On December 10, 2017 Seattle Genetics, Inc. (Nasdaq: SGEN) reported final five-year survival results from a phase 1 clinical trial evaluating ADCETRIS (brentuximab vedotin) in mature T-cell lymphoma (MTCL) at the 59th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition taking place in Atlanta, Georgia, December 9-12, 2017 (Press release, Seattle Genetics, DEC 10, 2017, View Source;p=RssLanding&cat=news&id=2321959 [SID1234522496]). The presentation highlighted durability data from a phase 1 clinical trial of ADCETRIS in combination with chemotherapy for the treatment of patients with newly diagnosed MTCL, also known as peripheral T-cell lymphoma (PTCL). 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. ADCETRIS is currently not approved for the frontline treatment of MTCL.

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"Approximately 4,000 patients are diagnosed with MTCL each year. The current standard of care for frontline MTCL treatment has not changed for several decades and there remains a significant need for improved therapeutic options. The results of this phase 1 trial support the ongoing phase 3 ECHELON-2 clinical trial and our goal to redefine frontline MTCL treatment with a novel ADCETRIS combination regimen," said Jonathan Drachman, M.D., Chief Medical Officer and Executive Vice President, Research and Development at Seattle Genetics. "The final results from the phase 1 study were presented today, with five-year progression-free survival and overall survival rates of 52 and 80 percent, respectively. No patients have experienced any disease progression events since the three-year follow-up results. Importantly, after more than five years of follow-up, patients who remain in remission have the potential to be cured. These data continue to support the phase 3 ECHELON-2 trial, from which we anticipate reporting data in 2018."

Five-Year Survival Results: Frontline Brentuximab Vedotin in Combination with CHP in Patients with CD30-Expressing Peripheral T-Cell Lymphomas (Abstract #2790, poster presentation on Sunday, December 10, 2017)

Data were reported from 26 frontline MTCL patients who received the combination regimen of ADCETRIS plus cyclophosphamide, doxorubicin and prednisone (CHP). Patients who achieved at least a partial remission with combination therapy following six cycles of ADCETRIS plus CHP were eligible to receive up to ten additional cycles of single-agent ADCETRIS treatment. The median age of patients was 56 years. Nineteen patients (73 percent) had a subtype of MTCL called systemic anaplastic large cell lymphoma (sALCL), including 16 patients with anaplastic lymphoma kinase (ALK)-negative disease, which is typically associated with a poor prognosis. Seven patients (27 percent) had a diagnosis of other types of MTCL. The majority of patients had advanced stage disease and were considered high risk. All patients on the trial achieved an objective response, including 92 percent with a complete response and eight percent with a partial response.

Updated key findings based on a median observation time of 60 months from first dose of therapy include:

At five-year follow-up, there have been no progression events or deaths in this trial since the three-year follow up.
The estimated five-year progression-free survival rate was 52 percent, with no patients receiving a consolidative stem cell transplant in first remission. The median progression-free survival has not yet been reached.
The estimated five-year overall survival rate was 80 percent. The median overall survival has not yet been reached.
Seventy-three percent of patients (19 of 26) experienced peripheral neuropathy, the majority of which was Grade 1 or 2. Ninety-five percent of these patients had complete resolution or some improvement of their symptoms at last follow-up with a median time to resolution of 4.2 months and median time to improvement of symptoms was 2.6 months.
A global phase 3 study called ECHELON-2 completed enrollment in November 2016. The ECHELON-2 trial is a randomized, double-blind, placebo-controlled, multi-center trial designed to investigate ADCETRIS plus CHP versus CHOP as frontline therapy in patients with CD30-expressing MTCL. The trial enrolled 452 patients (approximately 225 patients per treatment arm) randomized to receive ADCETRIS plus CHP or CHOP every three weeks for six to eight cycles. Data from the ECHELON-2 trial are expected in 2018.

About T-Cell Lymphomas

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. Non-Hodgkin lymphomas are broadly divided into two major groups: B-cell lymphomas, which develop from abnormal B-lymphocytes, and T-cell lymphomas, which develop from abnormal T-lymphocytes. T-cell lymphomas account for approximately 15 percent of all non-Hodgkin lymphoma in the United States. There are many different forms of T-cell lymphomas, some of which are extremely rare. T-cell lymphomas can be aggressive (fast-growing) or indolent (slow-growing). Almost all types of T-cell lymphoma fall under the category of mature T-cell lymphoma, also known as peripheral T-cell lymphoma. According to the American Cancer Society and analysis of literature sources, approximately 4,300 patients will be diagnosed with CD30-expressing mature T-cell lymphoma in the United States during 2017.

About ADCETRIS

ADCETRIS is being evaluated broadly in more than 70 clinical trials, including three phase 3 studies: the completed ECHELON-1 trial in frontline classical Hodgkin lymphoma that supported the recent FDA Breakthrough Therapy Designation and submission of the supplemental Biologics License Application (BLA) for use in this setting, the ongoing ECHELON-2 trial in frontline mature T-cell lymphomas, and the ongoing 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-expressing tumor cells.

ADCETRIS injection for intravenous infusion has received FDA approval for four indications: (1) regular approval for adult patients with primary cutaneous anaplastic large cell lymphoma (pcALCL) or CD30-expressing mycosis fungoides (MF) who have received prior systemic therapy, (2) 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, (3) regular approval for the treatment of classical Hodgkin lymphoma patients at high risk of relapse or progression as post-auto-HSCT consolidation, and (4) 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 69 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.