231 Updated Analysis of Overall Survival in Randomized Phase III

Study of Idelalisib in Combination with Bendamustine and Rituximab

in Patients with Relapsed/Refractory CLL
CLL: Therapy, excluding Transplantation
Program: Oral and Poster Abstracts
Type: Oral
Session: 642. CLL: Therapy, excluding Transplantation: Maintenance Therapy and Long-Term
Follow-Up Targeted Therapy Trials
Saturday, December 3, 2016: 4:30 PM
Room 5AB (San Diego Convention Center)
Andrew D Zelenetz, MD, PhD1, Jennifer R. Brown2, Julio Delgado3*, Herbert Eradat4, Paolo Ghia5,
Abraham Jacob6*, Wojciech Jurczak7, Javier Loscertales8*, Donald MacDonald9*, Franck
Morschhauser, MD, PhD10*, Javier De la Serna11, Mazyar Shadman12,13*, Christopher Pocock14,
Adeboye Henry Adewoye15, Yeonhee Kim15*, David Simpson16 and Stephan Stilgenbauer17
1Memorial Sloan Kettering Cancer Center, New York, NY
2CLL Center, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA
3Department d'Hematologia, Hospital Clinic, Institut d'Investigacions Biomdiques August Pi i Sunyer (IDIBAPS),

Barcelona, Spain
4Division of Hematology-Oncology, David Geffen School of Medicine at UCLA, Los Angeles, CA

5Division of Experimental Oncology and Department of Onco-Hematology, Universit Vita-Salute San Raffaele and

IRCCS San Raffaele Scientific Institute, Milan, Italy

6Royal Wolverhampton Hospitals NHS Trust New Cross Hospital, Wolverhampton, United Kingdom

7Department of Haematology, Jagiellonian University, Krakw, Poland

8Department of Haematology, Hospital Universitario de La Princesa, IIS-IP, Madrid, Spain

9Centre for Haematology, Imperial College London, Hammersmith Hospital, London, United Kingdom

10Service des Maladies du Sang, Hpital Huriez, Universit de Lille, Unit Groupe de Recherche sur les formes Injectables

et les Technologies Associes, Lille, France

11Servicio de Hematologa, Hospital Universitario 12 de Octubre, Madrid, Spain

12Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA

13Department of Medicine, University of Washington, Seattle, WA

14East Kent Hospitals, Canterbury, United Kingdom

15Gilead Sciences, Inc., Foster City, CA

16North Shore Hospital, Auckland, New Zealand

17Department of Internal Medicine III, Ulm University, Ulm, Germany

Introduction: Therapies able to improve overall survival in patients with relapsed/refractory (RR) CLL
are needed. We have previously reported that idelalisib (IDELA), a selective PI3K delta inhibitor,
administered in combination with bendamustine/rituximab (BR) improves progression-free survival
compared with BR alone after a median followupof 12 months. This study (NCT01569295) was
unblinded by the independent data monitoring committee at first interim analysis for efficacy. We
now present updated data on overall survival (OS).

Methods: Between June 2012 and August 2014, 416 patients (pts) with RR CLL were enrolled in the
study across 19 countries. The current analysis data cutoff date of May 2016 represents a median
follow-up of 21 months. Progression-free survival based on independent review committee
assessment was the primary endpoint of this study, with OS as a secondary endpoint. All pts had
completed study treatment with BR. Key eligibility criteria included pts with RR CLL requiring therapy,
having received previous purine analog or bendamustine (ineligible if refractory to bendamustine);
and anti-CD20 antibody; relapsing or progressing within 36 months of the completion of the last
therapy. Patients were randomized to BR for 6 cycles Q 28 days (B = 70 mg/m2 D1, D2 of each cycle;
R = 375 mg/m2 C1 and 500 mg/m2 C2-6) and IDELA 150 mg BID or placebo (administered until
IRC-confirmed PD), death, intolerable toxicity, or withdrawal of consent. Stratification was based on
presence/absence of del(17p) and/or p53 mutation (mut), immunoglobulin heavy chain variable
region (IGHV) mutated/unmutated (analysis performed by a central lab), and disease status
refractory (CLL progression <6 months from completion of prior therapy) vs relapsed (CLL
progression 6 months from completion of prior therapy). Crossover was not permitted at the time
of PD or unblinding.

Results: The ITT population reflects 207/209 pts in the IDELA + BR/BR + placebo arm: 76% male;
42% 65 years; Rai stage III/IV 46%; median time since completion of last prior therapy 16 months;
pts with high-risk features (del[17p]/p53mut 32.9%, unmutated IGHV 83.2%, refractory 29.8%);
median number of prior therapies: 2 (range 113); and median follow-up 21 months. All pts have
completed study treatment with BR. A total of 65 pts remain on study treatment: 64 on IDELA
monotherapy and 1 pt on placebo. Overall by ITT and IRC, 260/416 pts (IDELA/placebo 95/165)
have met the primary endpoint of PD or death. Median OS (mo) of IDELA + BR vs BR + placebo was
not reached vs 41 (HR = 0.67; p value 0.036; 95% CI 0.47, 0.96) (Figure 1). The safety findings were
similar to what we previously reported: Serious AEs occurred in 147 (71%)/94 (5%) IDELA/placebo
arms, respectively. The commonly occurring SAEs by system organ class were infections and
infestations (41%/23%) and by MEDRA-preferred terms febrile neutropenia 43 (21%)/10 (5%) and
pneumonia 35 (17%)/16 (8%) in the IDELA/placebo arms respectively. The total number of pts with
opportunistic infections (Pneumocystis jirovecii pneumonia [PJP]/cytomegalovirus [CMV]) in the IDELA
arm was 5/13 vs 0/3 in the placebo arm.

