Seattle Genetics, Inc. (Nasdaq:SGEN) today highlighted data from the ECHELON-1 phase 3 clinical trial evaluating ADCETRIS (brentuximab vedotin) in combination with AVD (Adriamycin®, vinblastine and dacarbazine) in newly diagnosed stage III or IV classical Hodgkin lymphoma (HL) at the 60th American Society of Hematology (ASH) Annual Meeting and Exposition taking place in San Diego, Calif., December 1-4, 2018. In March 2018, the U.S. Food and Drug Administration (FDA) approved ADCETRIS in combination with AVD for the treatment of adult patients with previously untreated stage III or IV classical HL based on the positive results of the ECHELON-1 phase 3 clinical trial. ADCETRIS is an antibody-drug conjugate (ADC) directed to CD30, a defining marker of classical HL that plays a role in tumor growth and survival.
“Prior to the FDA approval of ADCETRIS in combination with AVD, up to 30 percent of patients with advanced stage classical Hodgkin lymphoma would not respond or would relapse following frontline treatment with ABVD, demonstrating a need for more effective treatment options,” said Roger Dansey, M.D., Chief Medical Officer at Seattle Genetics. “Additional analyses from the ECHELON-1 phase 3 clinical trial show that with an additional 18 months of follow-up, the benefit of ADCETRIS plus AVD was maintained compared to ABVD. Select presentations at the ASH Annual Meeting underscore the benefit of ADCETRIS plus AVD in frontline advanced stage HL.”
Three poster presentations highlight analyses from the ECHELON-1 phase 3 clinical trial evaluating ADCETRIS in combination with AVD compared to ABVD (Adriamycin, bleomycin, vinblastine and dacarbazine) in stage III or IV frontline classical HL patients. The ECHELON-1 poster presentations include an analysis of efficacy benefit for ADCETRIS plus AVD regardless of the inclusion of modified events and progression-free survival (PFS) outcomes in patients per investigator, as well as results of the adolescents and young adults (AYA) trial participants. In addition, data will be presented on peripheral neuropathy resolution and improvement for patients treated with ADCETRIS plus AVD or ABVD after 30 months of follow-up.
Brentuximab Vedotin plus Chemotherapy in Patients with Advanced-Stage Classical Hodgkin Lymphoma: Evaluation of Modified Progression-Free Survival and Traditional PFS in the Phase 3 ECHELON-1 Study (Abstract #2904, poster presentation on Sunday, December 2, 2018)
As previously reported, the ECHELON-1 trial achieved its primary endpoint with the combination of ADCETRIS plus AVD resulting in a statistically significant improvement in modified PFS versus the control arm of ABVD as assessed by independent review facility (IRF; HR 0.77; p-value=0.035). Modified PFS was defined as time to progression, death, or evidence of non-complete response after completion of frontline therapy per IRF followed by subsequent anticancer therapy. An analysis was conducted to examine PFS outcomes at three-years and evaluate how the inclusion of subsequent therapy as modified events affected efficacy outcomes in the ECHELON-1 study. Key findings will be presented in a poster presentation by Joseph M. Connors, M.D., FRCPC, Clinical Director, Center for Lymphoid Cancer at BC Cancer in Vancouver, Canada, and include:
Brentuximab Vedotin with Chemotherapy in Adolescents and Young Adults (AYA) with Stage III or IV Hodgkin Lymphoma: a Subgroup Analysis From the Phase 3 ECHELON-1 Study (Abstract #1647, poster presentation on Saturday, December 1, 2018)
Of the 1,334 advanced stage classical HL patients who participated in the ECHELON-1 clinical trial, 771 patients (57.8 percent) were AYA defined as age 15 to 39 years, with 396 patients in the ADCETRIS plus AVD arm and 375 patients in the ABVD control arm. To participate in the ECHELON-1 study, trial participants had to be 18 years or older. The median age of patients in the ADCETRIS plus AVD arm compared to the control arm was 27 years and 28 years, respectively. Key findings were presented in a poster presentation by Howland Crosswell, M.D., Pediatric Hematology-Oncology at the Bon Secours Hematology Oncology in Greenville, S.C., and include:
Resolution of Peripheral Neuropathy (PN) in Patients Who Received A+AVD or ABVD in the Phase 3 ECHELON-1 Trial (Abstract #2921, poster presentation on Sunday, December 2, 2018)
As previously reported in the ECHELON-1 study, the incidence of peripheral neuropathy of any grade was 67 percent (442 of 662 patients) and 43 percent (286 of 659 patients) in the ADCETRIS plus AVD and ABVD arms of the study, respectively. At the time of primary analysis and with a median follow-up time of approximately 21 months, 67 percent of patients treated with ADCETRIS plus AVD had either complete resolution or improvement of peripheral neuropathy events by at least one grade at the time of last follow-up. An updated analysis of peripheral neuropathy outcomes from the ECHELON-1 study at a median follow-up time of 30 months will be presented in a poster presentation by John Radford, M.D., Manchester Academic Health Centre in Manchester, United Kingdom, and include:
About ADCETRIS (brentuximab vedotin)
ADCETRIS is being evaluated broadly in more than 70 clinical trials in CD30-expressing lymphomas. These include three recently completed phase 3 trials: ECHELON-2 in frontline peripheral T-cell lymphomas (also known as mature T-cell lymphoma), ECHELON-1 in previously untreated Hodgkin lymphoma, and ALCANZA in cutaneous T-cell lymphoma. The phase 3 CHECKMATE 812 trial of ADCETRIS in combination with Opdivo (nivolumab) for relapsed/refractory Hodgkin lymphoma is ongoing.
