A Phase 1b/2a, Multicenter, Open-label Study to Determine the Recommended Dose and Schedule, and Evaluate the Safety and Preliminary Efficacy of Mezigdomide in Combination with Elranatamab in Participants with Relapsed and/or Refractory Multiple Myeloma

The primary objective is to determine the safety and tolerability of mezigdomide in combination with elranatamab in participants with relapsed and/or refractory multiple myeloma (RRMM). This study aims to establish the recommended Phase 2 dose (RP2D) and optimal dosing schedule of mezigdomide when administered in combination with elranatamab in this patient population. Determining the RP2D is clinically relevant as it provides the foundation for subsequent larger clinical trials evaluating this combination therapy in RRMM.

The secondary objective is to evaluate the efficacy of mezigdomide in combination with elranatamab and to assess the presence of minimum residual disease (MRD) following study treatment among participants who achieve a complete response (CR) or better. MRD assessment provides important prognostic information regarding depth of response and potential durability of treatment outcomes in multiple myeloma.

The clinical trial enrolled a total of **38 participants** diagnosed with **relapsed or refractory multiple myeloma**. The study population included both **male** and **female** participants classified as **adults** and **elderly** individuals. Participants were selected based on specific clinical characteristics, including a documented history of relapsed or refractory multiple myeloma with prior exposure to 2 to 4 lines of **anti-myeloma therapy**. Eligible participants were required to have **measurable disease** as confirmed by local laboratory assessment and an **ECOG performance status** of 0 to 1, indicating relatively preserved functional capacity. Additional requirements included the provision of signed written informed consent, willingness to comply with hospitalization protocols, and agreement to undergo serial **bone marrow aspirations** and/or **bone marrow biopsies** during screening, throughout the study treatment period, and at the end of treatment. The trial did not involve vulnerable populations.

This clinical trial is designed as a Phase 1b/2a, multicenter, open-label study to evaluate the combination of **mezigdomide** (BMS-986348/CC-92480) and **elranatamab** (PF-06863135) in participants with **relapsed or refractory multiple myeloma** (RRMM). The study aims to determine the safety and tolerability of the combination therapy and to establish the **recommended Phase 2 dose** (RP2D) and dosing schedule of mezigdomide when administered with elranatamab. The trial is non-randomized and does not employ blinding procedures, allowing all participants to receive the investigational treatment combination. The overall trial duration is estimated to extend from September 2025 to March 2032, with recruitment expected to commence in September 2025.

The primary objectives of this study include assessment of the type, frequency, seriousness, and severity of all **adverse events** (aAEs) and determination of the RP2D and optimal dosing schedule for the combination regimen. Secondary objectives focus on evaluating treatment efficacy through multiple parameters, including **overall response rate** (ORR), **very good partial response rate** (VGPRR), **complete response rate** (CRR), **time to response** (TTR), **duration of response** (DOR), **progression-free survival** (PFS), and **overall survival** (OS). Additionally, the study will assess the **minimum residual disease negativity rate** to determine the proportion of participants achieving undetectable disease using sensitive laboratory testing methods.

Eligible participants must have a confirmed diagnosis of RRMM with a history of 2 to 4 prior lines of anti-myeloma therapy. Participants are required to have measurable disease as determined by local laboratory assessment and must demonstrate an **Eastern Cooperative Oncology Group Performance Status** (ECOG PS) of 0 to 1. Additional inclusion criteria include provision of signed written informed consent, agreement to comply with hospitalization requirements, and consent to undergo serial **bone marrow aspirations** (BMAs) and/or **bone marrow biopsies** (BMBs) during screening, study treatment, and at end of treatment (EOT).

The investigational medicinal products include mezigdomide administered as an **oral capsule** in various formulations, elranatamab administered as a **solution for injection** via **intravenous infusion**, and **dexamethasone** administered as an oral tablet. Mezigdomide contains the active substance mezigdomide of chemical origin, elranatamab contains the active substance elranatamab of biological/biotechnological origin (protein), and dexamethasone contains the active substance dexamethasone of chemical origin. All products are manufactured by Celgene Corporation except elranatamab, which is manufactured by Pfizer Inc.

Participant involvement in the study will vary depending on individual response to treatment and tolerance of the investigational regimen. The study protocol includes a screening visit for eligibility assessment, regular follow-up visits during the treatment period for safety monitoring and efficacy evaluation, and an end-of-study visit. During the treatment phase, participants will undergo scheduled assessments including physical examinations, laboratory tests, bone marrow evaluations, and adverse event monitoring. Conditions that may lead to early termination from the study include unacceptable toxicity, disease progression, participant withdrawal of consent, investigator decision based on safety concerns, or other protocol-specified criteria. The study design allows for ongoing assessment of both safety and preliminary efficacy throughout the treatment period to inform dose optimization and future clinical development of this combination therapy for relapsed or refractory multiple myeloma.

The experimental medication mezigdomide (also designated as CC-92480 or BMS-986348/CC-92480) is administered as a capsule formulation via the oral route. Mezigdomide is a chemical substance manufactured by Celgene Corporation and serves as the active substance in multiple capsule strengths utilized in this clinical trial. The investigational medicinal product is supplied in various dosage forms to allow for dose escalation and optimization during the study phases.

Elranatamab (sponsor product code PF-06863135) is administered as a solution for injection via intravenous infusion. This experimental medication is of biological/biotechnological origin, specifically classified as a protein therapeutic, and is manufactured by Pfizer Inc. Elranatamab represents a biologic agent that is combined with mezigdomide in the treatment regimen for participants with relapsed and/or refractory multiple myeloma.

Dexamethasone is utilized in this clinical trial as a non-experimental treatment component. This medication is administered as a tablet via the oral route. Dexamethasone is a chemical substance that serves as a standard-of-care therapy component in the management of multiple myeloma and is used in combination with the experimental agents in this study protocol.

Efficacy will be assessed through multiple parameters in this clinical trial. The primary efficacy endpoints include the overall response rate (ORR), defined as the percentage of participants who respond to treatment. Additional response metrics comprise the very good partial response rate or better (VGPRR) and the complete response rate or better (CRR). Time to response (TTR) will be evaluated to determine the duration required for the treatment to demonstrate initial efficacy. Duration of response (DOR) will measure the length of time the therapeutic effect is maintained. Progression-free survival (PFS) will assess the time interval until disease progression occurs. Overall survival (OS) will be monitored to evaluate participant survival following treatment initiation. The minimum residual disease negativity rate will be determined to identify participants without detectable disease using sensitive laboratory testing. Measurable disease will be determined by local laboratory assessments. Serial bone marrow aspirations and bone marrow biopsies will be performed during screening, study treatment, and at end of treatment to support efficacy evaluations.