Takeda, Seattle Genetics Report Data for Adcetris in Malignant Lymphoma Compared to Prior Theropy

Takeda Pharmaceutical Company Limited and Seattle Genetics, Inc.

today announced data from a post-hoc analysis examining progression-free survival (PFS) following treatment with ADCETRIS^® (brentuximab vedotin) versus last prior therapy in patients diagnosed with relapsed or refractory Hodgkin lymphoma (HL) post-autologous stem cell transplant (ASCT) or relapsed or refractory systemic anaplastic large cell lymphoma (sALCL). The data were highlighted during a presentation at the 12^th International Conference on Malignant Lymphoma (ICML) being held June 19–22, 2013 in Lugano, Switzerland. ADCETRIS is an antibody-drug conjugate (ADC) directed to CD30, a defining marker of classical HL and sALCL. The post-hoc analysis compared investigator assessed PFS following ADCETRIS single-agent treatment to the last prior systemic therapy in patients taking part in two pivotal Phase 2 studies. The post-hoc analysis was conducted in patients with relapsed or refractory HL post-ASCT or relapsed or refractory sALCL in the intent-to-treat (ITT) population. It also included prior systemic treatment histories and post-ADCETRIS stem cell transplant experience for each patient in the ITT populations. “These encouraging data suggest that ADCETRIS may delay disease progression compared to prior therapies used in this heavily pretreated patient population,” said John Radford, M.D., Professor of Medical Oncology, University of Manchester, Manchester, UK. “ADCETRIS is a CD30-targeted treatment option for patients with relapsed or refractory HL or relapsed or refractory sALCL that has shown a high overall response rate, including durable complete responses in both of its approved indications.” Progression-free survival analyses of two pivotal phase 2 studies of brentuximab vedotin in patients with relapsed or refractory Hodgkin lymphoma or systemic anaplastic large-cell lymphoma (Poster #303) The analysis, presented by Dr. Radford, included: Relapsed or Refractory HL post-ASCT * 102 patients (median age 31 years) diagnosed with relapsed or refractory HL post-ASCT received a median of 3.5 (range, 1–13) prior chemotherapy regimens, not including ASCT, prior to enrollment in the study * 91 percent of patients received doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD) as front-line therapy * Approximately one-half of patients received ifosfamide, carboplatin, etoposide (ICE) as second-line therapy * There was no discernible pattern in terms of treatment regimens after second-line therapy * As expected this was a very heavily pretreated population prior to study entry * 62 percent of patients achieved a longer PFS with ADCETRIS than with their last prior therapy at a median follow-up of 27 months * Median PFS was 9.3 months (range, 1.2–36.4) with ADCETRIS versus 6.1 months (range, 1.0–110.2) with last prior therapy * 63 percent of patients who relapsed within six months of their most recent ASCT and 65 percent of patients who relapsed within twelve months of their most recent ASCT achieved a longer PFS with ADCETRIS than with their last prior systemic therapy * 20 patients underwent a stem cell transplant (STC) after receiving ADCETRIS, including: * ASCT (1 patient), allogeneic SCT (18 patients), ASCT followed by allogeneic SCT (1 patient) * 7 patients received a transplant after treatment with ADCETRIS alone Relapsed or Refractory sALCL * 58 patients (median age 52 years) diagnosed with relapsed or refractory sALCL received a median of 2 (range, 1–6) prior chemotherapy regimens, not including ASCT, prior to their enrollment into the study * Cyclophosphamide, hydroxy doxorubicin, Oncovin^®, prednisone (CHOP) was the most commonly used regimen (72 percent) in patients, either as first-line induction therapy or as maintenance therapy * Most agents were given as part of a combination regimen * 67 percent of patients achieved a longer PFS with ADCETRIS than with their last prior therapy at a median follow-up 22 months * Median PFS was 19.6 months (range, 0.8–29.0) with ADCETRIS versus 5.9 months (range, 0.3–111.9) with the last prior therapy * 20 patients underwent a SCT after receiving ADCETRIS, including: * ASCT (9 patients) and allogeneic SCT (11 patients) * 17 patients received a transplant after treatment with ADCETRIS alone Details of the poster presentation are as follows: * Poster available on June 19, 2013 12:00 PM CET * Poster #303 * First author: John Radford, M.D., Professor of Medical Oncology, University of Manchester, Manchester, UK Additional oral and poster presentations featured at ICML about ADCETRIS include: * Objective responses in relapsed B-cell lymphomas with single-agent brentuximab vedotin * Poster session on Thursday, June 20, 2013 from 8:30 AM - 6:30 PM CET * Abstract #304 * First author: Eric D. Jacobsen, M.D., Dana-Farber Cancer Institute, Boston, MA * ECHELON-2: phase 3 trial of brentuximab vedotin and CHP versus CHOP in the frontline treatment of patients (pts) with CD30+ mature T-cell lymphomas (MTCL) * Oral session on Friday, June 21, 2013 at 5:25 PM CET * Abstract #138 * First author: Owen A. O'Connor, M.D., Ph.D., Professor, and Director, Division of Hematology and Medical Oncology at NYU Cancer Institute, New York, NY * Two-year follow up of patients with relapsed/refractory Hodgkin treated with brentuximab vedotin prior to reduced intensity allogeneic hematopoietic cell transplantation * Oral session on Saturday, June 22, 2013 at 8:40 AM CET * Abstract #140 * First author: Robert Chen, M.D., City of Hope National Medical Center. Duarte, CA * PET-adapted sequential therapy with brentuximab vedotin and augmented-ICE induces FDG-PET normalization in 92% of patients with relapsed and refractory Hodgkin lymphoma * Oral session on Saturday, June 22, 2013 at 8:50 AM CET * Abstract #141 * First author: Alison J. Moskowitz, M.D., Memorial Sloan-Kettering Cancer Center, New York, NY * Safety and efficacy of brentuximab vedotin for treatment of relapsed mature T-/NK-cell lymphomas * Oral session on Saturday, June 22, 2013 at 10:00 AM CET * Abstract #152 * First author: Yasuhiro Oki, M.D., Department of Lymphoma/Myeloma, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX About ADCETRIS^® (brentuximab vedotin) ADCETRIS^® (brentuximab vedotin) is the first and only targeted CD30 antibody-drug conjugate (ADC) being evaluated in a variety of CD30-expressing malignancies including Hodgkin lymphoma (HL) and systemic anaplastic large cell lymphoma (sALCL). The ADC utilizes Seattle Genetics' proprietary technology, which employs a linker system designed to be stable in the bloodstream but to release monomethyl auristatin E (MMAE) upon internalization into CD30-expressing tumor cells. ADCETRIS was granted conditional marketing authorization by the European Commission in October 2012 for two indications: (1) for the treatment of adult patients with relapsed or refractory CD30-positive HL following autologous stem cell transplant (ASCT), or following at least two prior therapies when ASCT or multi-agent chemotherapy is not a treatment option, and (2) the treatment of adult patients with relapsed or refractory sALCL. ADCETRIS also received marketing authorization by regulatory authorities in Switzerland and South Korea. ADCETRIS was granted accelerated approval by the U.S. Food and Drug Administration (FDA) and approval with conditions from Health Canada for two indications: (1) the treatment of patients with HL after failure of autologous stem cell transplant (ASCT) or after failure of at least two prior multi-agent chemotherapy regimens in patients who are not ASCT candidates, and (2) the treatment of patients with sALCL after failure of at least one prior multi-agent chemotherapy regimen. The indications for ADCETRIS are based on response rate. There are no data available demonstrating improvement in patient-reported outcomes or survival with ADCETRIS.