Seattle Genetics Announces ADCETRIS(R) Clinical Data to be Reported in Multiple Presentations at ASCO Annual Meeting
-70 percent objective response rate in retreatment trial-
CHICAGO, Jun 02, 2012 (BUSINESS WIRE) -- ---Multiple objective responses observed in CD30-positive non-Hodgkin lymphoma patients, including four of seven patients with diffuse large B-cell lymphoma-
---First report of CD30 expression from comprehensive screening in broad range of non-lymphoma malignancies-
Seattle Genetics, Inc. SGEN today announced that data from several clinical trials of ADCETRIS (brentuximab vedotin) will be presented at the 2012 American Society of Clinical Oncology (ASCO) Annual Meeting being held June 1-5, 2012 in Chicago, IL. Data demonstrate the activity and tolerability when patients are retreated with ADCETRIS, the activity and tolerability of ADCETRIS in CD30-positive non-Hodgkin lymphomas and CD30 expression from a screening protocol in non-lymphoma malignancies. ADCETRIS is an antibody-drug conjugate (ADC) directed to CD30.
"Our goal is for ADCETRIS to become the foundation of therapy for CD30-positive malignancies and, to that end, we are aggressively investing in its clinical development and broadly exploring CD30 expression across numerous cancer types," said Clay B. Siegall, Ph.D., President and Chief Executive Officer of Seattle Genetics. "Our data presentations at ASCO highlight the potential for ADCETRIS and reinforce our development strategy to generate data that will support stepwise growth of ADCETRIS for patients with CD30-expressing malignancies."
Retreatment with brentuximab vedotin in CD30-positive hematologic malignancies: a phase II study (Abstract #8027)
In a phase II trial, patients who previously responded to treatment with ADCETRIS, then discontinued treatment and subsequently had disease progression or relapse were eligible for retreatment. Data were reported from 24 patients treated to date on the study, including 16 with Hodgkin lymphoma (HL) and eight with systemic anaplastic large cell lymphoma (sALCL). Patients had received a median of four prior systemic therapies, including ADCETRIS. Key findings include:
-- Of 23 evaluable patients, 70 percent (16 of 23) achieved an objective response after retreatment with ADCETRIS, including nine complete remissions (CRs) and seven partial remissions (PRs).
-- Median duration of retreatment objective response was 8.8 months.
-- Among retreated HL patients, nine of 16 (56 percent) achieved an objective response. Among retreated sALCL patients, seven of eight (88 percent) achieved an objective response.
-- The most common adverse events were peripheral neuropathy (46 percent), nausea (42 percent), fatigue (38 percent), diarrhea (33 percent) and fever (29 percent).
-- The phase II retreatment trial is ongoing.
Details of the poster discussion presentation are as follows:
-- Saturday, June 2; 8:00 a.m. to 1:00 p.m. Central Time (CT), with discussion from 12:00 p.m. to 1:00 p.m. CT
-- Poster display in room E450b and discussion in room E354a
-- First author: Dr. Nancy L. Bartlett, Washington University, Siteman Cancer Center, St. Louis, MO
Brentuximab vedotin for relapsed or refractory non-Hodgkin lymphoma: preliminary results from a phase II study (Abstract #8070)
In a phase II clinical trial, patients with relapsed or refractory CD30-positive non-Hodgkin lymphomas, including diffuse large B-cell lymphoma (DLBCL), peripheral T-cell lymphoma and other less common lymphoma subtypes were enrolled. The trial was designed to assess the antitumor activity, duration of response and safety profile of ADCETRIS in these patients. At the time of data analysis, 28 patients had been enrolled, including 18 with B-cell malignancies and ten with T-cell malignancies. Across all patients, the median number of prior systemic therapies was three. Key findings include:
-- Of 14 patients evaluable for response, five patients (36 percent) achieved an objective response, including three CRs and two PRs.
-- Four of seven DLBCL patients treated with ADCETRIS achieved an objective response, including two CRs and two PRs.
-- Seventy-one percent of patients achieved tumor reduction.
