Post by Deanne Jenkyns on Aug 20, 2007 20:47:38 GMT 1
Small Cell Lung Cancer antibody drug shows promise in phase I trial
A novel immunoconjugate that delivers a cytotoxic agent to small-cell lung cancer (SCLC) cells has achieved promising tolerability in an ongoing phase I trial, UK and US researchers report.
The targeted therapy, BB-10901, is created by attaching the cytotoxic drug DM1 to a monoclonal antibody, huN901. This antibody binds to CD56 adhesion molecules, which are found on SCLC cells. Once binding occurs, BB-10901 is internalized and releases DM1.
Other tumors that express CD56 include neuroendocrine tumors, Wilms' tumors, and multiple myeloma.
The investigators, led by Paul Lorigan from Christie Hospital in Manchester, UK, have trialled BB-10901 on patients with relapsed or refractory SCLC, other pulmonary tumors of neuroendocrine origin, non-pulmonary small cell carcinoma, and metastatic carcinoid tumors.
Ten groups of four patients received doses of BB-10901 of 4, 8, 16, 24, 36, 48, 60, or 75 mg/m2 per day, for 3 consecutive days every 3 weeks.
One patient with relapsed, metastatic CD56-positive Merkel cell carcinoma responded completely for at least 15 weeks, and remains in clinical remission after more than 1 year off therapy.
Eight subjects experienced disease stabilization for a median of around 10 weeks, according to RECIST criteria.
Constipation, fatigue, elevated amylase/pancreatitis, hypotension and myocardial infarction, leg pain, and severe headache were all experienced by at least one patient.
One further patient experienced severe headache that proved dose-limiting, though Lorigan commented that this adverse event "seems to be reduced if we increase the infusion time, and it may respond to other medication given with the study drug."
He added at the Symposium on Molecular Targets and Cancer in Prague, Czech Republic: "A durable, complete response as well as other hints of clinical activity are very encouraging."
A novel immunoconjugate that delivers a cytotoxic agent to small-cell lung cancer (SCLC) cells has achieved promising tolerability in an ongoing phase I trial, UK and US researchers report.
The targeted therapy, BB-10901, is created by attaching the cytotoxic drug DM1 to a monoclonal antibody, huN901. This antibody binds to CD56 adhesion molecules, which are found on SCLC cells. Once binding occurs, BB-10901 is internalized and releases DM1.
Other tumors that express CD56 include neuroendocrine tumors, Wilms' tumors, and multiple myeloma.
The investigators, led by Paul Lorigan from Christie Hospital in Manchester, UK, have trialled BB-10901 on patients with relapsed or refractory SCLC, other pulmonary tumors of neuroendocrine origin, non-pulmonary small cell carcinoma, and metastatic carcinoid tumors.
Ten groups of four patients received doses of BB-10901 of 4, 8, 16, 24, 36, 48, 60, or 75 mg/m2 per day, for 3 consecutive days every 3 weeks.
One patient with relapsed, metastatic CD56-positive Merkel cell carcinoma responded completely for at least 15 weeks, and remains in clinical remission after more than 1 year off therapy.
Eight subjects experienced disease stabilization for a median of around 10 weeks, according to RECIST criteria.
Constipation, fatigue, elevated amylase/pancreatitis, hypotension and myocardial infarction, leg pain, and severe headache were all experienced by at least one patient.
One further patient experienced severe headache that proved dose-limiting, though Lorigan commented that this adverse event "seems to be reduced if we increase the infusion time, and it may respond to other medication given with the study drug."
He added at the Symposium on Molecular Targets and Cancer in Prague, Czech Republic: "A durable, complete response as well as other hints of clinical activity are very encouraging."
LC charity Ball