Darzalex Delays Disease Progression After ASCT, Phase 3 Trial Reports

First-line maintenance therapy with Darzalex (daratumumab) significantly delays disease progression or death in adults with multiple myeloma who responded to autologous stem cell transplant (ASCT), according to data from the CASSIOPEIA trial’s second part.

These findings, from a pre-planned interim analysis conducted by an independent data monitoring committee, indicate that the Phase 3 trial met the main goals of both its first and second part. As such, the committee recommended unblinding study results, making them known to participants and involved researchers.

“Following the positive data from the first part of the CASSIOPEIA study, we are very pleased to see this benefit,” Jan van de Winkel, PhD, CEO of Genmab, the original creator of Darzalex, said in a press release.

Janssen Biotech, which licensed Darzalex from Genmab in 2012, plans to discuss with health authorities the potential submission of an application seeking Darzalex’s approval for this indication. It also plans to submit the data to an upcoming medical conference and for publication in a peer-reviewed journal.

Darzalex is an antibody that binds to and blocks the activity of CD38, a protein found at high levels on the surface of myeloma cells, regardless of disease severity. When bound to its target, Darzalex is thought to directly kill cancer cells and trigger immune responses against them, leading to rapid tumor cell death.

The open-label, multicenter, two-part CASSIOPEIA study (NCT02541383) was designed to evaluate the safety and effectiveness of adding Darzalex to standard pre-transplant therapy in a group of untreated multiple myeloma patients who were eligible for an ASCT.

In part one, 1,085 participants were randomly assigned to either a combination of Darzalex with standard high-dose chemotherapy — Velcade (bortezomib), thalidomide, and dexamethasone (collectively known as VTd) — or VTd alone, as induction (pre-transplant) and consolidation (post-transplant) treatment.

Its main goal was to determine whether the Darzalex-VTd combo was superior to VTd alone at eliminating any traces of cancer, as assessed through rates of stringent complete responses — no signs of cancer cells or myeloma antibodies.

Top-line data from this first part showed that goal was met, as a significantly greater proportion of patients treated with the Darzalex combo (28.9%) achieved stringent complete responses following ASCT, compared with those on VTd alone (20.3%).

In addition, at a median follow-up of 18.8 months, the Darzalex combo significantly lowered the risk of disease progression or death by 53%, and increased the percentage of patients achieving at least complete (39% vs. 26%) or very good partial (83% vs. 78%) responses compared with VTd alone.

Patients who responded at least partly to ASCT were included in the study’s second part, in which they were re-assigned to receive either maintenance treatment with Darzalex every eight weeks for up to two years, or to no further treatment and kept on observation.

Its main goal was to assess whether Darzalex maintenance treatment extended the time patients lived without signs of disease progression. The newly announced data show that the therapy reduced the risk of progression or death by 47%, compared with no maintenance treatment, meeting this second part’s main endpoint.

The safety profile of Darzalex in the trial’s second part was consistent with its known safety profile, with no new concerns identified.

CASSIOPEIA, expected to conclude in August 2024, is being conducted by the French Intergroupe Francophone du Myelome (IFM), in collaboration with the Dutch-Belgian Cooperative Trial Group for Hematology Oncology (HOVON) and Janssen Research & Development.

“We are appreciative of the efforts of the IFM, of HOVON and of Janssen for their work on this study,” van de Winkel said.

Based on the positive findings from CASSIOPEIA’s first part, the Darzalex-VTd combination therapy was approved in the U.S. and in Europe for adults with newly diagnosed multiple myeloma who are eligible for ASCT.