CHICAGO--(BUSINESS WIRE)--Seattle Genetics, Inc. (Nasdaq: SGEN) today announced several ADCETRIS (brentuximab vedotin) data presentations in the AETHERA post-transplant consolidation setting for Hodgkin lymphoma (HL) and in frontline diffuse large B-cell lymphoma (DLBCL) at the American Society of Clinical Oncology (ASCO) 50th Annual Meeting being held May 29 to June 2, 2015, in Chicago, IL. ADCETRIS is an antibody-drug conjugate (ADC) directed to CD30, which is expressed in classical HL and systemic anaplastic large cell lymphoma (sALCL) and several other types of non-Hodgkin lymphoma.
“The ADCETRIS data presentations at the ASCO Annual Meeting in both Hodgkin and non-Hodgkin disease settings continue to support our vision to establish ADCETRIS as the foundation of therapy for CD30-expressing diseases,” said Clay B. Siegall, Ph.D., President and Chief Executive Officer of Seattle Genetics. “The data analyses presented from the AETHERA trial show the potential benefits to high risk HL patients of using ADCETRIS immediately following an autologous stem cell transplant to prevent progression. In non-Hodgkin lymphoma, the interim data presented in our phase 2 frontline DLBCL clinical trial evaluating ADCETRIS in combination with standard of care show encouraging activity, particularly in patients with CD30-positive disease, and we look forward to evaluating ADCETRIS further in both frontline and relapsed/refractory DLBCL.”
Multivariate analysis of PFS from the AETHERA trial: A phase 3 study of brentuximab vedotin consolidation after autologous stem cell transplant for HL (Abstract #8519, poster presentation Sunday, May 31, 2015)
Data were reported from a multivariate analysis of the effects of demographics, baseline disease characteristics and other risk factors on progression-free survival (PFS) from the phase 3 AETHERA clinical trial. After adjusting for several clinical factors in a multivariate regression analysis, consolidation treatment with ADCETRIS was significantly associated with improved PFS compared with placebo (hazard ratio of 0.44) and was more important, or as important, as all evaluated clinical factors. Results show consistent PFS benefit of ADCETRIS consolidation therapy, regardless of the clinical factors, further supporting ADCETRIS use as consolidation in HL patients following autologous stem cell transplant (ASCT).
ADCETRIS is currently not approved for use in the AETHERA treatment setting. Based on the positive results from the AETHERA trial, a supplemental Biologics License Application (BLA) for ADCETRIS in the AETHERA setting for the post-ASCT consolidation treatment of HL patients at high risk of relapse or progression was accepted for filing by the U.S. Food and Drug Administration (FDA). The FDA granted Priority Review for the application and the Prescription Drug User Fee Act (PDUFA) target action date is August 18, 2015.
Updated results of a phase 2 trial of brentuximab vedotin combined with RCHOP in frontline treatment of pts with high-intermediate/high-risk DLBCL (Abstract #8506, oral presentation Monday, June 1, 2015, at 11:21 a.m. CT)
Interim results were reported from an ongoing phase 2 clinical trial evaluating ADCETRIS in combination with the standard of care regimen consisting of rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (RCHOP) in frontline high-intermediate or high-risk DLBCL. Patients were randomized to receive standard dose RCHOP with either 1.2 milligrams per kilogram (mg/kg) (30 patients) or 1.8 mg/kg (23 patients) of ADCETRIS. The trial was designed to assess antitumor activity and the safety profile of ADCETRIS plus RCHOP in these patients.
Data were reported from 53 patients with a median age of 67 years. Nearly all (96 percent) had stage III/IV disease and were considered high-risk (38 percent) or high-intermediate risk (62 percent). Key findings presented by Dr. Nancy Bartlett from the Washington University, Siteman Cancer Center in St. Louis, MO, included:
- Of 51 evaluable patients across both dose cohorts, 41 patients (80 percent) obtained an objective response, including 34 patients (67 percent) with a complete remission and seven patients (14 percent) with a partial remission. Five patients (10 percent) had progressive disease. Five patients did not have end of treatment assessments. The estimated PFS rate at six months was 79 percent and at 12 months was 65 percent.
