Seattle Genetics announces additional analyses of ECHELON-1, ECHELON-2 trials
Seattle Genetics announced additional analyses of results from ECHELON-1 and ECHELON-2, the frontline phase 3 trials of ADCETRIS, at the 2019 American Society of Clinical Oncology Annual Meeting. The ECHELON-1 analysis highlights a three-year update of this phase 3 clinical trial evaluating ADCETRIS in combination with AVD compared to ABVD in stage III or IV frontline classical Hodgkin lymphoma patients, including analyses by cycle 2 PET 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 and an analysis of five additional trials in T-cell and B-cell non-Hodgkin lymphomas. ADCETRIS is an antibody-drug conjugate directed to CD30, a defining marker of classical HL and expressed on the surface of several types of PTCL. Brentuximab Vedotin with Chemotherapy for Stage 3/4 Classical Hodgkin Lymphoma: 3-year Update of the ECHELON-1 Study: This poster presentation examines progression-free survival 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. 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, 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, 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, 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: 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 per Blinded Independent Central Review. In addition, overall survival in the ADCETRIS plus CHP arm was statistically significant compared to CHOP. Complete remission rate and objective response rate for the ADCETRIS plus CHP arm were also significantly increased. CD30 expression is a hallmark of systemic anaplastic large cell lymphoma, 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 and PTCL-not otherwise specified 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: 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 by immunohistochemistry. This analysis examined CD30 expression levels of 275 patients across five clinical studies in relapsed or refractory PTCL, cutaneous T-cell lymphoma, 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 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 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.