Mezigdomide and Talquetamab in Relapsed and Refractory Multiple Myeloma

NCT07032714 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 25-320
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 3

Brief Summary

This is a phase 1 study to find the recommended dose and schedule of mezigdomide and talquetamab in relapsed and refractory multiple myeloma (RRMM), and to test the effects of the drugs on cancer. Cohort A will receive talquetamab + dexamethasone, then mezigdomide + talquetamab,+ dexamethasone. After Cohort A, Cohort B will evaluate mezigdomide + dexamethasone followed by step-up dosing of talquetamab (mezigdomide + talquetamab,+ dexamethasone).

Conditions

Relapsed Refractory Multiple Myeloma (RRMM)

Keywords

Relapsed Refractory Multiple Myeloma (RRMM); Prior therapy; Triple class exposed RRMM

Outcome Measures

Primary Outcomes (1)

• Recommended Dose

  To determine the recommended dose and schedule of mezigdomide and talquetamab in triple class exposed, relapsed and refractory multiple myeloma (RRMM), the dose level where 2 of 6 participants experience a DLT is considered the maximum tolerated dose. The dose level below this will be considered a recommended phase 2 dose. Or if dose level 2 is reached (mezigdomide 1 mg po for 21 out of 28 days) and there are ≤1 DLTs out of 6 participants, then dose level 2 will be considered the recommended phase 2 dose. Data from the secondary outcomes (frequency of adverse events, serious adverse events, and dose-limiting toxicities) will be used for this outcome.

  Day 1 of treatment through 30 days post last-dose (treatment is until disease progression or withdrawal; estimated to be 1 year from Day 1 of treatment)

Secondary Outcomes (6)

• Frequency of adverse events

  Day 1 of treatment through 30 days post last-dose (treatment is until disease progression or withdrawal; estimated to be 1 year from Day 1 of treatment)

• Frequency of serious adverse events

  Day 1 of treatment through 30 days post last-dose (treatment is until disease progression or withdrawal; estimated to be 1 year from Day 1 of treatment)

• Frequency of dose-limiting toxicities (DLT)

  Day 1 of treatment through 30 days post last-dose (treatment is until disease progression or withdrawal; estimated to be 1 year from Day 1 of treatment)

• Overall response rate (ORR)

  Day 1 of treatment through 2 years post last-dose (estimated total time to be 3 years; treatment is until disease progression or withdrawal)

• Progression Free Survival (PFS)

  Day 1 of treatment through 2 years post last-dose (estimated total time to be 3 years; treatment is until disease progression or withdrawal)

Study Arms (2)

Cohort A

EXPERIMENTAL

Cycle 1: Talquetamab and dexamethasone at a pre-determined escalating dose of talquetamab. Talquetamab is subcutaneously injected on Day 1, 4, 8, and 15 of the 28-day cycle. Dexamethasone is administered orally before receiving talquetamab (Days 1, 4, 8, 15). Cycle 2+: Mezigdomide, talquetamab, and dexamethasone Talquetamab is administered on Day 1 and 15 of cycles 2-6 and on Day 1 of cycles 7-12. Mezigdomide is administered orally once per day on days 1-21 of each 28-day cycle starting with cycle 2. This can continue until disease progression or withdrawal. Dexamethasone is administered orally once per week starting on Day 1 of Cycle 2 through cycle 6; the weekly dose will be split into 2 days.

Drug: Talquetamab; Drug: Mezigdomide; Drug: Dexamethasone

Cohort B

EXPERIMENTAL

Cohort B takes place after Cohort A. Pre-phase 7 day cycle: Mezigdomide is administered orally once per day on Days 1-7. Dexamethasone is administered orally on Days 1 and 2. Cycle 1 (28 day cycle): Talquetamab is subcutaneously injected on Day 1, 4, 8, and 15 at a pre-determined escalating dose. Mezigdomide is given orally on days 1-14. Dexamethasone is administered orally as pre-medications before receiving talquetamab. Cycle 2+ (28 day cycle): Talquetamab on Days 1 and 15 of cycles 2-6; then Day 1 of cycles 7-12. Mezigdomide on Days 1-21 of cycles 2+ until disease progression or withdrawal. Dexamethasone on Days 1, 2, 8, 9, 15, 16, 22, 23 of cycles 2-6.

