Trial Watch: Antibody–Drug Conjugate Shows Efficacy in Lymphoma

News & aNalysis

BioBusiness Briefs

Trial WaTch

Antibody–drug conjugate shows meeting; abstract 283) showed that 75% of patients achieved an objective response, efficacy in lymphoma 94% of patients had a reduction in tumour size and 34% of patients showed complete remission. The median duration of response Data from two Phase II clinical trials of the primary end point of the trial; the median was 29 weeks by independent review and brentuximab vedotin — a monoclonal duration of response is yet to be determined), 47 weeks by investigator-led assessment; antibody targeting CD30 linked to the anti- with 53% of patients demonstrating complete the median duration of response in patients microtubule agent monomethyl auristatin E remission. Moreover, reductions in tumour showing complete remission is still under — highlighted the positive effects of the burden were observed in 97% of patients. investigation. The developers of brentuximab antibody–drug conjugate in anaplastic large An advantage of brentuximab vedotin vedotin (Seattle Genetics and Millennium cell lymphoma (ALCL) and in Hodgkin’s is that it can be delivered in a relatively Pharmaceuticals) plan to file for regulatory lymphoma, These are two indications in which selective way to malignant cells. “CD30 is approval of the drug for ALCL and Hodgkin’s no new drugs have been approved for decades. highly expressed on malignant cells in ALCL lymphoma, in the United States and Europe, The development of brentuximab vedotin and in Hodgkin’s lymphoma, but very few within the first half of this year. is a very important step forward, according other cells express CD30 — its expression Will brentuximab vedotin be beneficial in to Anas Younes, director of the clinical and is limited to activated T cells and virally other cancers? “Although cancers — such as translational research programme at the infected cells,” says Stephen Ansell, from embryonal cancer and T cell lymphoma — University of Texas MD Anderson Cancer the Department of Hematology at the Mayo can express CD30, its expression is low and Center in Houston, USA, who was involved Clinic, Minnesota, USA, who was a senior rare, making the potential use of this drug in the Hodgkin’s lymphoma trial: “There author in the Hodgkin’s lymphoma trial. somewhat specific for ALCL and Hodgkin’s is an urgent need to improve the treatment “CD30 is internalized when the ligand binds lymphoma,” according to Ansell. “However, it outcome of patients with ALCL whose to it, making CD30 a perfect way to deliver is noteworthy that antibody–drug conjugates tumours do not express the anaplastic drugs into the malignant c e l l .” are being explored further, using different lymphoma kinase protein. These patients have As Younes highlights: “There is also a targets to deliver similar antimicrotubule a low cure rate with standard chemotherapy need to improve the cure rate for patients drugs. For example, SGN-75 targets regimens, so novel agents such as brentuximab with advanced stage and relapsed Hodgkin’s monomethyl auristatin F to CD70, which is vedotin have the potential to improve their lymphoma, as the standard regimen currently more widely expressed.” SGN-75 is in clinical cure rate. Moreover, there is an urgent need to used offers a low cure rate in this patient trials for the treatment of non-Hodgkin’s develop new treatment strategies for patients population. For patients with Hodgkin’s lymphoma and renal cell carcinoma. In with relapsed ALCL,” Younes adds. lymphoma, a relapse after a stem cell transplant addition, trastuzumab–DM1, which is a Interim data from 30 patients enrolled in represents an unmet medical need, as the monoclonal antibody targeting ERBB2 (also the ALCL trial — presented at the American expected median survival is less than 3 years.” known as HER2) conjugated to a maytansine Society of Hematology 2010 meeting (abstract Preliminary data from the trial of derivative, is currently in clinical trials for the 961) — showed that 86% of individuals 102 patients with relapsed or refractory treatment of HER2-positive breast cancer (see achieved an objective response (which was Hodgkin’s lymphoma (presented at the same Nature Rev. Drug Discov. 9, 665–667; 2010).