Phase 3 Randomized Trial of Talquetamab, Daratumumab, and Pomalidomide Combinations in Relapsed/Refractory Multiple Myeloma Post-One Therapy Line

The primary objective of this Phase 3 randomized study is to compare the **efficacy** of two treatment combinations involving Talquetamab and Daratumumab, specifically Talquetamab SC in combination with Daratumumab SC and Pomalidomide (Tal-DP) and Talquetamab SC in combination with Daratumumab SC (Tal-D), against the established regimen of Daratumumab SC, Pomalidomide, and Dexamethasone (DPd) in participants with **relapsed or refractory multiple myeloma** who have received at least one prior line of therapy. This comparison is clinically relevant as it aims to determine the most effective treatment strategy for improving patient outcomes in this challenging condition.

The clinical trial involves a total of **504 participants** diagnosed with **Relapsed or Refractory Multiple Myeloma**. The study population includes both male and female subjects, with an age range that encompasses adults and older adults. Participants were selected based on specific inclusion criteria, such as having a documented diagnosis of multiple myeloma according to the International Myeloma Working Group (IMWG) diagnostic criteria, and having measurable disease at screening. The trial also considers individuals with relapsed or refractory disease, as defined by IMWG criteria, and those who have received at least one prior line of antimyeloma therapy, including a proteasome inhibitor and lenalidomide. Participants must have an Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2. The trial population includes a vulnerable population, indicating that special considerations are in place to ensure their safety and well-being throughout the study. Lifestyle factors such as diet and physical activity are not specified in the available data.

The clinical trial is designed to evaluate the efficacy of **talquetamab** in combination with **daratumumab** and **pomalidomide** compared to a regimen of **daratumumab**, **pomalidomide**, and **dexamethasone** in participants with relapsed or refractory multiple myeloma. This is a Phase 3, randomized, double-blind, controlled study. The trial is expected to last until May 28, 2029, with recruitment having commenced on October 13, 2022. Participants will be randomly assigned to one of the treatment arms, ensuring a balanced distribution of baseline characteristics.

The study involves several key visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as documented multiple myeloma, relapsed or refractory disease status, and prior treatment history. Participants must have received at least one prior line of antimyeloma therapy, including a proteasome inhibitor and lenalidomide. The screening visit will also assess the Eastern Cooperative Oncology Group (ECOG) performance status. Following randomization, participants will attend regular follow-up visits to monitor treatment response, adverse events, and overall health status. The primary endpoint of the study is progression-free survival, with secondary endpoints to be determined. The end-of-study visit will conclude the participant's involvement, assessing final outcomes and any long-term effects of the treatment.

Participant involvement is expected to last up to 172 weeks, corresponding to the maximum treatment period. Conditions that may lead to early termination from the study include significant adverse events, withdrawal of consent, or investigator decision based on the participant's best interest. The trial is conducted under strict adherence to ethical guidelines and regulatory requirements, ensuring the safety and well-being of all participants throughout the study duration.

The clinical trial involves the administration of several experimental and non-experimental treatments to participants with **relapsed or refractory multiple myeloma**. The experimental medication **Pomalidomide** is provided in the form of hard capsules, with a maximum daily dose of 4 mg and a total dose of 3612 mg over a treatment period of 172 days. The route of administration is oral, and the medication is manufactured by Janssen-Cilag International N.V. and Bristol-Myers Squibb Pharma EEIG. Compliance with the dosing schedule is monitored throughout the trial.

Another experimental treatment, **DARZALEX 1800 mg solution for injection**, contains the active substance **Daratumumab**. This medication is administered subcutaneously with a maximum daily dose of 1800 mg and a total dose of 95400 mg over the same treatment period. The product is re-labeled and re-packaged for the clinical trial and is provided by Janssen-Cilag International NV.

**Talquetamab**, under the product name JNJ-64407564, is also used in the trial. It is a solution for injection administered subcutaneously, with a maximum daily dose of 800 µg/kg and a total dose of 68470 µg/kg over 172 days. This biological product is provided by Janssen-Cilag International N.V. and is designated as an orphan drug.

The trial also includes the use of **Dexamethasone** in tablet form, with a maximum daily dose of 40 mg and a total dose of 6880 mg over the treatment period. The tablets are provided by Aspen Pharma Trading Limited, Merck Healthcare Germany GmbH, and MIBE GmbH Arzneimittel. The administration route is oral, and the tablets are re-labeled and re-packaged for the trial.

Participant compliance with the dosing schedules is closely monitored to ensure adherence to the treatment protocols. The trial aims to compare the efficacy of the combination therapies involving these medications in participants who have received at least one prior line of therapy.

The efficacy of the clinical trial will be assessed by evaluating the primary endpoint of **Progression-Free Survival** (PFS) in participants with relapsed or refractory multiple myeloma. This endpoint will measure the length of time during and after the treatment that a participant lives with the disease without it getting worse. The trial aims to compare the efficacy of Talquetamab in combination with Daratumumab and Pomalidomide (Tal-DP) or Talquetamab in combination with Daratumumab (Tal-D) versus Daratumumab, Pomalidomide, and Dexamethasone (DPd).