Phase 3 Randomized Study of Alnuctamab Versus Standard Regimens in Relapsed/Refractory Multiple Myeloma: Efficacy and Safety Evaluation

The primary objective of this Phase 3, randomized, multicenter, open-label study is to evaluate the **efficacy** and **safety** of Alnuctamab compared to standard of care regimens in participants with **relapsed or refractory multiple myeloma**. The main goal is to determine if Alnuctamab can extend the duration of progression-free survival compared to standard treatments, which is clinically significant as it may offer a new therapeutic option for patients with limited treatment alternatives.

Secondary objectives include assessing overall survival, treatment efficacy, safety profile, and patient-reported outcomes regarding their experience with the treatment. These objectives are crucial for understanding the comprehensive impact of Alnuctamab on patient health and quality of life, as well as its potential role in the therapeutic landscape of multiple myeloma.

The clinical trial involves a total of **289 participants** diagnosed with **Relapsed and/or Refractory Multiple Myeloma**. The study population includes both male and female subjects, aged 18 years and older, who have received at least one but not more than three prior lines of anti-myeloma therapy. Participants must have previously been treated with lenalidomide and an anti-CD38 monoclonal antibody for at least two consecutive cycles and have achieved a minimal response or better to at least one prior anti-myeloma therapy. The trial population was selected based on these criteria, ensuring that participants have measurable disease as determined by central laboratory assessments. The study does not specify particular lifestyle considerations such as diet or physical activity. The trial includes a vulnerable population, indicating that additional ethical considerations are in place to protect these participants.

The clinical trial is designed as a **randomized**, open-label, multicenter study to evaluate the efficacy and safety of **alnuctamab** compared to standard of care regimens in participants with **relapsed or refractory multiple myeloma**. The trial aims to assess whether alnuctamab can extend progression-free survival (PFS) compared to existing treatments. The study is expected to commence recruitment on March 1, 2024, and is estimated to conclude by January 1, 2031. Participants will be involved in the study for the duration of the treatment period, which is determined by the progression of the disease or the occurrence of unacceptable toxicity.

The trial will include several study visits, beginning with a screening visit to confirm eligibility based on specific inclusion criteria, such as age and prior treatment history. Participants must have a documented diagnosis of multiple myeloma and have received at least one but not more than three prior lines of anti-myeloma therapy. The screening visit will also involve assessments to ensure measurable disease is present. Following the screening, participants will be randomized to receive either alnuctamab or a standard of care regimen. The trial will include regular follow-up visits to monitor the participants' response to treatment, assess any adverse effects, and evaluate overall survival (OS) and other secondary endpoints.

The end-of-study visit will occur after the completion of the treatment phase or upon early termination due to disease progression or adverse events. Participants may be withdrawn from the study if they experience significant side effects or if their condition worsens despite treatment. The trial will also collect data on the quality of life and any side effects experienced by participants to determine the overall safety and efficacy of alnuctamab as a treatment option for multiple myeloma.

The clinical trial involves the administration of several **experimental medications** and comparator treatments to evaluate their efficacy and safety in participants with relapsed or refractory multiple myeloma. The primary experimental medication is **Alnuctamab**, a solution for injection, administered subcutaneously. Alnuctamab, also known by its sponsor product code BMS-986349/CC-93269, is a protein-based therapeutic agent developed by Celgene Corporation. The dosing schedule and frequency of administration are determined based on the study protocol, with a maximum daily dose and total dose amount set at 9999 mg, and the treatment period is not specified beyond 9999 time units.

**Empliciti** (elotuzumab) is another experimental medication used in the trial. It is provided as a 400 mg powder for concentrate for solution for infusion, administered intravenously. Manufactured by Bristol-Myers Squibb Pharma EEIG, Empliciti is a protein-based therapeutic agent. The dosing regimen follows the study protocol, with a maximum daily and total dose amount of 9999 mg, and the treatment period is not specified beyond 9999 time units.

**DARZALEX** (daratumumab) is included as a comparator treatment. It is a solution for injection, administered intravenously, with a concentration of 1800 mg. Produced by Janssen-Cilag International NV, DARZALEX is a protein-based therapeutic agent. The dosing schedule is aligned with the study protocol, with a maximum daily and total dose amount of 9999 mg, and the treatment period is not specified beyond 9999 time units.

**Imnovid** (pomalidomide) is used as a comparator treatment in various dosages: 1 mg, 2 mg, 3 mg, and 4 mg hard capsules, administered orally. Manufactured by Bristol-Myers Squibb Pharma EEIG, Imnovid is a chemical-based therapeutic agent. The dosing regimen is determined by the study protocol, with a maximum daily and total dose amount of 9999 mg, and the treatment period is not specified beyond 9999 time units.

**Kyprolis** (carfilzomib) is another comparator treatment, provided as a 60 mg powder for solution for infusion, administered intravenously. Produced by Amgen Europe B.V., Kyprolis is a chemical-based therapeutic agent. The dosing schedule follows the study protocol, with a maximum daily and total dose amount of 9999 mg, and the treatment period is not specified beyond 9999 time units.

**Fortecortin® Inject** (dexamethasone dihydrogen phosphate disodium Ph. Eur.) is included as a comparator treatment. It is a solution for injection, administered intravenously, with a concentration of 8 mg. Manufactured by Merck Healthcare Germany GmbH, Fortecortin® Inject is a specified substance group 3 therapeutic agent. The dosing regimen is aligned with the study protocol, with a maximum daily and total dose amount of 9999 mg, and the treatment period is not specified beyond 9999 time units.

**DEXAMETHASONE** is also used as a comparator treatment, provided in tablet form for oral administration. It is a chemical-based therapeutic agent. The dosing schedule is determined by the study protocol, with a maximum daily and total dose amount of 9999 mg, and the treatment period is not specified beyond 9999 time units.

The efficacy of the clinical trial will be assessed primarily through the measurement of **progression-free survival** (PFS). This endpoint is defined as the duration from the initiation of treatment until the progression of cancer or death from any cause. Secondary endpoints include overall survival (OS), which measures the length of time participants live after starting the treatment. Additional efficacy parameters will evaluate the response of the cancer to the treatment, the duration of the response, and the time until the initiation of a new treatment regimen. The trial will also monitor any adverse effects experienced by participants and assess the impact on their quality of life. These assessments aim to determine the safety and effectiveness of alnuctamab in treating individuals with relapsed or refractory multiple myeloma.