Updated results of a key Phase 1/2 trial testing the poten­tial new myeloma ther­a­py daratumumab were released this morning. The new results con­firm pre­vi­ous research indicating that single-agent dara­tu­mu­mab has notable activity as a multiple myeloma ther­apy.

Specifically, the results show that nearly one third of the trial par­tic­i­pants – who had received a median of five prior ther­a­pies – responded to single-agent dara­tumumab. The median time to disease pro­gres­sion was 3.7 months, and the esti­mated one-year over­all survival rate was 65 per­cent.

Daratumumab’s safety profile in the trial was favorable. Only 5 per­cent of patients in the study, for example, dis­con­tinued treat­ment due to side effects from the drug.

The new dara­tu­mu­mab results were made public this morning when the embargo was lifted on an abstract summarizing the study data. A detailed report of the results will be made during an oral presentation session on Tuesday, June 2, at the annual meeting of the American Society of Clinical Oncology (ASCO).

(Update - June 3, 2015 - The slides [PDF] for the oral presentation of the dara­tu­mu­mab results at the ASCO meeting are now avail­able to the Beacon's readers, courtesy of Dr. Sagar Lonial, who gave the presentation.)

Earlier this month, Johnson & Johnson (NYSE:JNJ) announced plans to file appli­ca­tions by the end of this year for U.S. and European regu­la­tory approval of dara­tu­mu­mab as a new treat­ment for re­lapsed multiple myeloma. The updated trial results released this morning will sup­port those appli­ca­tions, which could result in dara­tu­mu­mab becoming avail­able to treat myeloma patients outside of clin­i­cal trials by the first half of next year.

Johnson & Johnson is devel­op­ing dara­tu­mu­mab in col­lab­o­ration with the Danish bio­technology com­pany Genmab.  The drug is cur­rently being tested in a num­ber of multiple myeloma clin­i­cal trials, involving both newly diag­nosed and re­lapsed patients.

Background

Daratumumab is a mono­clonal anti­body that binds to a protein known as CD38, which is commonly found on the surface of myeloma cells. Once bound to a myeloma cell, dara­tu­mu­mab then attacks the cell while also signaling the patient's immune sys­tem to act against the cells.

Two other CD38 mono­clonal anti­bodies are also under devel­op­ment as poten­tial myeloma ther­a­pies: SAR650984 and MOR202. In addi­tion, elotuzumab, a mono­clonal anti­body that targets a dif­fer­en­t protein found on myeloma cells, is also being in­ves­ti­gated as a poten­tial myeloma ther­apy.  Important data about elotuzumab's efficacy and safety as a myeloma ther­apy also will be presented at the ASCO meeting next Tuesday.

Daratumumab was granted granted breakthrough ther­apy desig­na­tion by the the U.S. Food and Drug Ad­min­istration in 2013 (see related Beacon news). Break­through ther­apy desig­na­tion is designed to acceler­ate the devel­op­ment and review process for drugs in­tended to treat serious or life-threatening illnesses.

Study Design

The Phase 1 part of the dara­tu­mu­mab trial in­cluded 34 patients who were ran­domly assigned to receive either 8 mg/kg of dara­tu­mu­mab every four weeks or 16 mg/kg of dara­tu­mu­mab at weekly in­ter­vals for 8 weeks, then every 2 weeks for an addi­tional 16 weeks, then every 4 weeks there­after.

Subsequently, 90 addi­tional patients were recruited for the 16 mg/kg dara­tu­mu­mab treat­ment group for the Phase 2 part of the trial.

The updated results released this morning are for the 106 patients in both parts of the study who received the 16 mg/kg dara­tu­mu­mab dose.

The median time since diag­nosis for the 106 patient was 4.8 years, and the patients had received a median of five prior ther­apy. Almost all of the patients (96 per­cent) were resistant (refractory) to their last line of ther­a­py, and almost all patients (95 per­cent) received either a pro­te­a­some inhibitor or an immuno­modu­la­tory agent as their last treat­ment. Almost two thirds of the patients (63 per­cent) were pre­vi­ously treated with Poma­lyst (poma­lido­mide), and almost half (48 per­cent) had been treated at some point with Kyprolis (car­filz­o­mib).

Study Results

Overall, 29 per­cent of patients responded to single-agent dara­tu­mu­mab, with 3 per­cent achieving a com­plete response, 9 per­cent a very good partial response, and 17 per­cent a partial response. The median time to pro­gres­sion was 3.7 months. The median over­all survival has not been reached, and the esti­mated 1-year OS rate is 65 per­cent.

After a median follow-up time of 9.4 months, 45 per­cent of the patients who have responded to dara­tu­mu­mab treat­ment remain on ther­apy.

The most common side effects in­cluded in­fusion-related reac­tions (45 per­cent), which typically occurred early in the course of treat­ment, fatigue (40 per­cent), anemia (33 per­cent), nausea (29 per­cent), throm­bo­cyto­penia (26 per­cent), back pain (23 per­cent), and neu­tro­penia (23 per­cent). The treat­ment dis­con­tinu­a­tion rate due to adverse events was 5 per­cent.

The response rate seen in the dara­tu­mu­mab trial is slightly higher than the 23 per­cent response rate seen in the Phase 2 clin­i­cal trial that eventually led to the approval of Kyprolis in the United States (see related Beacon news article). The Kyprolis trial also was a single-agent study, and it also involved re­lapsed mye­lo­ma patients who had received a median of five prior ther­a­pies.

The pro­gres­sion-free survival and over­all survival out­comes reported this morning for the dara­tu­mu­mab trial are very similar to those seen in the Kyprolis trial.

For more in­for­ma­tion, please see the related abstract #LBA8512 at the ASCO meeting.