Daratumumab con­tinues to show promise for re­lapsed and refractory multiple myeloma patients. Results from a Phase 1/2 study indicate that dara­tu­mu­mab may be effective and safe in heavily pre­treated patients.

In particular, dara­tu­mu­mab's activity as an anti-myeloma agent seems at least as good as that of the newest myeloma ther­a­pies.

“The response to dara­tu­mu­mab was accompanied by the clearance of myeloma cells,” said Dr. Torben Plesner from the Vejle Hospital in Denmark, who presented the findings from the dara­tu­mu­mab trial at the 2012 American Society of Hematology (ASH) meeting last month.

“Daratumumab has shown a favorable safety profile as a [single-agent ther­apy],” he added.

However, Dr. Plesner noted that the maximum tolerated dose of dara­tu­mu­mab had not been reached yet, and further trials are needed to assess its effectiveness in com­bi­na­tion with other drugs.

Daratumumab is being devel­oped by the Danish pharma­ceu­tical com­pany Genmab together with Janssen Biotech, a Johnson & Johnson (NYSE: JNJ) sub­sid­i­ary.  The med­i­cine is a mono­clonal anti­body, a class of drugs that in­cludes two other poten­tial new myeloma treat­ments, elotuzumab ^[1] and siltuximab ^[2].

Daratumumab binds to the CD38 molecule, which is found on the surface of multiple myeloma and other blood cancer cells.  Once dara­tu­mu­mab is bound to the CD38 molecule on cancer cells, it signals for the immune sys­tem to kill the cells.

Initial results of the current trial, which Dr. Plesner presented at the American Society of Clinical Oncology Meeting in June 2012, showed that 24 per­cent of patients had achieved a partial response to dara­tu­mu­mab (see related Beacon ^[3] news).

The updated findings that Dr. Plesner presented at ASH were based on data from 32 heavily pre­treated myeloma patients who were in­eli­gible for stem cell trans­plan­ta­tion. Patients had received a median of six prior ther­a­pies. The median patient age was 61 years.

All patients had pre­vi­ously been treated with Velcade ^[4] (bor­tez­o­mib), and 90 per­cent of patients had also received Revlimid ^[5] (lena­lido­mide).

Patients received varying doses of dara­tu­mu­mab, ranging from 0.005 mg/kg up to 24 mg/kg for eight weeks.

Overall, 47 per­cent of the patients ex­peri­enced a reduction in M-protein levels in the blood or urine, which corresponded to the fol­low­ing response rates: 12.5 per­cent of patients achieved a partial response, 19 per­cent a minor response, and 16 per­cent stable disease,

Dr. Plesner emphasized that dara­tu­mu­mab was more effective at lowering M-protein levels when admin­istered at higher doses.

“At doses of 4 mg/kg and above, 67 per­cent of patients had a least a minimal response,” he explained.

Dr. Plesner added that “the pro­gres­sion-free survival also in­creased with longer exposure to dara­tu­mu­mab.”

Daratumumab's activity against myeloma in this early-stage trial compares favorably with what was observed in the initial dose-ranging trials for Kyprolis ^[6] (carfilzomib ^[7]), the most recently approved anti-myeloma ther­apy.

In the part of the Kyprolis trial (results ^[8]; PDF) using the drug's current dosing schedule, a slightly higher share of the relevant patients (17 per­cent versus 12.5 per­cent for dara­tu­mu­mab) achieved a partial response.  However, more patients in the dara­tu­mu­mab trial (47 per­cent versus 38 per­cent for Kyprolis) ex­peri­enced stable disease or better.

Moreover, the patients in the Kyprolis trial were not quite as heavily pre­treated as those in the dara­tu­mu­mab trial.

According to Dr. Plesner, dara­tu­mu­mab also has dem­onstrated a favorable safety profile in its trial. “Daratumumab was surprisingly well tolerated,” he said during his ASH presentation.

Most of dara­tu­mu­mab's side effects were in­fusion-related, occurring within three to four hours of the in­fusion.

The most commonly observed severe side effects in­cluded dif­fi­culty breathing (3 per­cent), low blood cell counts (3 per­cent), and elevated liver enzymes (3 per­cent).

Going for­ward, Dr. Plesner and his colleagues plan to study the 8 mg/kg dose of dara­tu­mu­mab as a single-agent ther­apy and in com­bi­na­tion with other drugs.

For more in­for­ma­tion, please refer to abstract 73 ^[9] on the ASH 2012 meeting website, as well as Dr. Plesner’s presentation slides ^[10], which he has made avail­able for download and viewing as a courtesy to the Beacon’s readers. For more in­for­ma­tion re­gard­ing clin­i­cal trials studying dara­tu­mu­mab, please visit the clinicaltrials.gov ^[11] website.