EAA242 - Phase Ib/II Fixed Duration Study of Teclistamab/Pomalidomide (TP) versus Carfilzomib/Pomalidomide/Dexamethasone (KPd) in Early Relapse of Multiple Myeloma

The standard initial therapy for patients with newly diagnosed multiple myeloma typically includes a three-step approach. First, patients receive three or four different drugs in combination (targeted therapies, immunotherapies, and steroids). If they are healthy enough, they might also have a stem cell transplant afterward. Then, they take lower doses of medicines for 2-3 years or longer to help control the cancer and stay in remission. This treatment approach has significantly extended overall survival for many patients, with about 62% living at least 5 years after diagnosis.

However, multiple myeloma is usually not curable. Many patients will see the cancer come back at some point. Some may even experience a return of cancer during or shortly after frontline treatment, known as an early relapse. This is typically due to aggressive disease or the presence of genetic mutations in tumors that put these patients at higher risk. There is no established standard-of-care regimen for patients with an early relapse.  Researchers are still studying the best treatment approach.

The EAA242 trial was designed with this in mind. It aims to identify a new treatment option for patients with multiple myeloma who have already been treated with one line of lenalidomide-based therapy, and targeted immunotherapy, specifically, an anti-CD38 monoclonal antibody (daratumumab or isatuximab). The study is evaluating teclistamab, which directs T-cells to attack myeloma cells, in combination with pomalidomide, a drug that helps stimulate the body’s immune system to fight myeloma. 

Combination therapy with teclistamab and pomalidomide (TP) is already being given to patients with relapsed or refractory multiple myeloma. The study team hypothesizes that introducing this type of immune‑based treatment earlier in the disease course will lead to better results in the early relapse setting. To assess this idea, they are comparing TP with the commonly used regimen of carfilzomib, pomalidomide, and dexamethasone (KPd).

Phase 1 of the study will enroll up to 12 patients to evaluate the toxicity of TP combination therapy. It will also establish the pomalidomide dose to be used in phase 2.

Phase 2 will enroll 150 patients who will be randomized to receive either TP or KPd. Researchers will assess which approach is more effective by using a bone marrow test taken after 9 cycles of treatment. The test will detect any microscopic traces of cancer cells that might remain. They will compare the number of patients in each group who achieve a result where no cancer cells can be found, known as a minimal residual disease-negative (MRD-) complete response.

Patients are eligible for this study if they have experienced a relapse of their multiple myeloma after one course of treatment that includes lenalidomide. They must also have previously received daratumumab or isatuximab. Patients must not have had more than two prior courses of therapy for their myeloma (induction +/- stem cell transplant + maintenance equals one course). During the study, they must not receive chemotherapy or take part in any other research treatment.

The study chair for this trial is Murali Janakiram, MD (City of Hope Comprehensive Cancer Center), and the co-chair is Ajay Kumar Nooka, MD (Emory University/Winship Cancer Institute). The community co-chair is Natasha Edwin, MD (Providence Saint Vincent Medical Center).