Seattle Genetics + Takeda announce additional analyses of Adcetris ECHELON-1 phase III Clinical Trial for classical Hodgkin lymphoma.

Seattle Genetics, Inc. and Takeda Pharmaceutical Company Limited announced additional analyses of results from the ECHELON-1 and ECHELON-2 frontline phase III trials of Adcetris (brentuximab vedotin). These analyses were presented at the 61st Annual Meeting of the American Society of Hematology (ASH) taking place December 7-10, 2019 in Orlando, Fla. Adcetris is an antibody-drug conjugate (ADC) directed to CD30, a defining marker of classical Hodgkin lymphoma and expressed on the surface of several types of peripheral T-cell lymphomas (PTCL).

The ECHELON-1 analysis highlighted a four-year update of the phase III clinical trial in a poster presentation. ECHELON-1 is evaluating Adcetris in combination with AVD (Adriamycin [doxorubicin], vinblastine and dacarbazine) compared to ABVD (Adriamycin [doxorubicin], bleomycin, vinblastine and dacarbazine) in patients with Stage III or IV frontline classical Hodgkin lymphoma. The ECHELON-2 phase III clinical trial data were presented in an oral session at ASH and focused on the outcomes of the subset of patients who underwent consolidative stem cell transplant. ECHELON-2 is evaluating Adcetris in combination with CHP (cyclophosphamide, doxorubicin, prednisone) compared to CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) in frontline CD30-expressing PTCL.

�For decades, the standard of care for the treatment of frontline Hodgkin lymphoma has been combination chemotherapy, called ABVD. Unfortunately, approximately 30 percent of patients with advanced stage Hodgkin lymphoma do not respond or relapse following treatment with this therapy,� said Roger Dansey, M.D., Chief Medical Officer at Seattle Genetics. �The four-year update from the ECHELON-1 trial continues to support the robust and durable frontline treatment benefit of Adcetris plus AVD, including in both Stage III and IV disease settings, compared to ABVD across subgroups, regardless of PET2 status. These data reinforce Adcetris plus AVD as a treatment option that should be offered to all newly diagnosed advanced stage patients with Hodgkin lymphoma.�

Brentuximab Vedotin with Chemotherapy for Stage 3/4 Classical Hodgkin Lymphoma (cHL): 4-Year Update of the ECHELON-1 Study (Abstract #4026, poster presentation on Monday, December 9, 2019): 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 progression-free survival (PFS) compared to the control arm of ABVD as assessed by independent review facility (IRF; hazard ratio (HR), 0.77; p=0.035). A four-year post-hoc exploratory analysis was conducted to examine PFS outcomes per investigator assessment in the intent-to-treat population of 1,334 patients, including results by PET2 status, age, stage and prognostic risk scores. Results include: The four-year PFS rate for patients in the Adcetris plus AVD arm was 81.7 percent compared to 75.1 percent in the ABVD arm, a difference of 6.6 percent (HR, 0.69 [95% CI: 0.542, 0.881]). This represents a 31 percent reduction in the risk of progression or death. Median follow-up time was 48.4 months. A PFS benefit at four-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 86.2 percent in the Adcetris plus AVD arm compared to 81.0 percent in the ABVD arm (HR, 0.69), a difference of 5.2 percent. PET2-positive result was 62.1 percent in the Adcetris plus AVD arm compared to 47.7 percent in the ABVD arm (HR, 0.65), a difference of 14.4 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. Notably, improvements compared to ABVD were observed in patients with Stage III (HR, 0.595; [95% CI: 0.386, 0.917]) and Stage IV (HR, 0.745; [95% CI: 0.555, 1.001]) disease.

As previously reported for 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 four-year update shows that among patients with peripheral neuropathy, 83 percent in the Adcetris plus AVD arm and 84 percent in the ABVD arm reported complete resolution or improvement at last follow-up.

Comment: More than 45 countries and regions have approved Adcetris in combination with AVD for the treatment of patients with previously untreated Stage III or IV Hodgkin lymphoma. The FDA approved Adcetris in combination with AVD for the treatment of adult patients with previously untreated stage III or IV classical Hodgkin lymphoma in March 2018, based on the results of the ECHELON-1 phase III clinical trial in which the primary endpoint was modified PFS. In February 2019, the European Commission (EC) approved Adcetris for the treatment of adult patients with previously untreated CD30+ Stage IV Hodgkin lymphoma in combination with AVD.