Seattle Genetics, Inc. (Nasdaq:SGEN) today announced additional analyses of results from ECHELON-1 and ECHELON-2, the frontline phase 3 trials of ADCETRIS® (brentuximab vedotin), at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting taking place May 31 to June 4, 2019 in Chicago. The ECHELON-1 analysis highlights a three-year update of this phase 3 clinical trial evaluating ADCETRIS in combination with AVD (Adriamycin, vinblastine and dacarbazine) compared to ABVD (Adriamycin, bleomycin, vinblastine and dacarbazine) in stage III or IV frontline classical Hodgkin lymphoma (HL) patients, including analyses by cycle 2 PET (PET2) status and in patients less than 60 years old. In addition, two poster presentations evaluate CD30 expression and response to ADCETRIS treatment in the ECHELON-2 phase 3 clinical trial in peripheral T-cell lymphomas (PTCL) and an analysis of five additional trials in T-cell and B-cell non-Hodgkin lymphomas (NHL). ADCETRIS is an antibody-drug conjugate (ADC) directed to CD30, a defining marker of classical HL and expressed on the surface of several types of PTCL.
“We continue to evaluate ADCETRIS as the foundation of care for patients with CD30-expressing lymphomas,” said Roger Dansey, M.D., Chief Medical Officer at Seattle Genetics. “Importantly, the ECHELON-1 three-year analysis presented at this meeting demonstrate a robust and durable treatment benefit of ADCETRIS plus AVD versus ABVD across most subgroups and regardless of PET status. In addition, other ADCETRIS presentations at the ASCO Meeting include new analyses evaluating response by CD30 expression across several non-Hodgkin lymphoma studies.”
“Tumor expression of CD30 by IHC in B-cell and T-cell non-Hodgkin lymphomas can be quite variable between different patients with the same diagnosis and even between different biopsies within the same patient,” said Steven Horwitz, M.D., Department of Medicine, Lymphoma Service, Memorial Sloan Kettering Cancer Center, New York, and an ADCETRIS clinical trial investigator. “In two poster presentations at this year’s ASCO Annual Meeting, results of the analyses suggest that a lower limit or threshold of CD30 expression required for efficacy has not been identified and individual patients may experience clinical benefit from brentuximab vedotin regardless of the level of CD30 expression.”
Brentuximab Vedotin with Chemotherapy for Stage 3/4 Classical Hodgkin Lymphoma: 3-year Update of the ECHELON-1 Study (Abstract #7532, poster presentation on Monday, June 3, 2019)
This poster presentation examines progression-free survival (PFS) outcomes per investigator assessment in the intent-to-treat population of 1,334 patients at three-years by PET status and in patients less than 60 years old. 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; hazard ratio [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. Key findings from these analyses include:
Response to A+CHP by CD30 Expression in the ECHELON-2 Trial (Abstract #7538, poster presentation on Monday, June 3, 2019)
As previously reported, the ECHELON-2 trial met its primary endpoint with the combination of ADCETRIS plus CHP resulting in a statistically significant improvement in PFS versus the control arm of CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) per Blinded Independent Central Review (HR=0.71; p-value=0.0110). In addition, overall survival in the ADCETRIS plus CHP arm was statistically significant compared to CHOP (HR=0.66; p-value=0.0244). Complete remission (CR) rate (p-value=0.0066) and objective response rate (ORR; p-value=0.0032) for the ADCETRIS plus CHP arm were also significantly increased. CD30 expression is a hallmark of systemic anaplastic large cell lymphoma (sALCL), but it is variably expressed among non-sALCL PTCL subtypes. As a lack of correlation between CD30 expression and response to ADCETRIS has been previously reported, an analysis was conducted to examine response to ADCETRIS plus CHP by CD30 expression in 57 patients with angioimmunoblastic T-cell lymphoma (AITL) and PTCL-not otherwise specified (PTCL-NOS) in the ECHELON-2 study, the two histologies with variable expression. Key findings of this exploratory analysis include:
Response to Brentuximab Vedotin by CD30 Expression: Results from Five Trials in PTCL, CTCL, and B-cell Lymphomas (Abstract #7543, poster presentation on Monday, June 3, 2019)
Exploratory analyses were conducted to examine the correlation between pretreatment CD30 expression level and ORR for patients with CD30 expression greater than or equal to 10 percent, less than 10 percent, or undetectable (0 percent) by immunohistochemistry (IHC). This analysis examined CD30 expression levels of 275 patients across five clinical studies in relapsed or refractory PTCL, cutaneous T-cell lymphoma (CTCL), and B-cell NHL. All patients in this analysis were treated with ADCETRIS monotherapy. The key findings include:
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 in March 2018, based on the results of the ECHELON-1 phase 3 clinical trial. The FDA approved ADCETRIS in combination with CHP (cyclophosphamide, doxorubicin, and prednisone) for the treatment of adult patients with previously untreated sALCL or other CD30-expressing PTCL, including AITL and PTCL-NOS based on the results of the ECHELON-2 phase 3 trial, in November 2018.
About ADCETRIS
ADCETRIS is being evaluated broadly in more than 70 clinical trials in CD30-expressing lymphomas. These include three completed phase 3 trials: ECHELON-2 trial in frontline peripheral T-cell lymphomas, ECHELON-1 in previously untreated Hodgkin lymphoma, and ALCANZA in cutaneous T-cell lymphoma. The 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 in 2017, adults with pcALCL or CD30-expressing MF who have had prior systemic therapy in 2018, and for previously untreated Stage IV Hodgkin lymphoma in combination with doxorubicin, vinblastine, and dacarbazine in 2019.
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) for 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, (4) for the treatment of adult patients with CD30-positive cutaneous T-cell lymphoma (CTCL) after at least one prior systemic therapy and (5) for the treatment of adult patients with previously untreated CD30-positive Stage IV Hodgkin lymphoma in combination with AVD (Adriamycin®, vinblastine and dacarbazine).
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) U.S. 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.
Forward-Looking Statements
Certain of the statements made in this press release are forward looking, such as those, among others, relating to the possible uses and benefits of ADCETRIS as the foundation of care for CD30-expressing lymphomas and in certain clinical settings. 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 potential lack of efficacy or risk of adverse events associated with the use of ADCETRIS in certain clinical settings. 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 March 31, 2019 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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