|Seattle Genetics Reports Data from Phase I Trial of ADCETRIS® (Brentuximab Vedotin) in Front-line Hodgkin Lymphoma at ASH Annual Meeting|
- 96 Percent Complete Remission Rate in Newly Diagnosed Hodgkin Lymphoma Patients Treated with ADCETRIS in Combination with AVD Chemotherapy -
- Safety and Response Data Support Ongoing Phase III Trial of ADCETRIS and AVD Chemotherapy in Patients with Newly Diagnosed Hodgkin Lymphoma -
In the phase I trial, newly diagnosed patients received ADCETRIS concomitantly with either ABVD (Adriamycin, bleomycin, vinblastine and dacarbazine) or AVD, which removes bleomycin from the regimen. At the end of front-line therapy, 24 of 25 patients (96 percent) treated with ADCETRIS plus AVD and 21 of 22 (95 percent) patients treated with ADCETRIS plus ABVD had a complete remission. None of the patients treated in the ADCETRIS plus AVD cohort experienced pulmonary toxicity, compared with an expected rate of pulmonary toxicity caused by ABVD alone of 10-25 percent. The trial was designed to establish the safety profile and maximum tolerated dose when adding ADCETRIS to ABVD or AVD. Antitumor activity was assessed as a secondary endpoint.
"For over 30 years, the standard of care for front-line HL has been a
chemotherapy regimen called ABVD that has demonstrated a complete
remission rate of 70 to 80 percent and is associated with considerable
life-threatening toxicities. There is a significant need to identify
better treatment options for patients in the front-line HL setting,”
Front-line Therapy with Brentuximab Vedotin Combined with ABVD or AVD in Patients with Newly Diagnosed Advanced Stage Hodgkin Lymphoma (Abstract #798)
In this open-label, multicenter trial, cohorts of patients received an escalating dose of ADCETRIS (0.6 milligrams per kilogram (mg/kg), 0.9 mg/kg, 1.2 mg/kg) every two weeks concomitantly with ABVD or a dose of 1.2 mg/kg every two weeks concomitantly with AVD.
Fifty-one patients were enrolled in the phase I study and 47 were
evaluable for response at trial completion. The 47 evaluable patients
included 25 in the ADCETRIS plus AVD cohort and 22 in the ADCETRIS plus
ABVD cohorts. All patients were previously untreated and 45 percent had
Stage IV HL. The median age of patients across all cohorts of the trial
was 33 years. Key findings, which were highlighted in an oral
presentation by Dr.
“For decades researchers have strived to improve our front-line HL
treatment strategy by enhancing the activity of traditional chemotherapy
regimens while reducing the significant toxicities and long-term side
effects of such regimens,” said Stephen Ansell, M.D., Ph.D., Professor
ADCETRIS (brentuximab vedotin) is an ADC comprising an anti-CD30 monoclonal antibody attached by a protease-cleavable linker to a microtubule disrupting agent, monomethyl auristatin E (MMAE), utilizing Seattle Genetics’ proprietary technology. The ADC employs a linker system that is designed to be stable in the bloodstream but to release MMAE upon internalization into CD30-expressing tumor cells.
ADCETRIS received accelerated approval from the
ADCETRIS was granted conditional marketing authorization by the
About Hodgkin Lymphoma
Lymphoma is a general term for a group of cancers that originate in the lymphatic system. There are two major categories of lymphoma: Hodgkin lymphoma and non-Hodgkin lymphoma. Hodgkin lymphoma is distinguished from other types of lymphoma by the presence of one characteristic type of cell, known as the Reed-Sternberg cell. The Reed-Sternberg cell generally expresses CD30.
U.S. Important Safety Information
Progressive multifocal leukoencephalopathy (PML): JC virus infection resulting in PML and death can occur in patients receiving ADCETRIS.
Concomitant use of ADCETRIS and bleomycin is contraindicated due to pulmonary toxicity.
Warnings and Precautions:
ADCETRIS was studied as monotherapy in 160 patients in two phase 2 trials. Across both trials, the most common adverse reactions (≥20%), regardless of causality, were neutropenia, peripheral sensory neuropathy, fatigue, nausea, anemia, upper respiratory tract infection, diarrhea, pyrexia, rash, thrombocytopenia, cough and vomiting.
Patients who are receiving strong CYP3A4 inhibitors concomitantly with ADCETRIS should be closely monitored for adverse reactions.
Certain of the statements made in this press release are forward
looking, such as those, among others, relating to the therapeutic
potential of ADCETRIS in the featured indication and initiation of
future clinical trials. Actual results or developments may differ
materially from those projected or implied in these forward-looking
statements. Factors that may cause such a difference include the
inability to show sufficient activity in the phase III trial and the
risk of adverse events as ADCETRIS advances in clinical trials. In
addition, data from our clinical trials, including our pivotal trials
which were the basis for