The study, entitled: "Phase I Trial of Siplizumab in CD2-Positive Lymphoproliferative Disease," was to determine the maximum tolerated dose, safety and tolerability of siplizumab in patients with CD2-positive lymphoproliferative disorders, including CD2-postive peripheral T-cell lymphoma, adult T-cell leukaemia/lymphoma, cutaneous T-cell lymphoma and large granular lymphocytic leukaemia.
Partial disease remissions for some study participants were among the data presented by the National Cancer Institute (NCI) during a poster session at the 41st American Society of Clinical Oncology (ASCO) Annual Meeting in Orlando, Florida.
Siplizumab is a humanised monoclonal antibody that binds to the CD2 receptor found on the surface of T-cells and natural killer (NK) cells. In both preclinical and clinical studies, siplizumab has been shown to cause depletion of T-cells.
Siplizumab is therefore considered to be an immunomodulator in clinical settings where the depletion of T-cells may have clinical benefits, such as certain autoimmune diseases and T-cell cancers. In addition, preclinical studies have also demonstrated that siplizumab, by binding to the CD2 receptor, may selectively produce cell death and reduce cancerous cells.
MedImmune has previously conducted clinical development programs with siplizumab in patients with other conditions, including psoriasis, graft- versus-host disease and renal transplantation
The trial included cohorts of three patients each who receive escalating doses of siplizumab intravenously every other week for 16 weeks or until unacceptable toxicity or disease progression. The ASCO presentation includes data from 13 patients enrolled into the first four cohorts of the study.
"We are encouraged by the data collected, and to find the maximum tolerated dose, particularly since three of the patients participating in the NCI trial have achieved partial disease remissions," said Dirk Reitsma, vice president, clinical development of oncology at MedImmune.
Reitsma added that from initial observations of this Phase 1 trial, MedImmune would enrol patients in an additional Phase 1/2 study using similar dose escalation criteria.
"Once the maximum tolerated dose of siplizumab is defined in the study, we will expand the number of patients treated at that dose level in our Phase 1/2 trial to evaluate the antibody's safety profile and to further define clinical activity," he added.
Medimmune have its work cut out for them as they enter a market heavy in mabs jostling for position. Key products in this category include Roche/Genentech's Rituxan/MabThera (rituximab) and Johnson & Johnson's Remicade (infliximab).
Now, more recently launched humanised antibodies, including Roche/Genentech's Avastin (bevacizumab) and Herceptin (trastuzumab) and Bristol-Myers Squibb's Erbitux (cetuximab), are also starting to make a real commercial impact, along with the first fully human antibody, Abbott's Humira (adalimumab).
Market analysts, Datamonitor have recently commented of the significant growth achieved in this market during 2004. The mAbs market achieved global sales increasing by 48 per cent to pass the $10 billion (€7.8 billion) mark, which builds on the momentum achieved in previous years.
The report expected the antibody industry to have a promising future. Beyond fully human antibodies, conjugated antibodies (linked to small molecule drugs, toxins, or radioactive payloads) have shown strong theoretical potential, particularly in the treatment of cancers.
Cancers that develop in the lymphatic system of the body is generally termed a lymphoma while leukaemia is a cancer of the bone marrow and blood. T- cell lymphomas are a subset of non-Hodgkin's lymphomas and tend to express the CD2 antigen, which may provide a target for monoclonal antibodies.
The Leukaemia & Lymphoma Society estimated that about 62,250 Americans would be diagnosed with lymphoma in 2004. This figure includes approximately 54,370 new cases of non-Hodgkin's lymphoma, of which approximately seven to 10 percent can be characterized as T-cell lymphomas. An estimated 33,440 new cases of leukaemia will be diagnosed in the United States this year with acute lymphocytic leukaemia accounting for slightly more than 10 per cent of these cases.