Darzalex Add-on Increases Complete Responses After Stem Cell Transplant, Phase 3 Myeloma Trial Shows

Adding Darzalex (daratumumab) to the standard pre-transplant therapy for multiple myeloma significantly increased the number of patients showing no signs of cancer after a stem cell transplant, a Phase 3 trial shows.

The open-label, multicenter study, called CASSIOPEIA (NCT02541383), was designed to test Genmab‘s Darzalex in multiple myeloma patients who had not received any prior treatment but were eligible for an autologous stem cell transplant (ASCT) — a procedure where patients receive a transplant of their own blood stem cells after being treated with high doses of chemotherapy.

The trial, which enrolled 1,085 patients, is being conducted in two parts. In part one, researchers tested if Darzalex plus standard high-dose chemotherapy — Velcade (bortezomib), thalidomide, and dexamethasone (collectively known as VTD) — was better than VTD alone at eliminating traces of cancer.

Patients were randomly assigned four cycles of either Darzalex plus VTD or VTD alone, as an induction therapy. All patients then received an ASCT, followed by a consolidation therapy with two cycles of either Darzalex plus VTD or VTD alone.

The primary objective for the first part of the study was to determine the number of patients achieving a stringent complete response (sCR), defined as no signs of cancer cells or myeloma antibodies, after induction and consolidation therapy.

According to the trial data, 28.9% of the patients treated with Darzalex in combination with VTD achieved sCR, whereas only 20.3% of the patients receiving just VTD as a front-line treatment reached the same outcome.

“Having previously seen positive data in the ALCYONE trial, for the frontline treatment of patients ineligible for autologous stem cell transplant, we are very pleased to see the results from the CASSIOPEIA study, which presents exciting insights into the potential of daratumumab for newly diagnosed multiple myeloma patients who received an autologous stem cell transplantation (ASCT),” Jan van de Winkel, PhD, the CEO of Genmab, said in a press release.

In the second part of the study, all patients who responded to the combination therapy were re-assigned to receive either maintenance treatment with Darzalex every eight weeks for up to two years, or will be kept on observation with no further treatment.

“We also look forward to the data from the second part of the study, which will provide further data on the impact of daratumumab monotherapy as maintenance treatment,” van de Winkel said.

Safety analysis also revealed the safety profile of Darzalex in combination with VTD was consistent with what had previously been reported for VTD and Darzalex alone.

Further analysis of the safety and efficacy data from the combination therapy of Darzalex with VTD is still ongoing. Janssen Pharmaceuticals, who obtained the license to develop and commercialize Darzalex from Genmab in 2012, is planning to discuss regulatory submissions for this indication with health authorities.

The trial’s sponsors — the French Intergroupe Francophone du Myelome in collaboration with the Dutch-Belgian Cooperative Trial Group for Hematology Oncology — are also planning to submit additional data for presentation at an upcoming medical conference and for future publication in a peer-reviewed journal.