Seattle Genetics reports data encouraging on lymphoma-targeting monoclonal antibody

07-03-2006

Seattle Genetics, Inc. (SGEN) reported encouraging data from its phase 1 clinical trial of SGN-40 in non-Hodgkin lymphoma at the American Society of Clinical Oncology (ASCO) 42nd Annual Meeting in Atlanta, Georgia.

SGN-40 induced objective responses in five patients and was well tolerated at doses up to 8 milligrams per kilogram. The company is completing treatment of the final cohort of patients and plans to advance SGN-40 into phase 2 clinical trials.

Non-Hodgkin lymphoma (NHL) represents a diverse group of cancers that develop in the lymphatic system. When lymphocytes, or white blood cells, which are responsible for defending the body against infection, divide and multiply uncontrollably, malignant tumors can form. An estimated 360,000 Americans have NHL.

SGN-40 is a humanized monoclonal antibody that targets the CD40 antigen, which is expressed on most B-cell lineage hematologic malignancies. Seattle Genetics reported data from its open-label, multi-dose, single-arm phase 1 clinical trial of SGN-40 in patients with relapsed or refractory non-Hodgkin lymphoma. The study is designed to evaluate the safety, antitumor activity, pharmacokinetic profile and immunogenicity of escalating doses of SGN-40. Patients who experience a clinical benefit are eligible for a second cycle of therapy.

Data were reported on 29 non-Hodgkin lymphoma patients with a median age of 59 years and a median of 3.5 prior therapies. One cohort of patients received weekly doses of SGN-40 over 4 weeks and subsequent cohorts received SGN-40 using an intra-patient dose-loading schedule over 5 weeks. SGN-40 was well tolerated up to 8 mg/kg/week with adverse events generally occurring during the dose-loading segment of therapy rather than at the maximum dose evaluated. No immune responses to SGN-40 have been detected among the 16 patients evaluated thus far.

Five patients achieved an objective antitumor response. Four patients had partial responses, including two at 3 mg/kg, one at 6 mg/kg and one at 8 mg/kg. One patient in the 4 mg/kg cohort had a complete response following one cycle of SGN-40 treatment that is ongoing after 20 weeks. Four of the five objective responses were in patients with aggressive subtypes of non-Hodgkin lymphoma, including three with diffuse large B-cell lymphoma and one with mantle cell lymphoma. In addition, three patients had stable disease, seventeen had progressive disease and four were not evaluable for clinical response.

The final cohort of patients is currently being treated using an accelerated dose-loading schedule.

SGN-70 is a humanized monoclonal antibody that targets the CD70 antigen, which is expressed on a variety of hematologic malignancies, as well as several solid tumor types such as renal cancer. In preclinical research, CD70 was shown to be widely expressed on Waldenstrom's macroglobulemia (WM) patient samples, suggesting that blocking CD70 may result in a therapeutic effect in preventing WM disease progression. In these studies, SGN-70 also demonstrated significant antibody-dependent cellular cytotoxicity (ADCC) activity. Seattle Genetics plans to file an investigational new drug (IND) application for SGN-70 in 2007 (Abstract #2509: Therapeutic targeting of CD70 and CD27-CD70 interactions with the monoclonal antibody SGN-70 in Waldenstrom's macroglobulinemia).

SGN-33, a humanized monoclonal antibody that targets CD33, is in an ongoing dose-escalation phase 1 clinical trial for patients with myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML). Seattle Genetics reported data from the first cohort of six patients treated with SGN-33 at a dose of 1.5 mg/kg/week. SGN-33 was well tolerated and demonstrated signs of antitumor activity, including decreases in bone marrow blasts and marrow monocytes. Dose escalation is ongoing with additional data planned to be reported at ASH (Abstract #16500: A humanized unconjugated antibody targeting CD33 (SGN-33; huM195)) is active in patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), was published as an abstract only.

This article was prepared by Biotech Business Week editors from staff and other reports. Copyright 2006, Biotech Business Week via NewsRx.com.