-- ADCETRIS treatment was generally well-tolerated, with the most common adverse events being fatigue (21 percent), abdominal pain (17 percent), nausea (17 percent), chills (13 percent), diarrhea (13 percent) and vomiting (13 percent).
-- Enrollment is ongoing.
Details of the poster presentation are as follows:
-- Monday, June 4; 1:15 p.m. to 5:15 p.m. CT
-- Poster presentation in S Hall A2; poster board #35C
-- First author: Dr. Ranjana Advani, Stanford University Medical Center, Stanford, CA
ADCETRIS is not approved for the treatment of the non-Hodgkin lymphoma subtypes described in this presentation.
CD30 expression in non-lymphomatous malignancies (Abstract #3069)
In a screening study, assessment of CD30 expression was performed in patients who had a non-lymphoma malignancy and were relapsed or refractory to previous therapy, or had no alternative curative treatment option available. Patients with CD30 expression were eligible for a companion phase II clinical trial. Per the screening protocol, patients were considered to be CD30-positive and eligible for the companion clinical trial if at least 10 percent of malignant cells were positive by immunohistochemistry or at least 20 percent of malignant cells were positive by flow cytometry. At the time of data analysis, a total of 1,637 patients had been screened. Key findings include:
-- Thirty-eight patients (2 percent) and 17 different malignant diagnoses were CD30 positive per protocol.
-- The most common malignancies with CD30 expression were mesothelioma (5 of 18 patients; 28 percent), melanoma (6 of 64 patients; 9 percent), triple negative breast cancer (4 of 71 patients; 6 percent) and ovarian carcinoma (9 of 173 patients; 5 percent).
-- Assessment of CD30 expression under the screening protocol is ongoing with target enrollment of up to 3,000 patient tumor samples.
-- A phase II companion treatment protocol is ongoing to characterize the antitumor activity of ADCETRIS in patients with CD30-positive non-lymphoma malignancies and to correlate expression with activity.
Details of the poster presentation are as follows:
-- Monday, June 4; 8:00 a.m. to 12:00 p.m. CT
-- S Hall A2; poster board #16C
-- First author: Dr. Jeff P. Sharman, Willamette Valley Center Institute and Research Center, Eugene, OR
ADCETRIS is not approved for the treatment of any non-lymphoma malignancy.
For more information about the meeting, visit the ASCO annual meeting website at www.asco.org .
About ADCETRIS
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 U.S. Food and Drug Administration for two indications: (1) the treatment of patients with Hodgkin lymphoma after failure of autologous stem cell transplant (ASCT) or after failure of at least two prior multi-agent chemotherapy regimens in patients who are not ASCT candidates, and (2) the treatment of patients with systemic anaplastic large cell lymphoma (ALCL) after failure of at least one prior multi-agent chemotherapy regimen. The indications for ADCETRIS are based on response rate. There are no data available demonstrating improvement in patient-reported outcomes or survival with ADCETRIS.
ADCETRIS is not approved for use outside the United States. The marketing authorization application for ADCETRIS in relapsed or refractory Hodgkin lymphoma and sALCL, filed by Takeda Global Research & Development Centre (Europe), was accepted for review by the European Medicines Agency for review in June 2011.
Seattle Genetics and Millennium are jointly developing ADCETRIS. Under the terms of the collaboration agreement, Seattle Genetics has U.S. and Canadian commercialization rights and the Takeda Group has rights to commercialize ADCETRIS in the rest of the world. Seattle Genetics and the Takeda Group are funding joint development costs for ADCETRIS on a 50:50 basis, except in Japan where the Takeda Group will be solely responsible for development costs.
About Seattle Genetics
Seattle Genetics is a biotechnology company focused on the development and commercialization of monoclonal antibody-based therapies for the treatment of cancer. The U.S. Food and Drug Administration granted accelerated approval of ADCETRIS in August 2011 for two indications. ADCETRIS is being developed in collaboration with Millennium: The Takeda Oncology Company. In addition, Seattle Genetics has three other clinical-stage ADC programs: SGN-75, ASG-5ME and ASG-22ME. Seattle Genetics has collaborations for its ADC technology with a number of leading biotechnology and pharmaceutical companies, including Abbott, Bayer, Celldex Therapeutics, Daiichi Sankyo, Genentech, GlaxoSmithKline, Millennium, Pfizer and Progenics, as well as ADC co-development agreements with Agensys, an affiliate of Astellas, and Genmab. More information can be found at www.seattlegenetics.com .