- Antitumor activity was not significantly different between the two dosage arms.
- Of 25 evaluable patients who had CD30-positive disease, 21 patients (84 percent) obtained an objective response, including 19 patients (76 percent) with a complete remission and two patients (eight percent) with a partial remission. The estimated PFS rate for CD30-positive patients at both six and 12 months was 86 percent.
- Of 23 evaluable patients who had CD30-undetectable disease, 19 patients (83 percent) obtained an objective response, including 14 patients (61 percent) with a complete remission and five patients (22 percent) with a partial remission. The estimated PFS rate for CD30-undetectable patients at six months was 81 percent and at 12 months was 58 percent.
- These data demonstrate that among CD30-positive DLBCL patients, the complete remission rate was higher (76 versus 61 percent) and the estimated PFS at 12 months was higher (86 versus 58 percent) compared to patients with undetectable CD30 by immunohistochemistry testing.
- The most common treatment-emergent adverse events of any grade for patients treated in the 1.2 mg/kg and 1.8 mg/kg combination cohorts, respectively, were fatigue (55 and 68 percent), peripheral sensory neuropathy (55 and 69 percent), nausea (45 and 68 percent), diarrhea (48 and 60 percent) and vomiting (24 and 55 percent).
- The most common Grade 3 or 4 treatment-emergent adverse events for patients treated in the 1.2 mg/kg and 1.8 mg/kg combination cohorts were neutropenia, febrile neutropenia and anemia.
The phase 2 trial is ongoing and was recently expanded to explore the activity and safety of ADCETRIS plus RCHP (omitting vincristine) as a frontline treatment in patients with CD30-positive, high-intermediate or high-risk DLBCL. Separately, ADCETRIS is being evaluated in relapsed or refractory DLBCL. For more information about these trials, visit www.clinicaltrials.gov. ADCETRIS is currently not approved for the treatment of DLBCL.
ADCETRIS is being evaluated broadly in more than 30 ongoing clinical trials, including four phase 3 studies, in earlier lines of its approved HL and sALCL indications as well as in many additional types of CD30-positive malignancies, including cutaneous T-cell lymphoma, B-cell lymphomas and mature T-cell lymphomas.
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 for intravenous injection received accelerated approval from the FDA and approval with conditions from Health Canada for two indications: (1) the treatment of patients with HL after failure of 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 sALCL after failure of at least one prior multi-agent chemotherapy regimen. The indications for ADCETRIS are approved under accelerated approval based on overall response rate. An improvement in patient-reported outcomes or survival has not been established. Continued approval for these indications may be contingent upon verification and description of clinical benefit in confirmatory trials.
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 HL following 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. ADCETRIS has received marketing authorization by regulatory authorities in more than 55 countries. 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 will be solely responsible for development costs.
About Seattle Genetics
Seattle Genetics is a biotechnology company focused on the development and commercialization of innovative antibody-based therapies for the treatment of cancer. Seattle Genetics is leading the field in developing antibody-drug conjugates (ADCs), a technology designed to harness the targeting ability of antibodies to deliver cell-killing agents directly to cancer cells. The company’s lead product, ADCETRIS® (brentuximab vedotin), is a CD30-targeted ADC that, in collaboration with Takeda Pharmaceutical Company Limited, is commercially available for two indications in more than 55 countries, including the U.S., Canada, Japan and members of the European Union. Additionally, ADCETRIS is being evaluated broadly in more than 30 ongoing clinical trials in CD30-expressing malignancies. Seattle Genetics is also advancing a robust pipeline of clinical-stage programs, including SGN-CD19A, SGN-CD33A, SGN-LIV1A, SGN-CD70A, ASG-22ME, ASG-15ME and SEA-CD40. Seattle Genetics has collaborations for its ADC technology with a number of leading biotechnology and pharmaceutical companies, including AbbVie, Agensys (an affiliate of Astellas), Bayer, Genentech, GlaxoSmithKline and Pfizer. More information can be found at www.seattlegenetics.com.
ADCETRIS (brentuximab vedotin) U.S. Important Safety Information
Progressive multifocal leukoencephalopathy (PML): JC virus infection resulting in PML and death can occur in patients receiving ADCETRIS.
