984TiP - Phase 3 trial of brentuximab vedotin and CHP versus CHOP in the frontline treatment of patients (pts) with CD30+ mature T-cell lymphomas (MTCL)

Date 28 September 2014
Event ESMO 2014
Session Poster Display session
Topics Anti-Cancer Agents & Biologic Therapy
Lymphomas
Presenter Tim Illidge
Citation Annals of Oncology (2014) 25 (suppl_4): iv327-iv339. 10.1093/annonc/mdu339
Authors T. Illidge1, B. Pro2, L.H. Trümper3, E.K. Larsen4, D. Huebner5, D.A. Kennedy6, O. O'Connor7
  • 1Medical Oncology/hematology, Christie Hospital NHS, M20 4BX - Manchester/GB
  • 2Medical Oncology/hematology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia/US
  • 3Medical Oncology/hematology, Georg-August University, Göttingen/DE
  • 4Biostatistics, Seattle Genetics, Inc, Bothell/US
  • 5Clinical Development, Takeda Pharmaceuticals International Co., Cambridge/US
  • 6Clinical Affairs, Seattle Genetics, Inc., Bothell/US
  • 7Medical Oncology Hematology, Columbia University Medical Center, New York Presbyterian Hospital, New York/US

Abstract

Background

MTCL including systemic anaplastic large cell lymphoma (sALCL) are aggressive neoplasms. Anthracycline-based multiagent chemotherapy regimens have demonstrated response rates ranging from 76 to 88%. Five-year overall survival rates range from 12 to 49% depending on the histologic subtype. Brentuximab vedotin is an antibody drug conjugate that has shown efficacy in a pivotal phase 2 study as a single agent in relapsed sALCL (Pro et al., J Clin Oncol, 2012) and evidence of clinical activity in combination with CHP in the frontline treatment of MTCL including sALCL in a phase 1 study (Fanale et al., ASH 2012).

Trial design

This randomized, double-blind, placebo-controlled, multicenter, phase 3 study (NCT01777152) is evaluating the safety and efficacy of 1.8 mg/kg brentuximab vedotin with CHP (A + CHP) vs CHOP for frontline treatment of CD30+ MTCL. Pts must have FDG-avid disease by PET and measureable disease of at least 1.5 cm by CT. Approximately 300 pts will be randomized 1:1 to receive A + CHP or CHOP for 6–8 cycles (q3wk). Randomization will be stratified by ALK+ sALCL vs other histologic subtypes and IPI score (0–1, 2–3, or 4–5). The target proportion of pts with a diagnosis of sALCL will be 75%. The primary objective is to compare progression-free survival (PFS) between the 2 treatment arms as determined by an independent review facility (IRF). Secondary objectives include comparisons of PFS per IRF in sALCL patients, safety, overall survival, and complete remission rate between the 2 arms. After completion of treatment, pts will be followed for disease progression, medical resource utilization, quality of life, and survival. Post-treatment stem cell transplant is permitted. Efficacy assessments will use the Revised Response Criteria for Malignant Lymphoma (Cheson 2007). CT and PET scans will be performed at baseline, after Cycle 4, and after the completion of treatment. CT scans will also be performed at regular intervals during follow-up until disease progression, death, or analysis of the primary endpoint. Safety assessments will occur throughout the study until 30 days after last dose of study treatment. Enrollment for this global trial is ongoing. Reused with permission from the American Society of Clinical Oncology (ASCO). This abstract was accepted and previously presented at the 2013 ASCO Annual Meeting. All rights reserved. ASCO 2013 (TPS8611).

Disclosure

T. Illidge: Consultant: Takeda Pharmaceuticals International Co., Seattle Genetics, Inc. Honoraria: Takeda Pharmacueticals International Co. Research funding/grants: Seattle Genetics, Inc.; B. Pro: Acted as a consultant for: Seattle Genetics, Inc. Research funding/grants provided to the authors institution by: Seattle Genetics, Inc.; L.H. Trümper: Acted as a consultant for: Seattle Genetics, Inc.; E.K. Larsen: Employment: Seattle Genetics, Inc. Equity ownership (including stock options): Seattle Genetics, Inc.; D. Huebner: Employment: Takeda Pharmaceuticals International Co. Equity ownership (including stock options): Takeda Pharmaceuticals International Co.; D.A. Kennedy: Employment: Seattle Genetics, Inc.; Equity ownership (including stock options): Seattle Genetics, Inc.; O. O'Connor: Consultant: Onyx, Takeda Pharmaceuticals International Co., Celgene, Allos, Seattle Genetics, Inc. Honoraria: Takeda Pharmacueticals International Co. Research funding/grants: Seattle Genetics, Inc. Takeda Pharmacueticals International Co., Allos.