1. Idelalisib: Analysis of Pivotal Data
Jeff Sharman M.D.
Willamette Valley Cancer Institute Eugene Oregon
US Oncology Research

2. Disclosures Consulting: Gilead, Pharmacyclics, Celgene
Research Funding: Gilead, Pharmacyclics, Genentech, Seattle Genetics, Celgene, Novartis, TG Therapeutics
Honoraria: Gilead, Genentech

3. US Labeled Indications
Indications referenced from:

4. Monotherapy Publications
Strategy
ORR
PFS
Byrd JCO 2001
Intensification
3x weekly
45%
10 Months
O’Brien JCO 2001
Escalation
mg/m2
36%
8 Months

5. Patterns of Care First Line Therapy Second Line Therapy Connect
US Oncology
FCR/PCR 32 17 18 4
R-Benda 27 33 38 43
Rituximab 14 21 24
Flu +/- Ritux 10 5 13 -
Chlorambucil 7 3
Sharman et al ASH 2011
Market Connect / McKesson Specialty Health

6. Single agent idelalisib 101-02 Study
Brown et al Blood 2014

7. Single agent idelalisib 101-02 Study
Brown et al Blood 2014

8. Idelalisib Combination 101-07 Study
Sharman et al ASH 2011

9. Idelalisib Combination 101-07 Study
Sharman et al ASH 2011

10. CLL Registration Study

11. Study Context Full Development Early Development 2011-2016 iNHL
Accelerated Approval
Refractory iNHL
Phase 2 single-agent ( Study)
Early Development
Previously treated CLL Phase 3 combination with CD-20 mAb
116/117 Study: R ± GS-1101
119 Study: Ofa ± GS-1101
CLL
Full Approval
Previously treated CLL Phase 3 combination with chemoimmunotherapy
115 Study: BR ± GS-1101
Healthy Volunteer Trials
Dose-ranging
Metabolism
Hematologic Cancer Trials
Single-agent ( Study)
Combination ( Study)
Combination ( Study)
Previously treated iNHL
Phase 3 combination immuno or chemoimmunotherapy
124 Study: R ± GS-1101
125 Study: BR ± GS-1101
iNHL
Full Approval
Exploration & Indication Expansion
Additional studies – lymphoid malignancies 11 11 11

13. “…in patients for whom rituximab alone would be considered appropriate therapy due to other comorbidities”
Characteristic
Percentage
Median
Age > 65
78% 71
Cr Clearance < 60
40%
64 ml/min
Grade 3 Marrow
35%
CIRS > 6
85% 8

14. Treatment Disposition
Coutre et al ASCO 2014

16. Outcomes
Coutre et al ASCO 2014

17. Black Box - Grade 5 Toxicity
Hepatotoxicity
1/1192 = 0.1%
Diarrhea
1/1192 = <0.1%
Pneumonitis
3/760 = 0.5%
Perforation
2/1192 = 0.2%
Referenced from:

18. Coutre et al ASCO 2014

19. Coutre et al ASCO 2014

20. 17P / 11Q
Study arm +/- 17P
Study arm +/- 11Q
Sharman et al ASCO 2014

21. Frontline Idelalisib + Rituximab
O’Brien et al ASCO 2013

22. European Indications
Indications referenced from:

23. Therapeutic Selection
Idelalisib with rituximab
Ibrutinib
Any patient receiving rituximab
On blood thinners
Atrial fibrillation
Renal insufficiency
17P?
Abnormal liver function
History of bowel difficulties
Lung issues
Monotherapy preferred

24. Thank You