsed multiple myeloma.

Conditions

Relapsed Refractory Multiple Myeloma (RRMM)

Keywords

R/R MM; Elranatamab; Mezigdomide

Outcome Measures

Primary Outcomes (1)

• Overall response rate (ORR)

  Percentage of subjects who achieve best response of partial response (PR) or better according to the IMWG Uniform Response Criteria for Multiple Myeloma

  From C1D1 to confirmed PD, lost to follow-up, or death (whichever occurs first), assessed up to 24 months

Secondary Outcomes (10)

• Progression-free survival (PFS)

  From randomization to first documentation of progressive disease or death due to any cause, assessed up to 24 months.

• Overall survival (OS)

  Time from randomization to time of death due to any cause, assessed up to 24 months.

• Complete Response Rate (CR) or better

  From C1D1 to confirmed PD, lost to follow-up, or death (whichever occurs first), assessed up to 24 months

• Very Good Partial Response Rate (VGPR) or better

  From C1D1 to confirmed PD, lost to follow-up, or death (whichever occurs first), assessed up to 24 months

• Time to Response (TTR)

  Time from randomization to the first documentation of response (PR or better), assessed up to 24 months.

Other Outcomes (1)

• Biomarkers

  From C1D1 to End of trial, assessed up to 24 months.

Study Arms (1)

Treatment arm

EXPERIMENTAL

Participants will receive elranatamab, mezigdomide and dexamethasone. Part 1 (safety cohort): approximately 12 participants to select the optimal RP2D and to assess the safety, tolerability, and preliminary efficacy. Every cycle consists of 28 days. Part 2 (expansion cohort): approximately 63 participants will be enrolled. The primary objective of Part 2 is to determine the overall response rate per IMWG criteria at 24 months after enrollment.

Drug: Elranatamab; Drug: Mezigdomide; Drug: Dexamethasone

Interventions

Elranatamab DRUG

Elranatamab: Participants will receive SC administration of elranatamab QW or Q2W. The initial doses of elranatamab will be 12mg (C0D1), 32mg (C0D4), and 76mg (C0D8) and will serve as the 2 step-up priming regimen (Cycle 0). Then, 76mg weekly C1-C6 \> then 76mg bi-weekly from C7 for those achieving PR or better \> then 76mg q4weeks from C12 for those achieving CR or better response. If the participant subsequently begins to have an increase of disease burden not yet qualifying as PD according to IMWG criteria, dose intervals will return to weekly dosing. premedication for Elranatamab: Acetaminophen 650mg (or paracetamol 500mg), Diphenhydramine 25mg (or equivalent), Dexamethasone 20mg (or equivalent). In case of mezigdomide discontinuation due to reasons other than disease progression, elranatamab continuation +/- dexamethasone will be allowed until loss of response. The administration of elranatamab +/- dexamethasone will continue per study protocol schedule.

Treatment arm

Mezigdomide DRUG

The first day of study treatment dosing with mezigdomide is considered Day 1 of a cycle. (per recommended phase 2 dose, daily \[qd\], D1-21, q 4weeks). Capsules of mezigdomide will be taken by mouth with or without food. In case of elranatamab discontinuation due to reasons other than disease progression, mezigdomide continuation +/- dexamethasone will be allowed until loss of response. The administration of mezigdomide will continue per study protocol.

Treatment arm

Dexamethasone DRUG

Administered at the dose of 20 mg/day from C1-3, then 10mg/day from C4-6 as a premedication for elranatamab. (for those \>=75 yrs, with uncontrolled diabetes mellitus, history of intolerance: 10mg/day -\> 5mg/day)

Treatment arm

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must satisfy the following criteria to be enrolled in the study:
• Subject is ≥ 19 years of age at the time of signing the informed consent form (ICF).
• ② Subject must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted.
• Subject is willing and able to adhere to the study visit schedule and other protocol requirements.
• ④ Subject has documented diagnosis of MM and measurable disease, defined as any of the following: A. M-protein ≥ 0.5 g/dL by serum protein electrophoresis (sPEP) or B. M-protein ≥ 200 mg/24-hour urine collection by urine protein electrophoresis (uPEP) or C. For subjects without measurable disease in sPEP or uPEP: serum free light chain (sFLC) levels \> 100 mg/L (10 mg/dL) involved light chain and an abnormal kappa/lambda FLC ratio.
• \*Patients with measurable disease and extramedullary disease will be allowed to participate if there is a measurable extramedullary lesion. These patients require PET-CT follow-up for response evaluation. Those with extramedullary disease (EMD) only will not be allowed to participate: i.e, Patients with plasmacytoma as the only measurable disease are not eligible. For the definition of EMD, refer to Section 8.1.3.
• ⑤ Subject has received 2 or more prior lines of antimyeloma therapy. (Note: One line can contain several phases \[e.g., induction, (with or without) hematopoietic stem cell transplant, (with or without) consolidation, and/or (with or without) maintenance therapy).
• ⑥ Subject must have received at least one proteasome inhibitor and lenalidomide.
• ⑦ Subject achieved minimal response or better to at least 1 prior antimyeloma therapy.
• Subject must have documented disease progression during or after their last antimyeloma regimen.
• ⑨ Subject has an Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1 or 2.
• ⑩ Individual of childbearing potential (IOCBP) must: A. Have two negative pregnancy tests as verified by the Investigator prior to starting study treatment. She must agree to ongoing pregnancy testing during the course of the study, and after the end of study treatment. This applies even if the subject practices true abstinence\* from heterosexual contact.
• B. Either commit to true abstinence\* from heterosexual contact (which must be reviewed on a monthly basis and source documented) or agree to use, and be able to comply with, 2 forms of contraception: one highly effective, and one additional effective (barrier) measure of contraception without interruption 28 days prior to starting study treatment, during the study treatment (including dose interruptions), and for at least 28 days after the last dose of mezigdomide or 150 days after the last dose of elranatamab, whichever is longer.
• Note: A IOCBP (Individual of childbearing potential): an individual who: 1) has achieved menarche (first menstrual cycle) at some point; 2) has not undergone a hysterectomy (the surgical removal of the uterus) or bilateral salpingectomy (the surgical removal of the fallopian tubes) or oophorectomy (the surgical removal of both ovaries) or 3) has not been naturally postmenopausal (without an alternative medical cause eg, amenorrhea following cancer therapy does not rule out childbearing potential) for at least 12 consecutive months (ie, has had menses at any time during the preceding 12 consecutive months).
• ⑪ Male subjects must: A. Practice true abstinence\* (which must be reviewed on a monthly basis) or agree to use a condom during sexual contact with a pregnant individual or an individual of childbearing potential while participating in the study, during dose interruptions and for at least 28 days after the last dose of mezigdomide whichever is longer, even if he has undergone a successful vasectomy.

