Phase 3 Randomized Trial of Teclistamab vs. Pomalidomide, Bortezomib, Dexamethasone or Carfilzomib, Dexamethasone in Relapsed/Refractory Multiple Myeloma

The primary objective of this Phase 3 randomized study is to compare the **efficacy** of **teclistamab** monotherapy against the combination therapies of pomalidomide, bortezomib, and dexamethasone (PVd) or carfilzomib and dexamethasone (Kd) in participants with **relapsed/refractory multiple myeloma** who have received 1 to 3 prior lines of therapy, including an anti-CD38 monoclonal antibody and lenalidomide. This comparison is clinically relevant as it aims to determine the most effective treatment regimen for improving patient outcomes in this specific patient population, potentially offering a more effective therapeutic option for those with limited treatment responses.

The clinical trial involves a total of **299 participants** diagnosed with **relapsed/refractory multiple myeloma**. 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 inclusion criteria, such as having received 1 to 3 prior lines of antimyeloma therapy and demonstrating progressive disease or failure to respond to the last line of therapy. The trial includes individuals with an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 2, indicating they are fully active or capable of self-care. Participants must adhere to specified lifestyle restrictions, and female participants are required to agree not to be pregnant or breastfeeding during the study and for a specified period after the last dose of study treatment. The trial population includes vulnerable groups, ensuring a comprehensive evaluation of the treatment's efficacy across diverse demographics.

The clinical trial is designed to evaluate the efficacy of **teclistamab** monotherapy compared to a combination therapy of **pomalidomide**, **bortezomib**, and **dexamethasone** (PVd) or **carfilzomib** and **dexamethasone** (Kd) in participants with relapsed or refractory multiple myeloma. This is a Phase 3, randomized, double-blind, controlled study. The trial is expected to commence recruitment on December 19, 2022, and conclude by December 19, 2030. The primary endpoint is progression-free survival (PFS).

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as a documented diagnosis of multiple myeloma, measurable disease, and prior treatment history. The inclusion criteria require participants to have received 1 to 3 prior lines of therapy, including an anti-CD38 monoclonal antibody and lenalidomide. Participants must also have an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 2. The screening visit will assess these criteria and ensure participants are not pregnant or breastfeeding and are willing to adhere to lifestyle restrictions.

Following the screening, participants will be randomized to receive either teclistamab or the PVd/Kd regimen. The trial will include regular follow-up visits to monitor the participants' health, treatment adherence, and response to therapy. These visits will be scheduled at intervals determined by the study protocol and will include assessments such as laboratory tests, imaging, and clinical evaluations. The end-of-study visit will occur after the completion of the treatment period or upon early termination from the study.

The expected length of participant involvement in the trial is up to 1 year, with the possibility of early termination if there is evidence of disease progression, unacceptable toxicity, or withdrawal of consent. Participants will be closely monitored throughout the study to ensure safety and efficacy, with any adverse events being documented and addressed according to the study protocol.

The clinical trial involves the administration of several experimental and non-experimental treatments for participants with **relapsed or refractory multiple myeloma**. The experimental medication **teclistamab** is provided as a solution for injection, with a pharmaceutical form of solution for injection. It is administered subcutaneously, with dosing expressed in micrograms per kilogram (µg/Kg). The active substance, teclistamab, is of protein origin and is produced by Janssen-Cilag International N.V. The trial aims to compare the efficacy of teclistamab monotherapy against other treatment regimens.

**Pomalidomide** is another experimental medication used in the trial, available in hard capsule form. It is administered orally, with dosages of 1 mg, 2 mg, 3 mg, and 4 mg. The active substance, pomalidomide, is of chemical origin and is manufactured by Bristol-Myers Squibb Pharma EEIG and Janssen-Cilag International N.V. Pomalidomide is an orphan drug designated for the treatment of multiple myeloma.

The trial also includes the use of **dexamethasone**, a non-experimental treatment, available in tablet form. It is administered orally, with dosages of 2 mg, 4 mg, and 8 mg. The active substance, dexamethasone, is of chemical origin and is produced by Galenpharma GmbH, Aspen Pharma Trading Limited, and Mibe GmbH Arzneimittel. Dexamethasone is a standard-of-care therapy used in combination with other treatments.

**Bortezomib**, marketed as VELCADE, is included as a comparator treatment in the trial. It is provided as a powder for solution for injection, administered subcutaneously. The active substance, bortezomib, is of chemical origin and is manufactured by Janssen-Cilag International NV. Bortezomib is a proteasome inhibitor used in the treatment of multiple myeloma.

**Carfilzomib**, marketed as Kyprolis, is another comparator treatment used in the trial. It is available as a powder for solution for infusion, administered subcutaneously. The active substance, carfilzomib, is of chemical origin and is produced by Amgen Europe B.V. Carfilzomib is a proteasome inhibitor used in combination with dexamethasone for the treatment of multiple myeloma.

Participant compliance with the dosing schedules is monitored throughout the trial to ensure adherence to the treatment regimens. The trial is designed to evaluate the efficacy and safety of the experimental and comparator treatments in participants who have received 1 to 3 prior lines of therapy, including an anti-CD38 monoclonal antibody and lenalidomide.

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 teclistamab monotherapy against the combination therapies of pomalidomide, bortezomib, dexamethasone (PVd), or carfilzomib, dexamethasone (Kd). The assessment of PFS will be conducted according to the International Myeloma Working Group (IMWG) criteria, which provides a standardized approach to determine disease progression and response to treatment.