On October 3, 2017– Seattle Genetics, Inc. (NASDAQ:SGEN) and Takeda Pharmaceutical Company Limited (TSE:4502) reported final data from the ADCETRIS (brentuximab vedotin) pivotal Phase 2 clinical trial in relapsed or refractory systemic anaplastic large cell lymphoma (sALCL) were published in the journal Blood (Press release, Seattle Genetics, OCT 3, 2017, View Source [SID1234520761]). The manuscript, which summarizes the five-year, end-of-study results, highlights durable, long-term remissions in sALCL patients treated with ADCETRIS monotherapy. The manuscript is available online today and will be included in a future print edition of Blood. ADCETRIS is an antibody-drug conjugate (ADC) directed to CD30, which is expressed on the surface of Hodgkin lymphoma cells and several types of non-Hodgkin lymphoma, including sALCL. ADCETRIS is being evaluated globally as the foundation of therapy for CD30-expressing lymphomas in more than 70 corporate- and investigator-sponsored clinical trials.
“Historically, sALCL patients who have recurrent or refractory disease have a poor prognosis and outcome with few effective and durable treatment options,” said Barbara Pro, M.D., Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, Illinois, and lead author of the Blood manuscript. “Publication of the five-year follow up from the pivotal phase 2 clinical trial results represents a significant milestone for the sALCL community by demonstrating that treatment with single-agent brentuximab vedotin resulted in high response rates and durable, long-term remissions in conjunction with a manageable safety profile.”
“These data from the pivotal trial in sALCL demonstrate the long-term clinical benefit of ADCETRIS in the treatment of this disease, with an estimated five-year survival rate of 60 percent and progression-free survival rate of 39 percent,” said Jonathan Drachman, M.D., Chief Medical Officer and Executive Vice President, Research and Development at Seattle Genetics. “In addition to achieving sustained remissions in the relapsed sALCL treatment setting, these data support the evaluation of ADCETRIS in earlier lines of therapy, including in the ongoing Phase 3 ECHELON-2 clinical trial in frontline mature T-cell lymphoma, also known as peripheral T-cell lymphoma.”
“With the five-year data of ADCETRIS in relapsed or refractory classical Hodgkin lymphoma published in Blood in July 2016, these results in sALCL represent the second CD30-expressing malignancy in which five-year data has confirmed clinically significant durable remissions,” said Jesús Gomez-Navarro, M.D., Vice President, Head of Oncology Clinical Research and Development, Takeda. “These findings further substantiate our goal to establish ADCETRIS as the foundation of therapy for CD30-expressing lymphomas.”
The pivotal, single-arm trial, which supported approvals of ADCETRIS by the FDA in 2011 and the European Medicines Agency (EMA) in 2012 for this indication, was conducted in 58 relapsed or refractory sALCL patients to assess the efficacy and safety of single-agent ADCETRIS. After a follow-up period of approximately five years, the final results from the pivotal trial include:
The median overall survival was not yet reached and median progression-free survival was estimated at 20 months (95% confidence interval [CI]: 9.4, -). The estimated five-year overall survival and progression-free survival rates were 60 percent and 39 percent, respectively.
Of the 58 patients treated, 38 patients (66 percent) had a complete remission, with the median response duration not reached. For patients who had a complete remission, the median overall survival and progression-free survival were not yet reached.
Sixteen of the 38 patients (42 percent) who achieved a complete remission continued to be followed and remained in remission for over five years at study closure. Of these patients, eight underwent either autologous or allogenic consolidative stem cell transplants while in remission, and eight received no further therapy.
The most common adverse events of any grade occurring in 20 percent or more of patients were peripheral neuropathy, nausea, fatigue, pyrexia, diarrhea, rash, constipation and neutropenia. Of the 33 patients who experienced peripheral neuropathy, 30 patients (91 percent) experienced complete resolution or some improvement of symptoms at last follow-up.
About ADCETRIS
ADCETRIS is being evaluated broadly in more than 70 clinical trials, including four Phase 3 studies: the ECHELON-1 trial in frontline classical Hodgkin lymphoma from which positive top-line results were recently reported, the ongoing ECHELON-2 trial in frontline mature T-cell lymphomas, the completed ALCANZA trial in cutaneous T-cell lymphoma that supported the supplemental BLA with a Prescription Drug User Fee Act (PDUFA) target action date of December 16, 2017, and the recently initiated CHECKMATE 812 trial of ADCETRIS in combination with Opdivo (nivolumab) for relapsed/refractory Hodgkin lymphoma.
ADCETRIS 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-positive tumor cells.
ADCETRIS for intravenous injection has received approval from the FDA for three indications: (1) regular approval for the treatment of patients with classical Hodgkin lymphoma after failure of autologous hematopoietic stem cell transplantation (auto-HSCT) or after failure of at least two prior multi-agent chemotherapy regimens in patients who are not auto-HSCT candidates, (2) regular approval for the treatment of classical Hodgkin lymphoma patients at high risk of relapse or progression as post-auto-HSCT consolidation, and (3) accelerated approval for the treatment of patients with systemic anaplastic large cell lymphoma (sALCL) after failure of at least one prior multi-agent chemotherapy regimen. The sALCL indication is approved under accelerated approval based on overall response rate. Continued approval for the sALCL indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
Health Canada granted ADCETRIS approval with conditions for relapsed or refractory Hodgkin lymphoma and sALCL in 2013, and non-conditional approval for post-ASCT consolidation treatment of Hodgkin lymphoma patients at increased risk of relapse or progression.
ADCETRIS was granted conditional marketing authorization by the European Commission in October 2012 for two indications: (1) for the treatment of adult patients with relapsed or refractory CD30-positive Hodgkin lymphoma following autologous stem cell transplant (ASCT), or following at least two prior therapies when ASCT or multi-agent chemotherapy is not a treatment option, and (2) the treatment of adult patients with relapsed or refractory sALCL. The European Commission extended the current conditional marketing authorization of ADCETRIS and approved ADCETRIS for the treatment of adult patients with CD30-positive Hodgkin lymphoma at increased risk of relapse or progression following ASCT.
ADCETRIS has received marketing authorization by regulatory authorities in 67 countries for relapsed or refractory Hodgkin lymphoma and sALCL. See important safety information below.
Seattle Genetics and Takeda are jointly developing ADCETRIS. Under the terms of the collaboration agreement, Seattle Genetics has U.S. and Canadian commercialization rights and Takeda has rights to commercialize ADCETRIS in the rest of the world. Seattle Genetics and Takeda are funding joint development costs for ADCETRIS on a 50:50 basis, except in Japan where Takeda is solely responsible for development costs.