A Phase 3, Two-stage, Randomized, Multicenter, Open-label Study Comparing Mezigdomide (CC-92480/BMS-986348), Carfilzomib, and Dexamethasone (MeziKd) Versus Carfilzomib and Dexamethasone (Kd) in Participants with Relapsed or Refractory Multiple Myeloma (RRMM): SUCCESSOR-2

The primary objective of this Phase 3, two-stage, randomized, multicenter, open-label study is to compare the **progression-free survival (PFS)** of a combination therapy consisting of Mezigdomide (CC-92480/BMS-986348), Carfilzomib, and Dexamethasone (MeziKd) against the standard regimen of Carfilzomib and Dexamethasone (Kd) in participants with **relapsed or refractory multiple myeloma (RRMM)**. This objective is clinically relevant as it aims to determine whether the addition of Mezigdomide to the existing treatment regimen can extend the duration during which the disease does not worsen, thereby potentially improving patient outcomes in this challenging condition.

The clinical trial involves a total of **268 participants** diagnosed with **Relapsed or Refractory Multiple Myeloma (RRMM)**. The study population includes both male and female subjects, with an age range corresponding to categories 3 and 4, which typically represent adults and older adults. Participants were selected based on specific criteria, including a documented diagnosis of multiple myeloma with measurable disease and having received at least one prior line of anti-myeloma therapy. The trial includes individuals who have previously been treated with lenalidomide and an anti-CD38 monoclonal antibody and have shown minimal response or better to at least one prior therapy. Participants must have experienced disease progression during or after their last treatment regimen and have an Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2. The trial population is inclusive of vulnerable groups, and lifestyle factors such as diet and physical activity are not specified in the available data.

The clinical trial is designed as a **randomized**, open-label, multicenter study to evaluate the efficacy of **mezigdomide** (CC-92480) in combination with **carfilzomib** and **dexamethasone** compared to carfilzomib and dexamethasone alone in participants with **relapsed or refractory multiple myeloma** (RRMM). The primary objective is to assess progression-free survival (PFS) between the two treatment arms. The trial is expected to run from September 2022 to July 2029, with a maximum treatment period of 82 weeks for each participant.

Participants will undergo a series of study visits, beginning with a screening visit to confirm eligibility based on criteria such as documented diagnosis of multiple myeloma, measurable disease, and prior treatment history. Following randomization, participants will attend regular follow-up visits to monitor treatment response and safety. These visits will include assessments such as laboratory tests, imaging studies, and clinical evaluations. The end-of-study visit will occur after the completion of the treatment period or upon early termination.

The expected length of participant involvement is up to 82 weeks, contingent upon individual response and tolerability. Conditions that may lead to early termination from the study include disease progression, unacceptable toxicity, or withdrawal of consent. The trial will adhere to rigorous scientific and ethical standards to ensure the validity and reliability of the results.

The clinical trial involves the administration of several treatments, including the experimental medication **CC-92480**. This compound, also known as **mezigdomide**, is provided in a **capsule** form for **oral** administration. The dosage varies, with a maximum daily dose ranging from 0.2 mg to 1 mg, depending on the specific formulation used. The total maximum dose over the treatment period of 82 days ranges from 373.8 mg to 1869 mg. The active substance is of chemical origin, and the product is developed by Celgene Corporation. Participant compliance with the dosing schedule is monitored throughout the trial.

Another key component of the trial is **Kyprolis**, which contains the active substance **carfilzomib**. This medication is supplied as a **powder for solution for infusion** and is administered via **intravenous infusion**. The maximum daily dose is 56 mg/m², with a total maximum dose of 29832 mg/m² over the 82-day treatment period. Kyprolis is manufactured by Amgen Europe B.V. and is classified as an orphan drug, indicating its use in treating rare conditions.

In addition to the experimental treatments, the trial includes the administration of **dexamethasone** as a standard-of-care therapy. Dexamethasone is available in both **tablet** and **solution for injection** forms, allowing for **oral** or **intravenous** administration. The maximum daily dose is 40 mg, with a total maximum dose of 14240 mg over the course of the trial. This medication is of chemical origin and is utilized to manage symptoms and enhance the efficacy of the primary treatments.

The efficacy of the clinical trial will be assessed by evaluating the **progression-free survival (PFS)** of participants. PFS is defined as the time from randomization to the first documentation of progressive disease (PD) according to the International Myeloma Working Group (IMWG) Uniform Response Criteria for Multiple Myeloma or death due to any cause, whichever occurs first. This primary endpoint will be used to compare the efficacy of the combination of **mezigdomide** (CC-92480), **carfilzomib**, and **dexamethasone** (480Kd) against the combination of carfilzomib and dexamethasone (Kd) in participants with relapsed or refractory multiple myeloma (RRMM).