A Phase 3 Randomized Study Comparing Talquetamab in Combination with Pomalidomide (Tal-P), Talquetamab in Combination with Teclistamab (Tal-Tec), and Investigator’s Choice of Either Elotuzumab, Pomalidomide, and Dexamethasone (EPd) or Pomalidomide, Bortezomib, and Dexamethasone (PVd) in Participants with Relapsed or Refractory Myeloma who Have Received 1 to 4 Prior Lines of Therapy Including an Anti-CD38 Antibody and Lenalidomide

The primary objective of this Phase 3 randomized study is to compare the **efficacy** of two treatment combinations involving **talquetamab**: Talquetamab in combination with Pomalidomide (Tal-P) and Talquetamab in combination with Teclistamab (Tal-Tec), against the investigator's choice of either Elotuzumab, Pomalidomide, and Dexamethasone (EPd) or Pomalidomide, Bortezomib, and Dexamethasone (PVd) in participants with **relapsed or refractory myeloma** who have received 1 to 4 prior lines of therapy, including an anti-CD38 antibody and lenalidomide. This comparison is clinically relevant as it aims to identify more effective treatment regimens for patients with limited therapeutic options, potentially improving outcomes in this challenging patient population.

The clinical trial involves a total of **462 participants** diagnosed with **relapsed or refractory myeloma**. The study population includes both male and female subjects, aged 18 years and older, encompassing adults and older adults. Participants were selected based on specific inclusion criteria, including a documented diagnosis of multiple myeloma according to the International Myeloma Working Group (IMWG) diagnostic criteria, and evidence of measurable disease at screening. The trial also considers individuals with relapsed or refractory disease, as defined by the IMWG criteria, and those with an Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2. The trial population includes a vulnerable population, indicating that additional ethical considerations are in place. Lifestyle factors such as diet, physical activity, or habits are not specified in the available data.

The clinical trial is designed to evaluate the efficacy of **talquetamab** in combination with other therapeutic agents in participants with **relapsed or refractory myeloma**. This is a Phase 3, randomized, double-blind, controlled study. Participants will be randomly assigned to receive either talquetamab in combination with **pomalidomide** (Tal-P), talquetamab in combination with **teclistamab** (Tal-Tec), or the investigator's choice of either **elotuzumab**, pomalidomide, and **dexamethasone** (EPd) or pomalidomide, **bortezomib**, and dexamethasone (PVd). The primary endpoint of the study is progression-free survival.

The trial is expected to commence recruitment on February 22, 2024, and is estimated to conclude by June 14, 2027. The total duration of the trial for each participant is anticipated to be up to 24 months, depending on individual response and progression. Participants will undergo a series of study visits, beginning with a screening visit to confirm eligibility based on inclusion criteria such as age, documented multiple myeloma, and relapsed or refractory disease status. Follow-up visits will be scheduled regularly to monitor treatment response, safety, and any adverse events. The end-of-study visit will occur after the completion of the treatment period or upon early termination.

Participants may be withdrawn from the study early if they experience unacceptable toxicity, disease progression, or if they withdraw consent. The study will adhere to rigorous ethical standards and regulatory requirements to ensure participant safety and data integrity. The trial aims to provide valuable insights into the comparative efficacy of these treatment regimens in managing relapsed or refractory myeloma.

The clinical trial involves the administration of several experimental and non-experimental treatments to participants with **relapsed or refractory myeloma**. The experimental medication **talquetamab** is provided as a solution for injection, with a maximum daily dose of 800 µg/kg and a total dose limit of 25,600 µg/kg over a 24-week period. It is administered subcutaneously. **Teclistamab**, another experimental treatment, is also a solution for injection, administered subcutaneously at a maximum daily dose of 3 mg/kg, with a total dose limit of 96 mg/kg over the same period.

**Pomalidomide** is used in various formulations, including 1 mg, 2 mg, 3 mg, and 4 mg hard capsules. It is administered orally with a maximum daily dose of 4 mg and a total dose limit of 2,184 mg over 24 weeks. **Bortezomib**, marketed as Velcade, is provided as a powder for solution for injection, administered subcutaneously with a maximum daily dose of 20 mg and a total dose limit of 760 mg over the treatment period.

**Elotuzumab** is available in two formulations: 300 mg and 400 mg powders for concentrate for solution for infusion. It is administered intravenously with a maximum daily dose of 20 mg and a total dose limit of 640 mg over 24 weeks. **Dexamethasone** is provided in tablet form, with available dosages of 2 mg, 4 mg, and 8 mg. It is administered orally with a maximum daily dose of 40 mg and a total dose limit of 4,160 mg over the treatment period.

Participant compliance is monitored through regular assessments and adherence checks to ensure the correct administration of the medications as per the dosing schedules. The trial includes both experimental treatments and standard-of-care therapies, allowing for a comprehensive evaluation of the efficacy of the experimental combinations compared to established treatment regimens.

The efficacy of the clinical trial will be assessed primarily through the endpoint of **Progression-Free Survival** (PFS). This endpoint is a critical measure in evaluating the effectiveness of the treatment regimens being tested, which include Talquetamab in combination with Pomalidomide (Tal-P), Talquetamab in combination with Teclistamab (Tal-Tec), and the investigator’s choice of either Elotuzumab, Pomalidomide, and Dexamethasone (EPd) or Pomalidomide, Bortezomib, and Dexamethasone (PVd). The trial is designed for participants with relapsed or refractory multiple myeloma who have received 1 to 4 prior lines of therapy, including an anti-CD38 antibody and Lenalidomide.

The assessment of PFS will involve regular monitoring of participants to determine the time from randomization until disease progression or death from any cause. The trial will utilize central laboratory assessments to confirm measurable disease at screening, defined by specific criteria such as serum M-protein levels, urine M-protein levels, or serum immunoglobulin free light chain levels. The trial will follow the International Myeloma Working Group (IMWG) criteria for defining disease progression and response to treatment. The schedule for measuring and collecting data on PFS will be aligned with the trial's protocol, ensuring consistent and accurate data collection throughout the study duration.