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 six indications in adult patients with: (1) previously untreated systemic anaplastic large cell lymphoma (sALCL) or other CD30-expressing peripheral T-cell lymphomas (PTCL), including angioimmunoblastic T-cell lymphoma and PTCL not otherwise specified, in combination with cyclophosphamide, doxorubicin, and prednisone, (2) previously untreated Stage III or IV classical Hodgkin lymphoma (cHL), in combination with doxorubicin, vinblastine, and dacarbazine, (3) cHL at high risk of relapse or progression as post-autologous hematopoietic stem cell transplantation (auto-HSCT) consolidation, (4) cHL after failure of auto-HSCT or failure of at least two prior multi-agent chemotherapy regimens in patients who are not auto-HSCT candidates, (5) sALCL after failure of at least one prior multi-agent chemotherapy regimen, and (6) primary cutaneous anaplastic large cell lymphoma (pcALCL) or CD30-expressing mycosis fungoides (MF) who have received prior systemic therapy.
Health Canada granted ADCETRIS approval with conditions for relapsed or refractory Hodgkin lymphoma and sALCL in 2013, and non-conditional approval for post-autologous stem cell transplantation (ASCT) consolidation treatment of Hodgkin lymphoma patients at increased risk of relapse or progression.
ADCETRIS received conditional marketing authorization from the European Commission in October 2012. The approved indications in Europe are: (1) for the treatment of adult patients with relapsed or refractory CD30-positive Hodgkin lymphoma following ASCT, or following at least two prior therapies when ASCT or multi-agent chemotherapy is not a treatment option, (2) the treatment of adult patients with relapsed or refractory sALCL, (3) for the treatment of adult patients with CD30-positive Hodgkin lymphoma at increased risk of relapse or progression following ASCT, and (4) for the treatment of adult patients with CD30-positive cutaneous T-cell lymphoma (CTCL) after at least one prior systemic therapy.
ADCETRIS has received marketing authorization by regulatory authorities in 72 countries for relapsed or refractory Hodgkin lymphoma and sALCL. See select important safety information, including Boxed Warning, 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.
About Seattle Genetics
Seattle Genetics, Inc. is an emerging multi-product, global biotechnology company that develops and commercializes transformative therapies targeting cancer to make a meaningful difference in people’s lives. ADCETRIS® (brentuximab vedotin) utilizes the company’s industry-leading antibody-drug conjugate (ADC) technology and is currently approved for the treatment of multiple CD30-expressing lymphomas. Beyond ADCETRIS, the company has established a pipeline of novel targeted therapies at various stages of clinical testing, including three in ongoing pivotal trials for solid tumors. Enfortumab vedotin for metastatic urothelial cancer and tisotumab vedotin for metastatic cervical cancer utilize our proprietary ADC technology. Tucatinib, a small molecule tyrosine kinase inhibitor, is in a pivotal trial for HER2-positive metastatic breast cancer. In addition, we are leveraging our expertise in empowered antibodies to build a portfolio of proprietary immuno-oncology agents in clinical trials targeting hematologic malignancies and solid tumors. The company is headquartered in Bothell, Washington, and has a European office in Switzerland. For more information on our robust pipeline, visit www.seattlegenetics.com and follow @SeattleGenetics on Twitter.
ADCETRIS (brentuximab vedotin) Important Safety Information
BOXED WARNING: PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY (PML):
JC virus infection resulting in PML and death can occur in ADCETRIS-treated patients.
Contraindication
ADCETRIS concomitant with bleomycin due to pulmonary toxicity (e.g., interstitial infiltration and/or inflammation).
Warnings and Precautions
Most Common (≥20% in any study) Adverse Reactions: Peripheral neuropathy, fatigue, nausea, diarrhea, neutropenia, upper respiratory tract infection, pyrexia, constipation, vomiting, alopecia, decreased weight, abdominal pain, anemia, stomatitis, lymphopenia and mucositis.
Drug Interactions
Concomitant use of strong CYP3A4 inhibitors or inducers has the potential to affect the exposure to monomethyl auristatin E (MMAE).
Use in Specific Populations
Moderate or severe hepatic impairment or severe renal impairment: MMAE exposure and adverse reactions are increased. Avoid use.
Advise males with female sexual partners of reproductive potential to use effective contraception during ADCETRIS treatment and for at least 6 months after the final dose of ADCETRIS.
Advise patients to report pregnancy immediately and avoid breastfeeding while receiving ADCETRIS.
For additional Important Safety Information, including BOXED WARNING, please see the full Prescribing Information for ADCETRIS at www.seattlegenetics.com or http://www.ADCETRIS.com.
Seattle Genetics Forward Looking Statements
Certain of the statements made in this press release are forward looking, such as those, among others, relating to the potential benefit and use of ADCETRIS (brentuximab vedotin). Actual results or developments may differ materially from those projected or implied in these forward-looking statements due to factors such as utilization and adoption of the approved treatment regimen by prescribing physicians, competitive conditions including the availability of alternative treatment regimens, the availability and extent of reimbursement, the risk of adverse events, and adverse regulatory action. More information about the risks and uncertainties faced by Seattle Genetics is contained under the caption “Risk Factors” included in the company’s Quarterly Report on Form 10-Q for the quarter ended September 30, 2018 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.
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