Relapsed/Refractory Patients

Siltuximab (CNTO 328)

What is Siltuximab (CNTO 328)?

Siltuximab, also known as CNTO 328, is a monoclonal antibody being developed by Janssen Biotech, Inc. that neutralizes interleukin-6 (IL-6), a growth factor for myeloma cells. Siltuximab is given as an intravenous infusion.

What do we know about Siltuximab’s activity in myeloma?

Siltuximab has demonstrated anti-myeloma activity in the laboratory and in animal models, and the effect is synergistic with agents such as dexamethasone, melphalan, and Velcade® (bortezomib). Siltuximab was also able to re-sensitize cells that were previously resistant to melphalan.

Results of a small safety analysis (n=21) done as a run-in to a larger ongoing Phase II trial showed promising preliminary efficacy of siltuximab in combination with Velcade in relapsed/refractory myeloma.

• The overall response rate was 57% and the median time until the disease progressed was 8.7 months.

The combination of siltuximab and dexamethasone showed promising activity in a Phase II study in patients with relapsed or refractory myeloma (n=44) who had previously received Velcade, with 20% of patients achieving a partial response.

How is Siltuximab currently being studied in myeloma?

Siltuximab in combination with Velcade and dexamethasone is being evaluated in a Phase III trial, where it will be compared with Velcade and dexamethasone.

• The trial, which is set to begin, will enroll 500 patients who have received 1 to 3 prior lines of treatment for their disease.
  
  
• The study will evaluate the length of time patients’ disease does not get worse (progression-free survival), as well as overall survival, response rates, and safety.

Siltuximab is also being evaluated as part of combination therapy for initial treatment of myeloma in a Phase II trial. The safety and effectiveness of siltuximab plus Velcade-melphalan-prednisone (VMP) will be compared with VMP.

The cardiac safety of siltuximab in patients with monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma, or indolent multiple myeloma is being assessed in a Phase I study being facilitated by the MMRC.

To find a clinical trial, call 1-866-603-MMCT (-6628) or click here to go to the MMRF Patient Navigator Program.