A Phase 1 Study of the Safety, Tolerability, Pharmacokinetics and Radiologic Distribution of Ascending Single-Dose Radiolabeled MORAb-028 in Subjects With Metastatic Melanoma
Melanoma is a serious form of skin cancer. If untreated, the melanoma can spread beyond the
original affected tissue and invade distant tissue and organs. Treatment for metastatic
melanoma includes medical treatments (chemotherapy or immunotherapy), surgery, or radiation
therapy. MORAb-028 is a recombinant human immunoglobulin M (IgM) monoclonal antibody that
recognizes a cell surface diacyl ganglioside named disialoganglioside (GD2). GD2 is
overexpressed in tumors of neuro-ectodermal origin such as melanomas, neuroblastomas,
small-cell lung carcinomas, and many sarcomas, while absent in most normal tissues. GD2
expression has been demonstrated in human melanoma and small cell lung cancer by thin layer
chromatography and radiolabeled anti-GD2 antibody detection. It is hypothesized that one
mode of action of MORAb-028 is complement-dependent cytotoxicity. Complement-dependent
cytotoxicity is a mechanism for killing tumor cells in which an antibody bound to the target
cell surface fixes complement, which results in assembly of the complement membrane attack
complex that punches holes in the target cell membrane resulting in subsequent cell lysis.
IgMs strongly bind to C1Q and robustly activate complement-dependent cytotoxicity.
MORAb-028 is being developed as a potential therapy for GD2-positive tumors.
Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Safety of single dose radio labeled MORAb-028 in subjects with metastatic melanoma
Daily for 7 days followed by weekly for 2 weeks, then biweekly for 4 weeks
Christina Coughlin, MD, PhD
United States: Food and Drug Administration
|Memorial Sloan-Kettering Cancer Center||New York, New York 10021|