THE EFFICACY OF DUVELISIB MONOTHERAPY FOLLOWING DISEASE PROGRESSION ON OFATUMUMAB MONOTHERAPY IN PATIENTS WITH RELAPSED/REFRACTORY CLL OR SLL IN A PHASE 3 CROSSOVER EXTENSION STUDY
Author(s): ,
Peter Hillman
Affiliations:
St. James's Institute of Oncology, The Leeds Teaching Hospitals,Leeds,United Kingdom
,
Bryone Kuss
Affiliations:
Flinders Medical Centre (FMC),Bedford Park,Austria
,
Carol Moreno
Affiliations:
Department of Hematology ,Hospital de Sant Pau i Santa Creu, Autonomous University of Barcelona,Barcelona,Spain
,
Matthew Davids
Affiliations:
Department of Medical Oncology,Dana-Farber Cancer Institute,Boston,United States
,
Nicole Lammana
Affiliations:
New York Presbyterian,Columbia University Medical Center,New York,United States
,
Zsolt Nagy
Affiliations:
1st Department of Internal Medicine,Semmelweis University,Budapest,Hungary
,
James Essell
Affiliations:
OHC ,Cincinnati ,United States
,
Paolo Ghia
Affiliations:
Università Vita-Salute San Raffaele and IRCCS Istituto Scientifico San Raffaele,Milan,Italy
,
Constantine Tam
Affiliations:
Peter MacCallum Cancer Centre,Melbourne,Australia
,
Ulrich Jaeger
Affiliations:
Medical University of Vienna,Vienna,Austria
,
Stephan Stilgenbauer
Affiliations:
Department III of Internal Medicine,University Hospital Ulm,Ulm,Germany
,
Julio Delgado
Affiliations:
Hospital Clinic,Barcelona,Spain
,
NgocDiep Le
Affiliations:
Verastem, Inc,Needham,United States
,
Brenda Jeglinski
Affiliations:
Verastem, Inc,Needham,United States
Marco Montillo
Affiliations:
Niguarda Cancer Center,ASST Grande Ospedale Metropolitano Niguarda,Milan,Italy
EHA Library. Hillman P. Jun 15, 2018; 214827; PF354
Peter Hillman
Peter Hillman
Contributions
×
Abstract

Abstract: PF354

Type: Poster Presentation

Presentation during EHA23: On Friday, June 15, 2018 from 17:30 - 19:00

Location: Poster area

Background
Duvelisib, an oral dual inhibitor of PI3K-δ, γ, is being developed for the treatment of hematologic malignancies, including relapsed/refractory (RR) CLL/SLL. In the Phase 3 DUO study (NCT02004522) duvelisib monotherapy demonstrated significant improvement compared to ofatumumab monotherapy (PFS 13.3 vs 9.9 mo. p<0.0001; ORR 74% vs 45% p <0.0001) with a manageable safety profile (Flinn, ASH 2017). Study IPI-145-12 (NCT02049515) is an open-label, optional, crossover extension study where pts with confirmed progressive disease (PD) on DUO were given the option to receive the opposite treatment. 

Aims
Herein we present data for the 89 pts who voluntarily rolled over following PD on ofatumumab on DUO and received duvelisib on Study IPI-145-12.

Methods
Eligible pts were enrolled within 3 months of PD on the DUO study (excluding Richter’s transformation or prolymphocytic leukemia), and maintained adequate renal and hepatic function and an ECOG PS of 0-2. Duvelisib 25 mg BID was administered until PD, intolerance, death, or study withdrawal. Responses were determined by investigators per modified IWCLL/IWG criteria. 

Results
Median age was 68 yrs (range: 39-89), 63% were male, and 90% Caucasian. Nearly half (49%) had Rai Stage III/IV or Binet Stage C, and 23% had del(17p) and/or TP53 mutation. Median prior anticancer therapies was 3 (range: 2-8). Median exposure to duvelisib was 32 weeks on the extension study. The ORR for pts treated with duvelisib in the crossover was 73% (95% CI: 64, 82) (all PRs) compared to 28% (95% CI: 19, 37) (1% CR, 27% PR) when previously treated with ofatumumab in DUO. The median PFS for duvelisib was 15 mo. (95% CI: 10, 17) compared to 9 mo. (95% CI: 9, 11) for prior ofatumumab. 

Conclusion
In an extension study, duvelisib monotherapy achieved robust and durable responses in 89 RR CLL/SLL pts with PD following ofatumumab treatment in the DUO study (ORR: duvelisib 73%; prior ofatumumab 28%), with a longer PFS with duvelisib than prior ofatumumab (PFS: duvelisib 15 mo.; prior ofatumumab 9 mo.). These data further support duvelisib monotherapy as an effective oral treatment option for pts with RR CLL/SLL.

Session topic: 6. Chronic lymphocytic leukemia and related disorders - Clinical

Keyword(s): Chronic Lymphocytic Leukemia, Phase III, PI3K

By clicking “Accept Terms & all Cookies” or by continuing to browse, you agree to the storing of third-party cookies on your device to enhance your user experience and agree to the user terms and conditions of this learning management system (LMS).

Cookie Settings
Accept Terms & all Cookies