Janssen Biotech is planning a new Phase 3 clinical trial to explore a combination of under-the-skin daratumumab plus Revlimid (lenalidomide) as a maintenance treatment for multiple myeloma patients who received an autologous stem cell transplant as front-line treatment.
Specifically, the study is for patients who are positive for minimal residual disease (MRD) after their stem cell transplant, meaning they still have small numbers of cancer cells in their bone marrow.
Daratumumab is an approved myeloma treatment that targets the CD38 protein, widely produced by multiple myeloma cells. When bound to its target, daratumumab not only causes cells to die directly, but also activates immune-dependent processes that help eliminate cancer cells.
The treatment, originally developed by Genmab and licensed to Janssen in 2012, is sold as an intravenous treatment called Darzalex. But Janssen has been developing an under-the-skin formulation of daratumumab that is showing similar efficacy as its intravenous counterpart.
Now, the company set out to examine whether adding this daratumumab formulation to standard Revlimid maintenance after a stem cell transplant could increase the amount of patients achieving minimal residual disease negativity.
The standard of care for fit multiple myeloma patients is to receive high-dose chemotherapy followed by an autologous stem cell transplant after completion of induction therapy. Autologous stem cell transplant — a procedure that involves collecting a patient’s blood stem cells before treatment and transplanting them afterward to produce new and healthy blood cells — can provide significant remission that is both long and deep, extending survival.
However, after a temporary remission, it is common that patients relapse, often due to the presence of a small but clinically relevant number of multiple myeloma cells — a condition called minimal residual disease — undetected by traditional techniques.
Maintenance treatments that eliminate these vestigial cancer cells are thus required to extend remission and survival.
The upcoming Phase 3 trial, called AURIGA (NCT03901963), is expected to include 214 myeloma patients across 22 clinical sites in the U.S. Participants must be newly diagnosed, be minimal residual disease-positive after a frontline stem cell transplant, and have not received prior treatment with a CD38 inhibitor.
Patients will be randomly assigned subcutaneous daratumumab — given once a week in the first 28-day cycles, once every two weeks through cycles 3 to 6, and every four weeks thereafter — plus standard Revlimid — given orally, once a day — or Revlimid only.
AURIGA’s main goal is to determine whether more patients on daratumumab achieve a negative status for minimal residual disease within one year. This is defined as having fewer than 10 cancer cells per million cells in the bone marrow, and will be evaluated by next-generation sequencing, a sensitive molecular technology that can detect cancer cells at levels below the limits of traditional strategies.
Secondary measures include the time patients live without disease worsening, number of patients with durable minimal residual disease negativity, percentage of patients achieving a complete response, overall survival, quality of life measures, and safety.
The trial is expected to begin by mid-2019. For more information about contacts and locations, go here.