ADCETRIS is contraindicated with concomitant bleomycin due to pulmonary toxicity (e.g., interstitial infiltration and/or inflammation).
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. Monitor patients for symptoms of neuropathy, such as hypoesthesia, hyperesthesia, paresthesia, discomfort, a burning sensation, neuropathic pain or weakness and institute dose modifications accordingly.
- Anaphylaxis and infusion reactions: Infusion-related reactions, including anaphylaxis, have occurred with ADCETRIS. Monitor patients during infusion. If an infusion-related reaction occurs, interrupt the infusion and institute appropriate medical management. If anaphylaxis occurs, immediately and permanently discontinue the infusion and administer appropriate medical therapy.
- Hematologic toxicities: Prolonged (≥1 week) severe neutropenia and Grade 3 or 4 thrombocytopenia or anemia can occur with ADCETRIS. Febrile neutropenia has been reported with ADCETRIS. Monitor complete blood counts prior to each dose of ADCETRIS and consider more frequent monitoring for patients with Grade 3 or 4 neutropenia. Monitor patients for fever. If Grade 3 or 4 neutropenia develops, consider dose delays, reductions, discontinuation, or G-CSF prophylaxis with subsequent doses.
- Serious infections and opportunistic infections: Infections such as pneumonia, bacteremia and sepsis or septic shock (including fatal outcomes) have been reported in patients treated with ADCETRIS. Closely monitor patients during treatment for the emergence of possible bacterial, fungal or viral infections.
- Tumor lysis syndrome: Closely monitor patients with rapidly proliferating tumor and high tumor burden.
- Increased toxicity in the presence of severe renal impairment: The frequency of ≥Grade 3 adverse reactions and deaths was greater in patients with severe renal impairment compared to patients with normal renal function. Avoid the use of ADCETRIS in patients with severe renal impairment.
- Increased toxicity in the presence of moderate or severe hepatic impairment: The frequency of ≥Grade 3 adverse reactions and deaths was greater in patients with moderate or severe hepatic impairment compared to patients with normal hepatic function. Avoid the use of ADCETRIS in patients with moderate or severe hepatic impairment.
- Hepatotoxicity: Serious cases of hepatotoxicity, including fatal outcomes, have occurred with ADCETRIS. Cases were consistent with hepatocellular injury, including elevations of transaminases and/or bilirubin, and occurred after the first dose of ADCETRIS or rechallenge. Preexisting liver disease, elevated baseline liver enzymes, and concomitant medications may also increase the risk. Monitor liver enzymes and bilirubin. Patients experiencing new, worsening, or recurrent hepatotoxicity may require a delay, change in dose, or discontinuation of ADCETRIS.
- 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. Hold ADCETRIS if PML is suspected and discontinue ADCETRIS if PML is confirmed.
- Pulmonary toxicity: Pulmonary toxicity has been reported with ADCETRIS. A causal association with single-agent ADCETRIS has not been established. In the event of new or worsening pulmonary symptoms (e.g., cough, dyspnea), perform a prompt diagnostic evaluation and institute appropriate medical therapy.
- Serious dermatologic reactions: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), including fatal outcomes, have been reported with ADCETRIS. If SJS or TEN occurs, discontinue ADCETRIS and administer appropriate medical therapy.
- Embryo-fetal toxicity: Fetal harm can occur. Advise pregnant women of the potential hazard to the fetus.
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.
Concomitant use of strong CYP3A4 inhibitors or inducers, or P-gp inhibitors, has the potential to affect the exposure to monomethyl auristatin E (MMAE).
Use in Specific Populations:
MMAE exposure and adverse reactions are increased in patients with moderate or severe hepatic impairment or severe renal impairment. Avoid use.
For additional Important Safety Information, including Boxed WARNING, please see the full Prescribing Information for ADCETRIS at www.seattlegenetics.com.
Certain of the statements made in this press release are forward looking, such as those, among others, relating to future development activities including clinical trials, and the data from such trials and the therapeutic potential of ADCETRIS. 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 risk of adverse events as ADCETRIS advances in clinical trials, unexpected clinical trial results and regulatory action. 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, 2015, 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.