Efficacy and safety of denileukin diftitox (Dd) in cutaneous T-cell lymphoma (CTCL) patients: Integrated analysis of three large phase III trials

Abstract

8551 Background: ONTAK (Dd), a fusion protein targeting IL-2 receptor in malignant cells, is approved for the treatment of persistent/recurrent CTCL expressing CD25. Dd has been studied in 307 early or advanced stage CTCL patients in three large Phase III trials, Studies #10, #11, #14, the last two recently completed. Integrated efficacy and safety analysis of the trials is presented. Methods: Dd doses were 9 or 18 μg/kg IV, daily for 5 days, repeating every 21 days, up to 8 courses. Patients in Study #10 and #11 were CD25(+) (ie. had CD25 immunostaining in > 20% of malignant cells); Study 14 also included CD25(-) patients. Response confirmation required 3 consecutive courses and was adjudicated by an independent Data Endpoint Review Committee in each trial, using a weighted severity skin, blood and lymph node count. Primary endpoint: Overall Response (ORR, including complete [CR], clinical complete [CCR], or partial [PR] response). Key secondary endpoint: Progression-Free Survival (PFS). Results: Demographics: similar across trials and between arms on each study. Integrated efficacy results are shown in the Table below. Placebo data provides the first detailed measure of spontaneous responses in CTCL patients. Both Dd doses showed significantly better ORR and PFS and lower rates of PD than placebo. Both CD25(+) and CD25(-) patients responded to Dd. Retreated patients also showed significant benefit. Many (70%) Dd responses were confirmed at Course 5 or later. Most AEs were mild or moderate. Grade 3/4 AEs (Dd 74%, Placebo 36%), and SAEs (Dd 41%, Placebo 20%) decreased to placebo levels after course 2 or 3. Conclusions: This analysis represents the largest investigation of a single agent for treatment of CTCL with a placebo arm. The data provide evidence of efficacy and clinical benefit for Dd in all patients with CTCL, regardless of CD25 status. Integrated Efficacy Results Efficacy Endpoint Placebo (N=44) All Dd-treated (N=263) Dd HD CD25(+) (N=118) Dd HD CD25(-) (N=36) Dd Retreated* (N=29) ORR (%) 15.9 38.0** 47.5** 30.6 27.6 CR/CCR 2.3 9.1 11.0 8.3 6.9 PR 13.6 28.9 36.4 22.2 20.7 PD 52.3 17.5 11.0 25.0 34.5 PFS (median days) 124 794** 870** >487** 205** * Patients who responded to Dd on Study 10 or 11, then relapsed and were retreated on Study 14. ** P<0.02 or better compared with Placebo. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Eisai Eisai Eisai Ligand