Phase 3 Randomized Trial of Teclistamab Plus Daratumumab SC vs. Daratumumab SC with Pomalidomide and Dexamethasone or Bortezomib and Dexamethasone in Relapsed/Refractory Multiple Myeloma

The primary objective of this Phase 3 randomized study is to compare the **efficacy** of Teclistamab in combination with Daratumumab SC (Tec-Dara) against two other treatment regimens: Daratumumab SC, Pomalidomide, and Dexamethasone (DPd) or Daratumumab SC, Bortezomib, and Dexamethasone (DVd) in participants with **relapsed or refractory multiple myeloma**. This comparison is clinically relevant as it aims to determine the most effective treatment combination for improving patient outcomes in this challenging condition, which is characterized by the recurrence or resistance to standard therapies.

The clinical trial involves a total of **219 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 documented multiple myeloma according to the International Myeloma Working Group diagnostic criteria, measurable disease at screening, and having received 1 to 3 prior lines of antimyeloma therapy. The trial also considers individuals with an Eastern Cooperative Oncology Group performance status score of 0, 1, or 2, indicating they are ambulatory and capable of self-care. The trial population includes a vulnerable population, and participants are required to have clinical laboratory values within a specified range. 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 a combination therapy involving **teclistamab** and **daratumumab** in comparison to other treatment regimens in participants with **relapsed or refractory multiple myeloma**. This is a Phase 3, randomized, double-blind, controlled study. The trial is expected to span approximately five years, with an estimated recruitment start date of October 25, 2021, and an estimated end date of October 25, 2026.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on specific criteria, such as documented multiple myeloma and previous treatment history. The trial will include regular follow-up visits to monitor the participants' response to the treatment and any adverse effects. The end-of-study visit will conclude the participant's involvement, during which final assessments will be conducted to evaluate the primary endpoint of progression-free survival (PFS).

The expected length of participant involvement in the trial is contingent upon the individual's response to the treatment and the overall progression of the disease. Participants may be subject to early termination from the study if they experience unacceptable toxicity, withdraw consent, or if the investigator determines it is in the participant's best interest to discontinue. The trial will adhere to rigorous scientific and ethical standards to ensure the safety and well-being of all participants throughout the study duration.

The clinical trial involves several experimental medications, each with specific pharmaceutical forms, dosages, and administration routes. **Dexamethason 8 mg GALEN® Tabletten** is administered orally in tablet form. The active substance is **dexamethasone**, a chemical compound, and the product is repackaged and relabeled for the trial. The maximum treatment period is one day, with no specified maximum daily or total dose.

**Dexamethasone Tablets BP 2.0mg** are also administered orally in tablet form. The active substance is **dexamethasone Ph. Eur.**, categorized under Specified Substance Group 3. This product is similarly repackaged and relabeled, with a maximum treatment period of one day.

**VELCADE 3.5 mg powder for solution for injection** is administered subcutaneously. The active substance is **bortezomib**, a chemical compound. The product is repackaged and relabeled, with a maximum treatment period of one day.

**Imnovid 3 mg hard capsules** are administered orally. The active substance is **pomalidomide**, a chemical compound. This product is designated as an orphan drug and is repackaged and relabeled, with a maximum treatment period of one day.

**Pomalidomide** is administered orally in hard capsule form. The active substance is **pomalidomide**, a chemical compound. The product is not repackaged or relabeled, with a maximum treatment period of one day.

**DARZALEX 1800 mg solution for injection** is administered subcutaneously. The active substance is **daratumumab**, a protein of other origin. This product is designated as an orphan drug and is repackaged and relabeled, with a maximum treatment period of one day.

**Teclistamab** is administered subcutaneously in solution for injection form. The active substance is **teclistamab**, a protein of other origin. The product is not repackaged or relabeled, with a maximum treatment period of one day.

**Privigen 100 mg/ml solution for infusion** is administered intravenously. The active substance is **human normal immunoglobulin**, a structurally diverse substance derived from blood. The product is repackaged and relabeled, with a maximum treatment period of one day.

Non-experimental treatments in the study include standard-of-care therapies such as **dexamethasone** in various formulations, **bortezomib**, and **pomalidomide**. These treatments are administered according to standard clinical practice, with compliance monitored through regular assessments and documentation. The trial aims to compare the efficacy of the combination of **teclistamab** and **daratumumab** with other treatment regimens in participants with relapsed or refractory multiple myeloma.

The efficacy of the clinical trial will be assessed by comparing the treatment regimens in participants with relapsed or refractory **Multiple Myeloma**. The primary endpoint for evaluating efficacy is Progression-Free Survival (PFS). This endpoint will be measured to determine the length of time during and after the treatment that a participant lives with the disease without it getting worse. The trial involves a Phase 3 randomized study comparing Teclistamab in combination with Daratumumab SC (Tec-Dara) versus Daratumumab SC, Pomalidomide, and Dexamethasone (DPd) or Daratumumab SC, Bortezomib, and Dexamethasone (DVd).