Mezigdomide and Talquetamab in Relapsed and Refractory Multiple Myeloma

NCT ID: NCT07032714

Last Updated: 2025-06-26

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 25 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-12-16
• Study Completion Date: 2028-07-01

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).

Detailed Description

This phase 1 open-label study will determine the recommended dose and schedule of mezigdomide and talquetamab in triple class exposed relapsed and refractory multiple myeloma. This study aims to enroll 25 participants including Cohorts A and B, and will follow a dose escalation schedule. Treatment is until progression or withdrawal of consent. The U.S. Food and Drug Administration (FDA) has not approved the combination of drugs mezigdomide, talquetamab, and dexamethasone as treatment for any disease. The FDA has not approved mezigdomide as a treatment for any disease. The FDA has approved talquetamab for the treatment of relapsed refractory multiple myeloma in patients who have already received 4 prior lines of therapy. Dexamethasone is approved by the FDA to treat multiple diseases including multiple myeloma.

Conditions

Relapsed Refractory Multiple Myeloma (RRMM)

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort A

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.

Group Type: EXPERIMENTAL

Talquetamab

Intervention Type: 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).

Mezigdomide

Intervention Type: 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).

Dexamethasone

Intervention Type: DRUG

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

Cohort B

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.

Group Type: EXPERIMENTAL

Talquetamab

Intervention Type: 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).

Mezigdomide

Intervention Type: 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).

Dexamethasone

Intervention Type: DRUG

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

Interventions

Talquetamab

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).

Intervention Type: DRUG

Mezigdomide

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).

Intervention Type: DRUG

Dexamethasone

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

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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
• Serum bilirubin values < 1.5 x ULN. Isolated bilirubin x 1.5 x ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%. Patients with elevated bilirubin due to Gilbert's syndrome may be permitted with PI approval (e.g. total bilirubin <3 mg/dL and normal direct bilirubin); and
• Serum aspartate transaminase (ALT) and aspartate transaminase (AST) values < 2.5 × the upper limit of normal (ULN) of the institutional laboratory reference range.
• Must be able to comply with thromboembolism prophylaxis with e.g. acetylsalicylic acid (ASA), apixaban, rivaroxaban, lower molecular weight heparin, or equivalent.
• Females of childbearing potential (FCBP) must:

• Have 2 negative pregnancy tests as verified by the Investigator prior to starting study therapy. The subject must agree to ongoing pregnancy testing during the course of the study, and after end of study treatment. This applies even if the subject practices true abstinence from heterosexual contact.
• 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 two reliable forms of contraception as defined by the Pregnancy Prevention Plan.
• Male subjects must follow the mezigdomide Pregnancy Prevention Plan (see Appendix).
• Agree to follow the lifestyle considerations in Section 3.4 regarding blood donation, hospitalization and being in proximity to the hospital, and driving or operating heavy machinery.

Exclusion Criteria

• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Celgene Corporation

INDUSTRY

Sponsor Role: collaborator

Janssen Research and Development LLC

UNKNOWN

Sponsor Role: collaborator

Massachusetts General Hospital

OTHER

Sponsor Role: lead

Responsible Party

Andrew Yee, MD

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Andrew J. Yee, MD

Role: PRINCIPAL_INVESTIGATOR

Massachusetts General Hospital

Locations

Massachusetts General Hospital

Boston, Massachusetts, United States

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Countries

United States

Central Contacts

Andrew J. Yee, MD

Role: CONTACT

ayee1@mgh.harvard.edu

617-724-4000

Facility Contacts

Andrew J. Yee, MD

Role: primary

ayee1@mgh.harvard.edu

617-724-4000

Jessica Leigel, MD

Role: primary

jliegel@bidmc.harvard.edu

617-667-9920

Shonali Midha, MD

Role: primary

shonali_midha@dfci.harvard.edu

617-632-3823

Other Identifiers

25-320

Identifier Type: -

Identifier Source: org_study_id