Conclusion: IDELA in combination with BR is superior to BR alone with regard to OS in RR CLL. The
improvement in OS was observed across risk categories. Opportunistic infections (PJP, CMV) and
SAEs were more frequent in the IDELA vs placebo arm. Results of IDELA-containing regimens may be
further improved with implementation of adequate PJP prophylaxis and CMV monitoring measures.
This regimen represents an important new option for pts with RR CLL.
Figure 1: KaplanMeier Curve: Overall Survival.

Disclosures: Zelenetz: Adaptive Biotechnology: Membership on an entity's Board of Directors or

advisory committees; Bristol Myers: Research Funding; Portola Pharmaceuticals: Membership on an
entity's Board of Directors or advisory committees; Nanostring Tech: Membership on an entity's
Board of Directors or advisory committees; Novartis: Consultancy; Takeda Pharma: Consultancy,
Honoraria; Amgen: Consultancy; Hospira: Consultancy; Janssen: Consultancy, Research
Funding; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory
committees; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory
committees; GSK: Consultancy, Research Funding; Genentech/Roche: Consultancy, Membership on
an entity's Board of Directors or advisory committees; Boehringer Ingelheim: Other: DMC
Membership; Acerta Pharma: Consultancy; Cancer Genetics: Membership on an entity's Board of
Directors or advisory committees; Onyx: Membership on an entity's Board of Directors or advisory
committees; Parmacyclics: Consultancy; Roche: Membership on an entity's Board of Directors or
advisory committees, Research Funding; Sandoz: Consultancy. Brown: Celgene: Consultancy; Sun
BioPharma: Consultancy; Pfizer: Consultancy; Roche/Genentech: Consultancy; Gilead
Sciences: Consultancy; Janssen: Consultancy; Infinity: Consultancy; Abbvie: Consultancy. Delgado: Ro
che: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria; Gilead
Sciences: Consultancy,
Honoraria; GSK/Novartis: Honoraria; Abbvie: Consultancy. Eradat: Genentech: Consultancy,
Honoraria, Speakers Bureau; AbbVie: Consultancy, Honoraria, Research Funding, Speakers
Bureau; Gilead: Consultancy, Honoraria, Research Funding, Speakers
Bureau; Pharmacyclics: Consultancy, Honoraria. Ghia: Adaptive: Consultancy; Gilead: Consultancy,
Honoraria, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers
Bureau; Roche: Honoraria, Research Funding; Abbvie: Consultancy, Honoraria. Jurczak: Celltrion,
Inc: Research Funding; Acerta: Research Funding; Gilead Sciences: Research Funding; Bayer: Research
Funding; Janssen: Research Funding. Loscertales: Roche: Honoraria, Speakers
Bureau; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees,
Speakers Bureau; Gilead Sciences: Honoraria, Membership on an entity's Board of Directors or
advisory committees. MacDonald: Gilead Sciences: Speakers
Bureau. Morschhauser: Servier: Consultancy, Honoraria; Gilead Sciences: Consultancy,
Honoraria; Roche: Consultancy, Honoraria; Janssen: Honoraria; Celgene: Consultancy, Honoraria. De
la Serna: Abbvie: Consultancy; Roche: Consultancy, Speakers Bureau; Janssen: Consultancy, Speakers
Bureau; Gilead Sciences: Consultancy, Speakers Bureau. Shadman:Pharmacyclics: Honoraria, Research
Funding. Pocock: Gilead Sciences: Other: Sponsorship to attend the EHA 2016
Meeting; Janssen: Speakers Bureau; Takeda: Honoraria. Adewoye: Gilead Sciences: Employment,
Equity Ownership. Kim: Gilead Sciences: Employment, Equity
Ownership. Simpson: Celgene: Honoraria, Membership on an entity's Board of Directors or advisory
committees; Roche: Membership on an entity's Board of Directors or advisory
committees. Stilgenbauer: Boehringer Ingelheim: Consultancy, Honoraria, Other: Travel grants ,
Research Funding; Pharmacyclics: Consultancy, Honoraria, Other: Travel grants , Research
Funding; Novartis: Consultancy, Honoraria, Other: Travel grants , Research
Funding; AbbVie: Consultancy, Honoraria, Other: Travel grants, Research Funding; GSK: Consultancy,
Honoraria, Other: Travel grants , Research Funding; Mundipharma: Consultancy, Honoraria, Other:
Travel grants , Research Funding; Hoffmann-La Roche: Consultancy, Honoraria, Other: Travel grants
, Research Funding; Sanofi: Consultancy, Honoraria, Other: Travel grants , Research
Funding; Gilead: Consultancy, Honoraria, Other: Travel grants , Research
Funding; Janssen: Consultancy, Honoraria, Other: Travel grants , Research
Funding; Celgene: Consultancy, Honoraria, Other: Travel grants , Research
Funding; Genzyme: Consultancy, Honoraria, Other: Travel grants , Research
Funding; Genentech: Consultancy, Honoraria, Other: Travel grants , Research
Funding; Amgen: Consultancy, Honoraria, Other: Travel grants, Research Funding.

signifies non-member of ASH