As promised, here are details from a preliminary study showing impressive response rates when Darzalex (daratumumab) is combined with Revlimid and dexamethasone.
Similarly impressive numbers were also achieved when the immunotherapy drug was used along with pomalidomide. I’ll pass along those details later today after that data is presented.
Back to Darzalex and Revlimid. Very early Phase 1/2 findings show that the human CD38-directed monoclonal antibody (mAb) Darzalex (daratumumab) in combination with Revlimid (lenalidomide) and dex demonstrated an overall response rate (ORR) of 81 percent in relapsed or refractory multiple myeloma patients who had received a median of two prior therapies. After 18 months of treatment, investigators observed an overall survival (OS) rate of 90 percent, with 72 percent of patients experiencing progression-free survival (PFS).
On the surface, one might question these numbers. Two prior therapies? The bar wasn’t set very high. And point of fact, early trials like these are focused on dosing safety.
But this is where my interview with Dr. Tahamtan Ahmadi yesterday comes into play. Dr. Ahmadi assured me that he’s seen data that’s almost as impressive in patients that are heavily pretreated and refractory to IMiDs, proteasome inhibitors or both.
Here’s Janssen’s official press release about this morning’s presentation:
Daratumumab (DARZALEX™) Combined with Standard Treatment for Multiple Myeloma Produced Deep and Durable Responses in Relapsed or Refractory Patients
Results from GEN503 trial featured in official press program at the 57th Annual American Society of Hematology Meeting and Exposition
ORLANDO, FL and RARITAN, NJ, DECEMBER 6, 2015 – Janssen Research & Development, LLC announced new data from the ongoing Phase 1/2 GEN503 investigational study showing the human CD38-directed monoclonal antibody daratumumab (DARZALEX™), in combination with lenalidomide and dexamethasone, yielded an overall response rate (ORR) of 81 percent in relapsed or refractory multiple myeloma patients who had received a median of two prior therapies.
After 18 months of treatment, investigators observed an overall survival (OS) rate of 90 percent, with 72 percent of patients experiencing progression-free survival (PFS).1 The data, from the part 2 cohort expansion phase of GEN503, were presented today during the official press program at the 57th Annual American Society of Hematology (ASH) Meeting and Exposition in Orlando, FL and will be presented in full during an oral abstract session on Monday, December 7 at 7:30 a.m. Eastern Time (ET).
“Daratumumab has already shown pronounced activity as a single-agent immunotherapy in a heavily pre-treated patient population with relapsed or refractory multiple myeloma. These findings suggest that it has the potential to induce rapid, deep, and durable responses in combination with standard treatment in earlier lines of therapy,” said lead study author, Torben Plesner, M.D., Vejle Hospital, Vejle, Denmark. “These data are particularly exciting, as 72 percent of patients treated with daratumumab combination therapy did not progress or relapse after 18 months of treatment.”
The cohort expansion phase of the open-label, international, multicenter, dose escalating Phase 1/2 GEN503 study enrolled 32 patients who had received a median of two prior lines of therapy. Stringent complete response (sCR) was reported in 25 percent of patients (n=8), complete response (CR) was reported in 9 percent (n=3), very good partial response (VGPR) was reported in 28 percent (n=9), and partial response (PR) was reported in 19 percent (n=6). Among all patients, the median times to first and best response were one month (95 percent confidence interval [CI], 0.5-5.6) and 5.1 months (95 percent CI, 0.5-14.4), respectively. The median duration of response was not reached.1
“With daratumumab we sought to introduce a new immunotherapy approach to treating multiple myeloma through several, immune-mediated mechanisms of action that could redefine the treatment paradigm for certain patients. These preliminary findings reaffirmed our strong belief in the potential for daratumumab and led us to further evaluate this combination in relapsed or refractory and newly diagnosed multiple myeloma patients in the now ongoing POLLUX and MAIA Phase 3 studies,” said Peter F. Lebowitz, M.D., Ph.D., Global Oncology Head, Janssen Research & Development. “We are looking forward to seeing the full results of these and other trials from our robust clinical program, which will help unlock the full potential of the first approved human CD38-directed monoclonal antibody as both a single agent and in combination with standard treatment.”
The two-part GEN503 study is comprised of a dose escalation study (part 1) and a cohort expansion study (part 2). In part 1, patients received daratumumab in combination with lenalidomide (25 mg orally on days 1 through 21 of every 28-day cycle) and dexamethasone (40 mg intravenously and orally once weekly). Daratumumab 2-16 mg/kg body weight was administered as an intravenous infusion given weekly for the first eight weeks, then bi-weekly (every two weeks) for the next 16 weeks, and then monthly until disease progression or unmanageable toxicity for 24 months in total. In part 2, all patients were administered the recommended Phase 2 daratumumab dose (16 mg/kg), patients refractory to lenalidomide were excluded, and patients with at least one prior line of therapy were included.
In this study, the most common adverse events (AEs) included neutropenia (84 percent), cough (47 percent), muscle spasms (44 percent) and diarrhea (44 percent). Fifty percent of patients experienced serious AEs, but only neutropenia (n=3), gastroenteritis (n=2) and pyrexia (n=2) occurred in more than one patient. Eighteen patients (56 percent) had infusion reactions; these were generally mild to moderate (Grade ≤2) and usually occurred during the first infusion. Infusion reactions were managed with pre-medication or by slowing infusion rate. No additional safety signals were observed.
I’d better keep moving. More news to follow.
Feel good and keep smiling! Pat