You may not qualify if:

• Subject who has had prior treatment with mezigdomide. 2 Patients with gastrointestinal disease or surgery (eg, gastric bypass surgery) that may significantly alter the absorption of mezigdomide and/or other oral study intervention.
• Subject who has had prior treatment with anti-BCMA agents (including CAR T-cell therapy, bispecifics and antibodies).
• Subject who has had any investigational agents within 28 days or 5 half-lives (whichever is shorter) of initiating study treatment.
• A. Participation in another interventional clinical trial concurrent with this study is not permitted, except for those who have completed treatment with the prior investigational agent(s) and are currently in Long-term Follow up.
• Subject has received any of the following. A. Plasmapheresis within the last 28 days of initiating study treatment B. Major surgery (as defined by the Investigator) within 28 days of initiating study treatment.
• C. Radiation therapy, other than local palliative therapy, for myeloma associated bone lesions within 14 days of initiating study treatment.
• D. Use of any systemic antimyeloma drug therapy within 14 days of initiating study treatment.
• E. Use of potassium competitive acid blockers (eg. tegoprazan, vonoprazan) within 7 days of initiating study treatment.
• Subject has previously received allogeneic stem cell transplantation within a year during prior therapy or received autologous stem cell transplantation within 12 weeks of initiating study treatment. Patients who received allogeneic stem cell transplantation should not have evidence of active GVHD.
• Subject has plasma cell leukemia defined by IMWG definition for primary plasma cell leukemia, Waldenstrom's macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes) or clinically significant light-chain amyloidosis.
• Subject with known central nervous system (CNS) involvement with myeloma. 9 Subject has any significant medical condition, including active or uncontrolled infection, presence of laboratory abnormality, or psychiatric illness that places the subject at an unacceptable risk for treatment-related complications, if he/she were to participate in the study.
• Coronavirus disease 2019 (COVID-19) within 7 days for mild or asymptomatic infections or 14 days for moderate/severe infections prior to initiating study intervention. A longer duration may be needed based on the investigator's clinical judgment.
• i) Acute symptoms must have resolved and there are no sequelae that would place the participant at a higher risk of receiving study intervention, based on investigator Assessment. No repeat/follow-up COVID-19 testing is required
• Subject has any condition that confounds the ability to interpret data from the study.
• Subject has any of the following laboratory abnormalities: A. Absolute neutrophil count (ANC) \< 1,000/µL. It is not permissible to administer GCSF to achieve minimum ANC levels within 7 days prior to screening complete blood count (CBC) (or within 14 days prior for pegfilgrastim).\* B. Platelet count: \< 75,000/µL for subjects in whom \< 50% of bone marrow nucleated cells are plasma cells; or a platelet count \< 50,000/µL for subjects in whom ≥ 50% of bone marrow nucleated cells are plasma cells (transfusions are not permitted within 7 days prior to screening CBC).\* C. Hemoglobin \< 8 g/dL (\< 4.9 mmol/L).\*

Sponsors & Collaborators

• YOUNGIL KOH: lead

Study Sites (7)

National University Hospital (NUH)

Singapore, Singapore

RECRUITING

Singhealth Duke NUS blood cancer center

Singapore, Singapore

RECRUITING

Chonnam National University Hwasun Hospital

Hwasun, South Korea

RECRUITING

Asan Medical Center, University of Ulsan College of Medicine

Seoul, South Korea

RECRUITING

Samsung Medical Center, Sungkyunkwan University School of Medicine

Seoul, South Korea

RECRUITING

Seoul National University Hospital

Seoul, South Korea

NOT YET RECRUITING

Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea

Seoul, South Korea

RECRUITING

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Dexamethasone

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

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Central Study Contacts

Youngil Koh, MD, PhD

CONTACT

82-02-2072-7217; go01@snu.ac.kr

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor, MD PhD

Model Details: Elranatamab: C0D1 12mg sc, C0D4 32mg sc, C0D8 76mg sc, then 76mg sc weekly C1-C6, then 76mg sc bi-weekly from C7 for those achieving PR or better response, then 76mg sc q 4weeks from C12 for those achieving CR or better response Mezigdomide: per RP2D qd, D1-21, q 4weeks Dexamethasone: with elranatamab up until C6: 20mg/day C1-3 \> 10mg/day D4-6 (for those \>= 75 years old, with uncontrolled DM, Hx of intolerance, 10mg/day -\> 5mg/day) 28days/cycle, 24 cycles (2 years) fixed duration.

Study Record Dates

• First Submitted: October 14, 2024
• First Posted: October 17, 2024
• Study Start: November 26, 2024
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): October 1, 2027
• Last Updated: December 3, 2025

Record last verified: 2025-11

Locations

KR (5); SG (2)