Genmab A/S said it has initiated a phase I/II safety and dose finding study of HuMax-CD38 for the treatment of multiple myeloma (MM). 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.

"HuMax-CD38 is the ninth Genmab antibody to enter clinical development," said Lisa N. Drakeman, Ph.D., chief executive officer, Genmab. "We are looking forward to the results of this safety study and hope that HuMax-CD38 may one day offer a new potential treatment for multiple myeloma patients who have run out of treatment options."

This open label dose escalation safety 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 safety and efficacy and will be followed every 12 weeks thereafter until disease progression, initiation of alternative treatment for MM or death for a maximum total of 2 years from study start.

HuMax-CD38 is a fully human antibody that targets the CD38 molecule which is highly expressed on the surface of multiple myeloma tumour cells. In preclinical studies, HuMax-CD38 was more effective in triggering the immune system killing mechanisms Antibody-Dependent Cellular Cytotoxicity (ADCC) and Complement Dependent Cytotoxicity (CDC), than other human CD38 antibodies when tested on multiple myeloma tumours. HuMax-CD38 also potently killed tumour cells from a patient with a CD38/138 positive plasma cell leukaemia which was refractory to chemotherapy at the time of analysis. Furthermore, treatment with HuMax-CD38 slowed tumour growth in both preventive and therapeutic settings in SCID mice in animal models. HuMax-CD38 is the first antibody known to block the ecto-enzymatic activity of CD38.

Multiple Myeloma is a plasma cell disorder, characterized by uncontrolled and progressive proliferation of a plasma cell clone. The proliferation of myeloma cells causes displacement of the normal bone marrow. MM accounts for approximately 1 per cent of all malignancies and 10% of all hematologic malignancies with a higher frequency in African Americans where MM accounts for 20 per cent of all hematologic malignancies. In the US, approximately 11,000 deaths each year are related to MM and the estimated number of new cases is rising. At present, no cure is available, and the mean survival is approximately 3-5 years.