Darzalex Faspro Combo Shows Benefits for Relapsed, Refractory Myeloma in Phase 3 Trial

Marisa Wexler MS avatar

by Marisa Wexler MS |

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Darzalex Faspro (daratumumab and hyaluronidase) significantly extended the time people with relapsed or refractory multiple myeloma live without disease worsening, when added to a combination of Pomalyst (pomalidomide) and dexamethasone, a Phase 3 clinical trial shows.

Darzalex Faspro is a subcutaneous, or under-the-skin, formulation of Janssen‘s Darzalex (daratumumab), which is administered intravenously (into the vein).

The randomized APOLLO trial (NCT03180736) included patients who had received at least one prior line of therapy, including the immunomodulatory therapy Revlimid (lenalidomide) and a proteasome inhibitor. The recent findings are anticipated to support the use of Darzalex Faspro for this patient population, for whom the subcutaneous formulation is not yet approved.

“We are pleased with these positive results for daratumumab, administered as a subcutaneous formulation, in combination with pomalidomide and dexamethasone,” Jan van de Winkel, PhD, CEO of Genmab said in a press release.

Darzalex is an antibody designed to recognize and block the activity of CD38, a protein found on the surface of myeloma cells, to prevent their growth and eliminate them. It was originally developed by Genmab and then licensed to Janssen in 2012.

Compared with intravenous Darzalex, the subcutaneous formulation requires markedly less expertise to do safely and takes minutes rather than hours, so it has been billed as a faster and easier alternative to the original.

Subcutaneous Darzalex was recently approved in the European Union for all the same indications as the intravenous formulation. In the U.S., Darzalex Faspro was also approved, but only for four of Darzalex’s six indications.

Notably, the use of Darzalex Faspro in combination with the oral immunomodulatory treatment Pomalyst and the corticosteroid dexamethasone was not covered in the FDA approval, although the intravenous formulation is approved for use in combination with these medications.

APOLLO, sponsored by the European Myeloma Network in collaboration with Janssen, included 304 myeloma patients who had previously been treated with Revlimid and a proteasome inhibitor.

Participants were randomly assigned to treatment with Pomalyst and dexamethasone alone, or to a triple combination containing Darzalex Faspro in addition to the other two medications.

In the study’s original design, participants randomized to the triple combination were given the intravenous formulation, Darzalex. However, the study design was amended such that newly enrolled participants were instead given the subcutaneous version. Participants who enrolled prior to this change were given the option to switch to the subcutaneous formulation.

APOLLO’s main goal is to determine whether Darzalex Faspro extends the time during which patients remain alive and without evidence of disease progression, a measure called progression-free survival.

Secondary measures include the proportion of patients responding to treatment, number of patients achieving minimal residual disease negativity (the absence of a small number of myeloma cells that can cause the cancer to reappear), duration of responses, safety, and quality of life.

According to the top-line results, APOLLO met its primary goal, with patients living significantly longer without evidence of disease progression on the Darzalex Faspro triple combo, compared with those on Pomalyst and dexamethasone only.

The safety profile of the combination was consistent with those of each therapy separately, Genmab also reported.

Janssen is now planning to discuss the results with relevant authorities in preparation for regulatory submissions. Detailed results will be presented at upcoming medical conferences.