Under-the-skin Formulation as Effective as Intravenous Darzalex for Myeloma Patients, Study Says

An under-the-skin injection of daratumumab is as effective as its intravenous formulation, Darzalex (daratumumab), at reducing tumor burden in multiple myeloma patients, a Phase 3 clinical trial shows. The new formulation also led to similar levels of daratumumab in circulation, meeting the trial’s co-primary goals, according to Genmab, the treatment’s developer.

Janssen Biotech, which licensed Darzalex from Genmab in 2012, will now discuss the use of this easy-to-administer formulation with health authorities. Full data from the trial soon will be presented at a medical conference.

Darzalex is an antibody that targets the CD38 protein, which is widely produced by multiple myeloma cells. When bound to its target, Darzalex not only causes cells to die directly, but also activates immune-dependent processes that help eliminate cancer cells.

The treatment is approved in the U.S. for four multiple myeloma indications, including as a single agent for patients who received at least three prior lines of therapy, including a proteasome inhibitor like Velcade (bortezomib), and an immunomodulatory agent such as Revlimid (lenalidomide), or those who failed to respond to a proteasome inhibitor and an immunomodulatory agent.

The treatment is given as an intravenous infusion, but a Phase 1 trial in relapsed or refractory myeloma patients (NCT02519452) has shown that a co-formulation of daratumumab plus recombinant human hyaluronidase (rHuPH20) was well-tolerated and led to similar response rates as those seen in other Darzalex trials.

Janssen designed the COLUMBA Phase 3 trial (NCT03277105) to determine if this co-formulation was non-inferior to intravenous Darzalex for the treatment of multiple myeloma patients.

The trial, still recruiting participants, is for patients who failed three or more prior lines of therapy, including a proteasome inhibitor and an immunomodulatory agent, or who have not responded to either of those treatments.

To date, 522 patients were included and randomly assigned subcutaneous daratumumab (1,800 mg) with rHuPH20 2000 (U/mL, or units per milliliter) or intravenous Darzalex (16 mg/kg). Treatment was given weekly in the first two four-week cycles, once every two weeks in cycles 3 to 6, and once every four weeks thereafter until end of study, disease progression, or unacceptable toxicity.

COLUMBA’s primary goals are to determine if the subcutaneous formulation leads to an overall response rate — the proportion of patients responding partially or completely to treatment — at least as good as intravenous Darzalex, and that the levels of daratumumab in circulation before the first injection of cycle 3 also is non-inferior to that seen with Darzalex.

Secondary goals include the proportion of patients experiencing infusion-related reactions, the time to disease progression or death, duration of response, time to next treatment, and overall survival.

Genmab now reports that both co-primary goals have been met, with a similar proportion of patients responding to the subcutaneous co-formulation (41.1%) and the intravenous formulation (37.1%), and with both approaches leading to comparable daratumumab levels in circulation before cycle 3 began  — 499 mg/mL versus 463 mg/mL.

“With the data from each of the key clinical studies we learn more about the difference that daratumumab potentially can make to the lives of patients suffering with multiple myeloma,” Jan van de Winkel, PhD, chief executive officer of Genmab, said in a press release.

“I am particularly excited about the results from this study as it may support a much quicker and far more convenient administration of daratumumab, which would provide an important benefit for many patients and their families,” he said.