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Seattle Genetics Announces Additional Analyses of ECHELON-1 and ECHELON-2 Phase 3 Clinical Trials of ADCETRIS® (Brentuximab Vedotin) at the 2019 ASCO Annual Meeting
June 3, 2019 at 8:00 AM EDT
Three-Year Update of ECHELON-1 Trial Continues to Demonstrate Superior Clinical Activity of ADCETRIS in Combination with Chemotherapy when Compared to ABVD in Frontline Hodgkin Lymphoma
Analyses Describe ADCETRIS Activity in T-Cell and B-Cell Non-Hodgkin Lymphomas Across All Levels of CD30 Expression
“We continue to evaluate ADCETRIS as the foundation of care for patients
with CD30-expressing lymphomas,” said
“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,”
Brentuximab Vedotin with Chemotherapy for Stage 3/4 Classical Hodgkin
Lymphoma: 3-year Update of the ECHELON-1 Study (Abstract #7532, poster
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
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
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
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
ADCETRIS received conditional marketing authorization from the
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.
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.
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
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.
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