HuMax-CD38™ is a fully human IgG1,κ antibody in development to treat multiple myeloma (MM).  HuMax-CD38 targets the CD38 molecule which is very highly expressed on the surface of multiple myeloma cells.  The antibody was selected from a large panel of antibodies based on its ability to bind to and kill multiple myeloma tumor cells.

Multiple Myeloma   

Multiple myeloma is a cancer of plasma cells and accounts for approximately 1% of all cancers.  The incidence of multiple myeloma is 5.2 per 100,000 people, corresponding to 15,270 new cases in the US in 2004.  Approximately 11,000 deaths in the US each year are related to multiple myeloma and the estimated number of new cases is rising.  At present, no cure is available, and the mean survival is approximately 3-5 years from the time of diagnosis.

Ongoing Clinical Studies

Phase I/II Study
Genmab is conducting a Phase I/II safety and dose finding study of HuMax-CD38 for the treatment of multiple myeloma.  The study will include a maximum of 122 patients with MM who are relapsed or refractory to at least two different prior treatments and are without further established treatment options. 

The open label dose escalation saftey study will consist of two parts.  In Part 1, 26 to 62 patients will be enrolled depending on the number of dose levels reached during escalation.  Patients in Part 1 will be divided into cohorts at various doses of HuMax-CD38, with each patient receiving 7 infusions.  The first infusion will be followed by a 3 week period of safety monitoring with the following 6 doses to be given at weekly intervals.

In Part 2, 60 patients will be enrolled with 20 patients in each of three dose levels.  The highest dose in Part 2 will be the highest safe dose in Part 1 and two dose levels below.  Patients in Part 2 will receive 6 infusions of HuMax-CD38 at weekly intervals.

In each part of the study, patients will attend 12 follow up visits at 2 to 4 week intervals to assess saftey and efficacy and will be followed every 12 weeks thereafter until disease progression, initiation of alternative treatment for MM or death for a maximum of 2 years from study start.

Pre-Clinical Studies

In pre-clinical studies, HuMax-CD38 was effective in killing primary multiple myeloma tumor cells and a range of tumor cell lines by triggering two immune system killing mechanisms:  Antibody-Dependent Cellular Cytotoxicity (ADCC) and Complement Dependent Cytotoxicity (CDC).  HuMax-CD38 was more effective in triggering these mechanisms than a broad array of other human CD38 antibodies when tested on a panel of over 10 primary tumors from multiple myeloma patients.  HuMax-CD38 also potently killed tumor cells from a patient with a CD38/138 positive plasma cell leukemia which was refractory to chemotherapy at the time of analysis.  Plasma cell leukemia is a manifestation of multiple myeloma in which tumor cells are present in the blood.  Click here to view a poster of these pre-clinical results. 

HuMax-CD38 was also shown to inhibit the enzymatic activity of the CD38 molecule in preclinical studies. HuMax-CD38 is the first antibody known to block the ecto-enzymatic activity of CD38. This special property may contribute to the effectiveness of HuMax-CD38 in killing both primary multiple myeloma and plasma cell leukemia cells.

In animal models using sensitive bioluminescence imaging, treatment with HuMax-CD38 slowed tumor growth in a therapeutic setting and also effectively prevented the growth of CD38 positive cancer cells in SCID mice.  These are mice with deficient immune systems in which human tumor cells can grow.