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Seattle Genetics (NASDAQ: SGEN) - Seattle Genetics Announces Additional Analyses of ECHELON-1 and ECHELON-2 Phase 3 Clinical Trials of ADCETRIS[R] (Brentuximab Vedotin) at the 2019 ASCO Annual Meeting -- 3/6/2019.

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

BOTHELL, Wash. -- (BUSINESS WIRE) -- Jun. 3, 2019 -- Seattle Genetics, Inc. (Nasdaq:SGEN) today announced additional analyses of results from ECHELON-1 and ECHELON-2, the frontline phase 3 trials of ADCETRIS[R] (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:

The three-year PFS for all patients in the ADCETRIS plus AVD arm was 83.1 percent compared to 76 percent in the ABVD arm (HR 0.70), a difference of 7.1 percent.

PFS benefit at three-years for ADCETRIS plus AVD was observed for all patients independent of PET2 status, including in patients who are less than 60 years old.

PET2-negative result was 85.8 percent in the ADCETRIS plus AVD arm compared to 79.5 percent in the ABVD arm (HR 0.69), a difference of 6.3 percent.

PET2-positive result was 67.7 percent in the ADCETRIS plus AVD arm compared to 51.5 percent in the ABVD arm (HR 0.59), a difference of 16.2 percent.

Consistent improvement in PFS was observed among patients treated with ADCETRIS plus AVD compared with ABVD across the majority of pre-specified subgroups, including disease stage, age and prognostic score.

As previously reported at the primary analysis, on the ADCETRIS plus AVD arm, peripheral neuropathy events were observed in 67 percent of patients compared to 43 percent in the ABVD arm. The three-year analysis shows that among patients with peripheral neuropathy, 78 percent of in the ADCETRIS plus AVD arm and 83 percent in the ABVD arm reported complete resolution or improvement at last follow-up.

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:

Among AITL and PTCL-NOS patients, the ORR in patients treated with ADCETRIS plus CHP was independent of the level of CD30 expression. CRs and PRs were observed in patients with all levels of CD30 expression, including those with the lowest level of 10 percent.

The duration of complete response was not associated with CD30 expression level for patients with AITL or PTCL-NOS.

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:

Responses were observed with ADCETRIS treatment in patients with all levels of CD30 expression, including in patients with no detectable CD30 expression by IHC.

Response to ADCETRIS was not associated with CD30 expression level.

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.

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Title Annotation:Media Releases
Publication:US Biotech
Date:Jun 6, 2019
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