Phase 3 Trial Will Assess Darzalex-containing Combo Therapy in Multiple Myeloma Patients

The anti-CD38 agent Darzalex (daratumumab) will be investigated in a Phase 3 clinical trial in combination with Kyprolis (carfilzomib) and Decadron (dexamethasone) in relapsed/refractory multiple myeloma patients.

The study will be conducted under a collaboration and supply agreement between Genmab, Janssen Biotech, and Onyx Pharmaceuticals (a subsidiary of Amgen), which also covers all potential studies evaluating the combination of Darzalex and Kyprolis in cancer patients.

According to estimates from the American Cancer Society, approximately 30,330 new multiple myeloma cases will be diagnosed in 2016 in the U.S. alone, and 12,650 are expected to die from the disease. Patients are commonly treated with proteasome inhibitors, such as Kyprolis or Velcade (bortezomib), or immunomodulatory agents, such as Revlimid (lenalidomine) and Pomalyst (pomalidomide).

However, patients often relapse, and those who are refractory to both lines of therapy have a poor prognosis and few treatment options.

Darzalex has emerged as a promising drug to treat those patients. It is approved in the U.S. for patients who have received at least three prior lines of therapy, including a proteasome inhibitor and an immunomodulatory agent, and consists of a monoclonal antibody that binds selectively to the CD38 molecule, widely expressed in myeloma cells.

Darzalex can not only induce tumor cell death directly by activating their programmed cell death pathways, but also indirectly, by promoting a targeted immune response to cells expressing the CD38 molecule. It also results in the reduction of suppressive immune cells, like myeloid-derived suppressor cells, regulatory T-cells, and regulatory B-cells (all of which express CD38), enhancing the cytotoxic activity of tumor-killing T-cells.

The new randomized, open-label Phase 3 clinical trial will seek to determine whether combining Darzalex with Kyprolis and Decadron improves progression-free survival of multiple myeloma patients who have already received one to three prior therapies. The study, which is expected to start dosing patients in 2017, will enroll a total of 450 patients.

“The new Phase 3 study combining daratumumab with carfilzomib and dexamethasone is an exciting addition to the broad and expansive development program for daratumumab and illustrates the strategy to explore as many clinical development opportunities for daratumumab as possible, and potentially establish daratumumab as the backbone treatment in multiple myeloma,” Jan van de Winkel, PhD, CEO of Genmab, said in a news release.

An ongoing Phase 1 trial (MMY1001; NCT01998971) is also evaluating Darzalex in combination with a number of backbone myeloma therapies, including Kyprolis, in both newly diagnosed and relapsed/refractory multiple myeloma patients. The trial is part of an earlier collaboration agreement between Janssen and Amgen.