U.S. Important Safety Information
BOXED WARNING
Progressive multifocal leukoencephalopathy (PML): JC virus infection resulting in PML and death can occur in patients receiving ADCETRIS.
Contraindication:
Concomitant use of ADCETRIS and bleomycin is contraindicated due to pulmonary toxicity.
Warnings and Precautions:
-- Peripheral neuropathy: ADCETRIS treatment causes a peripheral neuropathy that is predominantly sensory. Cases of peripheral motor neuropathy have also been reported. ADCETRIS-induced peripheral neuropathy is cumulative. Treating physicians should monitor patients for symptoms of neuropathy, such as hypoesthesia, hyperesthesia, paresthesia, discomfort, a burning sensation, neuropathic pain or weakness and institute dose modifications accordingly.
-- Infusion reactions: Infusion-related reactions, including anaphylaxis, have occurred with ADCETRIS. Monitor patients during infusion. If an infusion reaction occurs, the infusion should be interrupted and appropriate medical management instituted. If anaphylaxis occurs, the infusion should be immediately and permanently discontinued and appropriate medical management instituted.
-- Neutropenia: Monitor complete blood counts prior to each dose of ADCETRIS and consider more frequent monitoring for patients with Grade 3 or 4 neutropenia. If Grade 3 or 4 neutropenia develops, manage by dose delays, reductions or discontinuation. Prolonged (greater-than or equal to 1 week) severe neutropenia can occur with ADCETRIS.
-- Tumor lysis syndrome: Patients with rapidly proliferating tumor and high tumor burden are at risk of tumor lysis syndrome and these patients should be monitored closely and appropriate measures taken.
-- Progressive multifocal leukoencephalopathy (PML): JC virus infection resulting in PML and death has been reported in ADCETRIS-treated patients. In addition to ADCETRIS therapy, other possible contributory factors include prior therapies and underlying disease that may cause immunosuppression. Consider the diagnosis of PML in any patient presenting with new-onset signs and symptoms of central nervous system abnormalities. Evaluation of PML includes, but is not limited to, consultation with a neurologist, brain MRI, and lumbar puncture or brain biopsy. Hold ADCETRIS if PML is suspected and discontinue ADCETRIS if PML is confirmed.
-- Stevens-Johnson syndrome: Stevens-Johnson syndrome has been reported with ADCETRIS. If Stevens-Johnson syndrome occurs, discontinue ADCETRIS and administer appropriate medical therapy.
-- Use in pregnancy: Fetal harm can occur. Pregnant women should be advised of the potential hazard to the fetus.
Adverse Reactions:
ADCETRIS was studied as monotherapy in 160 patients in two phase 2 trials. Across both trials, the most common adverse reactions (greater-than or equal to 20%), regardless of causality, were neutropenia, peripheral sensory neuropathy, fatigue, nausea, anemia, upper respiratory tract infection, diarrhea, pyrexia, rash, thrombocytopenia, cough and vomiting.
Drug Interactions:
Patients who are receiving strong CYP3A4 inhibitors concomitantly with ADCETRIS should be closely monitored for adverse reactions.
For additional important safety information, including Boxed WARNING, please see the full U.S. prescribing information for ADCETRIS at www.seattlegenetics.com or www.ADCETRIS.com .
Certain of the statements made in this press release are forward looking, such as those, among others, relating to the therapeutic potential of ADCETRIS 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 future clinical trials 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 FDA accelerated approval, may not necessarily be indicative of subsequent clinical trial results. More information about the risks and uncertainties faced by Seattle Genetics is contained in the company's 10-Q for the quarter ended March 31, 2012 filed with the Securities and Exchange Commission. Seattle Genetics disclaims any intention or obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise.
SOURCE: Seattle Genetics, Inc.
Seattle Genetics, Inc.
Peggy Pinkston, 425-527-4160
[email protected]