Talquetamab in Combination With Iberdomide and Dexamethasone for Relapsed or Refractory Multiple Myeloma

Multiple Myeloma Clinical Trial

Official title: A Phase Ib, Multi-center, Study of Talquetamab in Combination With Iberdomide and Dexamethasone for the Treatment of Relapsed or Refractory Multiple Myeloma

Status Not yet recruiting

Clinical Trial Summary

This phase I trial tests the safety, side effects, and best dose of talquetamab in combination with iberdomide and dexamethasone in treating patients with multiple myeloma that has come back after a period of improvement (relapsed) or has not responded to previous treatment (refractory). There is currently a significant unmet need for patients with relapsed or refractory multiple myeloma (RRMM) who are triple class refractory and have been exposed to B-cell maturation antibody (BCMA) targeted therapy. These patients currently have limited treatment options and poor survival. Talquetamab is approved for use by the Food and Drug Administration (FDA) to treat RRMM when given alone. Talquetamab can bring T-cells to the myeloma cell, resulting in myeloma cell death. Iberdomide is an investigational drug. Iberdomide works by targeting and destroying proteins that help myeloma cancer cells to survive. Dexamethasone is a corticosteroid, is similar to a natural hormone produced by the adrenal glands. It relieves inflammation (swelling, heat, redness, and pain) and is used to treat certain types of cancer including myeloma. Giving talquetamab in combination with iberdomide and dexamethasone may be safe, tolerable and effective in treating patients with RRMM

Clinical Trial Description

PRIMARY OBJECTIVES:

I. To assess safety of the combination of talquetamab (Tal), iberdomide (Iber) and dexamethasone (Dex) in patients with triple class exposed (TCE) RRMM. (Phase 1b-dose escalation (DE)).

II. To assess dose limiting toxicity (DLT) and determine the recommended phase 2 dose (RP2D) of the combination of Tal, Iber and Dex administered in 28-day cycles in patients with TCE RRMM. (Phase 1b-DE) III. To further assess safety of RP2D of the combination of Tal, Iber and Dex administered in 28-day cycles in patients with TCE RRMM Len-refractory, and having received >= 2 prior lines of therapy. (Phase 1b-expansion (Exp)) IV. To assess overall response rate (ORR) in patients with TCE RRMM, Len-refractory, and having received ≥ 2 prior lines of therapy. (Phase 1b-Exp).

SECONDARY OBJECTIVES:

I. To assess ORR, and to determine minimal residual disease (MRD) negative (-) rates in patients achieving ≥ very good partial remission (VGPR).

II. To assess toxicity (incidence of adverse events (AEs), serious AEs (SAEs), and treatment discontinuation due to toxicity) and safety (physical examination findings, vital signs, and clinical laboratory evaluations) in patients with RRMM.

III. Describe changes in health-related quality of life (HRQoL) using the European Organization for Research and Treatment of Cancer (C30) -Quality of Life questionnaire (QLQ) (EORTC-QLQ-C30) and EORTC QLQ-Multiple Myeloma Questionnaire (MY20)).

EXPLORATORY OBJECTIVES:

I. To assess serial cytokines levels with treatment of the combination of Tal, Iber and Dex and predictive values of response, cytokine release syndrome (CRS) and other adverse events.

II. To assess changes in immune cells in blood and bone marrow with treatment of the combination of Tal, Iber and Dex.

III. To determine the efficacy of combination of Tal, Iber and Dex defined as achieving complete response (CR) and MRD (-) status and correlation between mass spectroscopy and bone marrow (BM) MRD assessments.

OUTLINE: This is a dose-escalation study of Iber followed by a dose-expansion study.

Patients receive Tal subcutaneous (SQ) over 1-3 minutes on days 1, 4, 8, and 15 of cycle 1, days 1 and 15 of cycles 2-6, and day 1 of cycle 7 and subsequent cycles, Iber orally (PO) once daily (QD) on days -7 thru day 14 of cycle 1 and days 1-21 of cycle 2 and subsequent cycles, and Dex PO on days 1, 4, 8, 15, and 22 of cycle 1 and on days 1, 8, 15, and 22 of cycles 2-4, but may be continued at the discretion of the investigator. Treatment repeats every 35 days for cycle 1 and then every 28 days for subsequent cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo bone marrow biopsy, skeletal x-ray, computed tomography (CT), positron emission tomography (PET)/CT, or magnetic resonance imaging (MRI), tissue and blood sample collection throughout the study.

After completion of study treatment, patients are followed up at 30 days every 8 weeks for up to 2 years or until progression or initiation of subsequent therapy. ;

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell
• Refractory Multiple Myeloma
• Relapsed Multiple Myeloma

• NCT number: NCT06348108
• Study type: Interventional
• Source: University of California, San Francisco
• Contact: Kenya Gomez
• Phone: 877-827-3222
• Email: Kenya.Gomez@ucsf.edu
• Status: Not yet recruiting
• Phase: Phase 1
• Start date: July 1, 2024
• Completion date: June 30, 2028