A Phase 3b, Multicenter, Open-label, Daratumumab Long-term Extension Study

The primary objective of this Phase 3b, multicenter, open-label study is to provide ongoing access to study treatments for participants with **multiple myeloma** or smoldering multiple myeloma who are benefiting from treatment in certain Janssen R&D studies that incorporate **daratumumab** as part of the regimen. This includes access for all participants regardless of treatment group in daratumumab studies and access to participants in daratumumab-containing arms in non-daratumumab studies, from studies that have reached clinical cutoff for final analysis. The clinical relevance of this objective lies in ensuring continued therapeutic benefit and monitoring long-term safety for patients who have shown positive responses to daratumumab, a monoclonal antibody used in the treatment of multiple myeloma. Certain long-term safety data will continue to be collected from study participants.

The clinical trial involves a total of **103 participants** diagnosed with **Multiple Myeloma** or smoldering multiple myeloma. The study population includes both male and female subjects, with an age range that corresponds to categories 3 and 4, indicating adult and elderly participants. The trial population was selected based on their active participation in certain Janssen R&D studies involving daratumumab, where they continue to benefit from the treatment without experiencing disease progression or unmanageable toxicity. Participants are required to adhere to specific lifestyle restrictions as outlined in the study protocol. The trial includes a vulnerable population, and both genders are represented. Key inclusion criteria necessitate that participants must be actively receiving daratumumab or other study treatments and have not met withdrawal criteria from the parent study. The study ensures ongoing access to treatment for those benefiting from it, while also collecting long-term safety data.

The clinical trial is designed as a **Phase 3b**, multicenter, open-label study to evaluate the long-term safety of **daratumumab** in combination with standard treatment regimens for **multiple myeloma**. The trial aims to provide ongoing access to study treatments for participants who are benefiting from treatment in certain Janssen R&D studies that include daratumumab. The study will continue until no more patients require access to daratumumab through this trial, with an estimated end date of January 31, 2029.

Participants will be enrolled if they are actively receiving daratumumab, either as monotherapy or in combination with other treatments, and continue to benefit from the study treatment without experiencing disease progression or unmanageable toxicity. The trial will include a series of study visits, beginning with a screening visit to confirm eligibility based on the inclusion criteria. Follow-up visits will be conducted to monitor the safety and efficacy of the treatment, and to collect long-term safety data. The end-of-study visit will occur when the participant discontinues the study treatment or gains alternative access to daratumumab.

The expected length of participant involvement is contingent upon the continued benefit from the study treatment, with a maximum treatment period of 28 days per cycle. Conditions that may lead to early termination from the study include disease progression, unmanageable toxicity, or meeting withdrawal criteria set forth in the parent study. Participants must adhere to specific lifestyle restrictions and contraceptive measures as outlined in the protocol. The study is not categorized as low intervention, and it is conducted under strict adherence to ethical guidelines and regulatory requirements.

The clinical trial involves the administration of several experimental and non-experimental treatments for participants with **multiple myeloma** or smoldering multiple myeloma. The primary experimental medication is **DARATUMUMAB**, a biological and human monoclonal antibody, provided as a 20 mg/mL concentrate for solution for infusion. It is administered intravenously with a maximum daily dose of 16 mg/kg over a treatment period of 28 days. Additionally, DARATUMUMAB is available as an 1800 mg solution for injection, also administered intravenously, with the same dosing schedule.

**DEXAMETHASONE SODIUM PHOSPHATE** is used as an auxiliary treatment in the form of a solution for infusion. The maximum daily dose is 40 mg, administered via infusion over a 28-day period. Another form of dexamethasone, provided as a tablet, is also included in the study with the same dosage and treatment duration, administered orally.

**POMALIDOMIDE** is administered as a 4 mg hard capsule, taken orally. The maximum daily dose is 4 mg, with a treatment period of 28 days. This medication is classified as an orphan drug, indicating its use for rare conditions.

**LENALIDOMIDE** is provided in capsule form, with a maximum daily dose of 25 mg, administered orally over a 28-day period. This chemical compound is used as an auxiliary treatment in the study.

**CARFILZOMIB** is administered as a 60 mg powder for solution for infusion, with a maximum daily dose of 70 mg/m². It is given intravenously over a 28-day treatment period and is also classified as an orphan drug.

All treatments are monitored for participant compliance, and the study aims to provide ongoing access to these medications for participants benefiting from the treatment. The trial collects long-term safety data to ensure the efficacy and safety of the treatments provided.

Efficacy in this clinical trial will be assessed primarily by determining when no more patients require continued access to **Daratumumab** via the study. This endpoint is reached when participants have either discontinued study treatment or have alternative access to **Daratumumab**. The trial is designed to provide ongoing access to study treatments for participants with multiple myeloma or smoldering multiple myeloma who are benefiting from treatment in certain Janssen R&D studies that include **Daratumumab** as part of the regimen. The study will continue to collect long-term safety data from participants. The trial is a Phase 3b, multicenter, open-label, long-term extension study, with an estimated end date of January 31, 2029. The trial began recruitment on March 1, 2023. Participants must be actively receiving **Daratumumab** or other study treatments in a Janssen R&D **Daratumumab** study and continue to benefit from the treatment without experiencing disease progression or unmanageable toxicity. The trial will ensure that participants have not met withdrawal criteria from the parent study and have received the last dose of study treatment within the previous three months.