Drug: Talquetamab; Drug: Mezigdomide; Drug: Dexamethasone

Interventions

Talquetamab DRUG

Talquetamab is injected under the skin (subcutaneously injected) by trained medical staff. During first cycle of talquetamab, the dose of talquetamab will increase until the goal dose (treatment dose) is reached (pre-determined dose escalation).

Cohort A; Cohort B

Mezigdomide DRUG

Administered orally once per day (days 1-21 of applicable 28-day cycles; Days 1-7 of the 7-day Cohort B pre-phase cycle).

Cohort A; Cohort B

Dexamethasone DRUG

Administered orally once per day, at the schedule outlined in the Arm Descriptions.

Cohort A; Cohort B

Eligibility Criteria

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

You may qualify if:

• Participant has given voluntary signed written informed consent before performance of any study-related procedure that is not part of normal medical care, with the understanding that consent may be withdrawn by the participant at any time without prejudice to their future medical care.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤2 (see Appendix).
• Age ≥ 18 years
• Measurable disease of multiple myeloma as defined by at least one of the following:
• Serum monoclonal protein ≥ 0.5 g/dL. Patients with IgD disease and lower amounts of monoclonal protein may be permitted to enroll with PI approval
• ≥ 200 mg of monoclonal protein in the urine on 24-hour urine protein electrophoresis
• Serum free light chain (FLC) ≥ 100 mg/L (10 mg/dL) and abnormal serum free light chain ratio
• Previously treated relapsed and refractory multiple myeloma:
• Patients must have received at least three prior lines of therapy;
• Prior therapy including an immunomodulatory drug, proteasome inhibitor, and anti-CD38 antibody (either in separate regimens or within the same regimen); and
• Disease progression on, or within 60 days of completion of last therapy.
• ANC ≥ 1000/μL. G-CSF is not permitted within 14 days of screening.
• Platelet count ≥ 50,000/µL. Platelet transfusion and thrombopoietin receptor agonists are not permitted within 7 days of screening.
• Hemoglobin ≥ 8 g/dL. Red blood cell transfusions are permitted to meet eligibility criteria.
• Calculated creatinine clearance of ≥ 30 mL/min by Modified Diet in Renal Disease (MDRD) formula or Cockcroft-Gault formula

You may not qualify if:

• Participants who have had myeloma therapy or investigational drug within 2 weeks prior to start of treatment or those who have not recovered from adverse events due to agents administered more than 2 weeks earlier.
• Participants who are receiving any investigational agents.
• Prior therapy with mezigdomide or iberdomide.
• Prior therapy with anti-GPRC5D therapy (e.g. talquetamab).
• Prior therapy with bispecific antibody therapy within three months
• Prior therapy with gene-modified adoptive cell therapy (e.g. CAR T-cells, NK cells) within three months
• Plasmapheresis within seven days prior to start of study treatment.
• Primary refractory disease.
• Concomitant high dose corticosteroids. Low dose corticosteroids (maximum dose prednisone 10 mg/day or equivalent) are permitted if given for disorders other than myeloma, e.g. adrenal insufficiency, rheumatoid arthritis, etc.

Sponsors & Collaborators

• Celgene Corporation: collaborator
• Massachusetts General Hospital: lead
• Janssen Research and Development LLC: collaborator

Study Sites (3)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

RECRUITING

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02115, United States

NOT YET RECRUITING

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

NOT YET RECRUITING

MeSH Terms

Conditions

Multiple Myeloma

Interventions

talquetamab; 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

Study Officials

• Andrew J. Yee, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Andrew J. Yee, MD

CONTACT

617-724-4000; ayee1@mgh.harvard.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 16, 2025
• First Posted: June 24, 2025
• Study Start: December 19, 2025
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): July 1, 2028
• Last Updated: April 13, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: Contact the Partners Innovations team at http://www.partners.org/innovation

Locations

US (3)