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

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), EORTC QLQ Oral Health 15 (OH-15) and EORTC QLQ-Multiple Myeloma Questionnaire (MY20)). EXPLORATORY OBJECTIVES: I. To assess serum cytokines levels with treatment of the combination of Tal, Iber and Dex and the 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 Objective Response Rate (ORR) and 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. Participants receive Tal in cycle 1 then all 3 drugs will be given in combination in cycle 2 but may be continued at the discretion of the investigator. Cycles repeat every 28 days for as long as there is clinical benefit as determined by the Investigator. Study treatment will be discontinued if there is unacceptable toxicity, disease progression, withdrawal of consent by the participant, noncompliance with study requirements, intercurrent illness, or closure of the study by the Sponsor. After completion of study treatment, patients are followed up at 30 days every 8 weeks for up to 3 years or until progression or initiation of subsequent therapy.