Seattle Genetics and partner Takeda Pharmaceutical Co have presented two lots of promising data for brentuximab vedotin, the firms’ novel antibody-drug conjugate, in Hodgkin’s lymphoma and anaplastic large cell lymphoma.
First up, data was presented at the American Society of Hematology meeting in Orlando on the treatment, also known as SGN-35, which demonstrated encouraging activity in heavily pre-treated patients with relapsed or refractory Hodgkin lymphoma (HL), with three-quarters of them achieving an objective response. In the Phase II study, 102 patients who had previously undergone autologous stem cell transplantation received brentuximab 1.8 mg/kg every three weeks as a 30 minute outpatient intravenous infusion for up to 16 treatment cycles.
The results showed that 75% of patients achieved an objective response and 34% achieved a complete remission. 40% achieved a partial response, while 96 out of 102 achieved tumour reduction. The most common adverse events of any grade were peripheral sensory neuropathy (47%), fatigue (46%), nausea (42%), upper respiratory tract infection (37%) and diarrhoea (36%).
Brentuximab is an ADC targeted to CD30, a defining marker of HL. Once internalised the drug, monomethyl auristatin E, binds to tubulin, thereby inducing cell cycle arrest.
While around 70% of patients with newly-diagnosed HL are cured with combination therapy, 30% will go on to experience relapse. “These patients have limited treatment options beyond autologous stem cell transplantation and represent a significant unmet medical need,” explained study presenter Robert Chen, from the City of Hope National Medical Center in Duarte, California, adding that without additional treatment such patients had a median survival of 2.4 years.
Brentuximab “is very active for a single agent, particularly bearing in mind that patients in this study had failed a median number of 3.5 prior regimens”, said Dr Chen, adding that response rates are typically highest when given upfront and usually drop in the second and third line setting. He added that based on these data, brentuximab “has the potential to change the treatment paradigm for relapsed or refractory HL patients, and could be the first treatment approved for these patients in more than 20 years”.
The company hopes to submit the medication to the US Food and Drug Administration for approval during the first quarter of 2011, earlier than previously forecast, and to European regulators during the first half of next year.
Filings for brentuximab are also planned at the same time for relapsed or refractory systemic anaplastic large cell lymphoma (ALCL). In a second Phase II study presented at ASH involving 58 patients, 86% achieved an objective response and 53% achieved a complete remission. Tumour reductions were achieved in 97% of patients.