TRIMM-3 Study: New Combination Therapy for Multiple Myeloma

Multiple myeloma is the second most common type of blood cancer. The disease affects a specific type of white blood cell known as plasma cells. These cells are primarily found in the bone marrow. Their main function is to produce antibodies, which are essential for fighting off infections in healthy individuals.

In multiple myeloma, these cells multiply uncontrollably and produce large amounts of abnormal antibodies. This leads to a wide range of symptoms; anemia often occurs, and bones fracture due to the malignant activity of the plasma cells within the bone. Intensive treatment is therefore necessary. As is often the case with blood cancers, this treatment is divided into an initial phase to contain the disease (induction), followed by an intensive treatment phase to permanently suppress the disease (consolidation).

This is usually followed by maintenance therapy to control the disease in the long term. Effective treatment regimens are available for this purpose; however, a complete cure is rarely possible. This is also due to the fact that multiple myeloma often develops in older people, and the most intensive forms of therapy can no longer be used in these cases.

If multiple myeloma flares up again, further treatment is possible. There are a number of medications available for this. Most recently, two new antibodies, talquetamab and teclistamab, have been approved. Both represent very new mechanisms of action, as they are so-called bispecific antibodies. They “bind” to plasma cells and simultaneously activate the patient’s immune system to kill the plasma cells. Their combination with PD-1 inhibitors—which also promote the destruction of plasma cells—has not yet been approved.

The TRIMM-3 study is a Phase 1 study. The goal of the study is to test whether the combination of talquetamab with a PD-1 inhibitor or teclistamab with a PD-1 inhibitor can be administered safely and whether any adverse reactions (toxicity) occur at a borderline high dose. To this end, the first part of the study will initially identify a well-tolerated dose by administering one of the two combinations to the patient at various dosages on a biweekly schedule. In the second part of the study, the well-tolerated dose determined in this way will then be used. The study will last a maximum of 29 months (2.5 years). The study is open-label and non-randomized, meaning that both the patient and the physician know which drug combination is being administered.

Facts:

• Disease: Multiple myeloma • Cancer characteristics: Previously treated, recurrence of disease activity, no established therapy currently available • What the study investigates: New drug combination: talquetamab with a PD-1 inhibitor or teclistamab with a PD-1 inhibitor; well-tolerated dose and safety • Study objective: To assess tolerability; occurrence of side effects • Study duration: The study consists of 2 parts: determination of the well-tolerated dose; long-term administration; maximum study duration of 2.5 years. • Study characteristics: 1 study arm, open-label (assignment known)