Similar Efficacy and Safety Seen Between Under-the-Skin Formulation and Intravenous Darzalex for Myeloma, Phase 3 Trial Shows

An under-the-skin formulation of daratumumab is as effective as its intravenous delivery — marketed as Darzalex — at easing tumor burden and has comparable safety in adults with relapsed or refractory multiple myeloma, according to a Phase 3 trial.

Trial results were presented in a study, “Efficacy and safety of the randomized, open-label, non-inferiority, phase 3 study of subcutaneous (SC) versus intravenous (IV) daratumumab (DARA) administration in patients (pts) with relapsed or refractory multiple myeloma (RRMM): COLUMBA,” at the recent 2019 American Society of Clinical Oncology (ASCO) Annual Meeting, and was selected for the Best of ASCO highlights.

Darzalex is an antibody that targets the CD38 protein, widely produced by multiple myeloma cells. The therapy induces cell death and activates immune processes that help eliminate these cells.

A total of 522 patients at a median age of 67 years participated in the open-label, multicenter COLUMBA trial (NCT03277105). In line with Darzalex’s approved indications in the U.S., all patients had received at least three prior lines of treatment, including a proteasome inhibitor and an immunomodulator, or did not respond to both of these types of therapy.

Two groups were compared: 263 patients received 1,800 mg of Janssen’s daratumumab and 2,000 units per milliliter (U/ml) of recombinant human hyaluronidaser (HuPH20) via subcutaneous (under-the-skin) delivery. Additionally, 259 patients received intravenous (into-the-vein) Darzalex at 16 mg/kg. Treatment was given once per week in cycles 1–2, every two weeks in cycles 3–6, and every four weeks in cycle 7 and thereafter. Each cycle lasted 28 days.

In line with prior reports, the results showed that, after a median follow-up of 7.5 months, the overall response rate — the proportion of patients responding partially or completely to treatment — was 41% with the subcutaneous formulation and 37% with Darzalex. A similar response rate was seen across all clinically relevant subgroups.

Progression-free survival — the time until cancer progression during or after treatment — was similar between the two delivery routes — 5.6 months with subcutaneous versus 6.1 months with intravenous — as was the therapy’s trough concentration, which refers to its lowest dose before the next dose is administered.

The median duration of each subcutaneous injection was five minutes, compared with more than three hours with intravenous infusions.

“This study … offers the potential for a fixed-dose administration, shorter infusion times and a lower rate of infusion-related reactions,” Maria-Victoria Mateos, MD, PhD, COLUMBA’s primary investigator, said in a press release.

“Daratumumab IV has proven to be an important medication in the treatment of multiple myeloma, and a new subcutaneous formulation may offer patients a different experience, including a shorter administration time,” added Mateos, who is the director of the myeloma unit at University Hospital of Salamanca-IBSAL in Spain.

The most frequent serious or life-threatening treatment-emergent adverse events with the subcutaneous formulation and with intravenous Darzalex were low platelet counts (14% in both groups), anemia (13% vs. 14%) and reduced levels of neutrophils (13% vs. 8%). The group receiving subcutaneous treatment had a significantly lower rate of infusion-related reactions (13% vs. 35%).

The main reasons for patients stopping treatment were disease progression (43% in the subcutaneous group vs. 44% in the intravenous group) and adverse events (7% vs. 8%).

“We are always exploring new ways to help patients, and these compelling findings reinforce the potential for a new route of administration for Darzalex,” said Mark Wildgust, PhD, Janssen Research & Development‘s vice president of global medical affairs, oncology. “We look forward to pursuing regulatory submissions for this formulation and hopefully expanding the reach of Darzalex for patients who may be candidates for this novel formulation.”