2015 Oncology Annual Meeting in Chicago. prime Downloadable Slides in Chronic Lymphocytic Leukemia and Indolent Non-Hodgkin Lymphoma.

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1 2015 Oncology Annual Meeting in Chicago prime Downloadable Slides in Chronic Lymphocytic Leukemia and Indolent Non-Hodgkin Lymphoma May 29-June 2

2 Ibrutinib Combined With Bendamustine and Rituximab in Previously Treated CLL/SLL: First Results From a Randomized, Double-Blind, Placebo- Controlled, Phase 3 Study Abstract #LBA7005 Chanan-Khan, A, Cramer P, Demirkan F, Fraser G, Silva RS, Pylypenko H, Grosicki S, Janssens A, Pristupa A, Mayer J, Dilhuydy MS, Loscertales J, Bartlett N, Avigdor A, Rule S, Sun S, Mahler M, Salman M, Howes A, Hallek M

3 Introduction CLL/SLL remains incurable, thus the goal of post-relapse therapy is to control the disease and provide long, durable remission Ibrutinib is a first-in-class, once-daily, oral covalent inhibitor of BTK, which improved PFS and OS versus ofatumumab in previously treated CLL/SLL in the phase 3 RESONATE study 1 Ibrutinib is now recommended by the NCCN (Category 1) as the preferred agent in the CLL/SLL relapsed setting BR is used in the first line and relapsed setting 2,3,4 A phase 1b study of ibrutinib in combination with BR in CLL patients showed an ORR of 93.3% and a PFS rate of 70.3% at 36 months 5 In the phase 3 HELIOS trial, we examined ibrutinib versus placebo in combination with BR 1. Byrd JC, et al. N Engl J Med. 2014;371: NCCN Clinical Practice Guidelines in Oncology-Non-Hodgkin s Lymphomas. Version Eichhorst B, et al. Ann Oncol. 2011;22:vi50-vi Eichhorst B, et al. Blood. 2014;124: Brown JR, et al. Blood. 2015;125: Chanan-Khan A, et al. J Clin Oncol. 2015;33(suppl): Abstract LBA7005.

4 HELIOS: Phase III Study Design Patients with previously treated CLL/SLL R A N D O M I Z E 1:1 * Ibrutinib + BR (N = 289) BR (maximum of 6 cycles) Oral ibrutinib 420 mg once daily starting on Cycle 1, Day 2 Placebo + BR (N = 289) BR (maximum of 6 cycles) Oral placebo once daily starting on Cycle 1, Day 2 Ibrutinib (treat to PD or unacceptable toxicity Placebo (treat to PD or unacceptable toxicity Enrollment Dates: Sept 2012 Jan 2014 Crossover to ibrutinib 420 mg once daily after IRC-confirmed PD (n = 90) First patient crossed over in May 2014 IRC, independent review committee; PD, progression of disease * Stratified by disease refractory to purine analog chemoimmunotherapy (failure to respond or relapse within 12 months) and the number of prior lines of therapy (1 line vs > line) BR (similar to Fischer K, et al. J Clin Oncol. 2011; 29: ): bendamustine: 70 mg/m 2 IV on Cycle 1, Days 2-3 and Cycles 2-6, days 1-2; rituximab: 375 mg/m 2 on Cycle 1, Day 1, and 500 mg/m 2 on Cycles 2-6, Day 1. Chanan-Khan A, et al. J Clin Oncol. 2015;33(suppl): Abstract LBA7005.

5 Study Endpoints Primary end point IRC-assessed PFS * Secondary end points IRC-assessed ORR confirmed by at least 2 CT scans performed every 12 weeks, per protocol OS Rate of MRD-negative response Safety CT, computerized tomography; MRD, minimal residual disease *According to 2008 iwcll criteria (Hallek M, et al. Blood. 2008;111: ) Central laboratory assessment of peripheral blood or bone marrow aspirate Chanan-Khan A, et al. J Clin Oncol. 2015;33(suppl): Abstract LBA7005.

6 Key Eligibility Criteria Active CLL/SLL requiring treatment according to 1 iwcll criteria and age 18 years 1 Relapsed or refractory CLL/SLL following 1 prior line of systemic therapy (min. 2 cycles) ECOG PS of 0-1 Measurable lymph node disease (>1.5 cm) by CT scan Adequate bone marrow, liver, and kidney functions No del17p (defined as the presence of del17p in 20% of cells examined by FISH) ECOG PS, Eastern Cooperative Oncology Group performance score; FISH, fluorescence in situ hybridization 1. Hallek M, et al. Blood. 2008;111: Chanan-Khan A, et al. J Clin Oncol. 2015;33(suppl): Abstract LBA7005.

7 Baseline Characteristics ITT population Ibrutinib + BR (N = 289) Placebo + BR (N = 289) Median age (range), years 64 (31-86) 63 (36-83) Male, n (%) 193 (66.8) 189 (65.4) CLL, n (%) 257 (88.9) 257 (88.9) SLL, n (%) 32 (11.1) 32 (11.1) ECOG PS, n (%) (43.3) 126 (43.6) (56.7) 163 (56.4) Rai stage, * n (%) 0-II 157 (61.3) 139 (53.9) III-IV 99 (38.7) 119 (46.1) Bulky disease > 5 cm, n (%) 168 (58.1) 156 (54.0) Del11q, n (%) 87 (30.1) 65 (22.5) IgVH status, n (%) Mutated 49 (18.9) 52 (20.0) Unmutated 210 (81.1) 208 (80.0) * Ibrutinib + BR (n = 256)/placebo + BR (n = 258) Ibrutinib + BR (n = 259)/placebo + BR (n = 260) Chanan-Khan A, et al. J Clin Oncol. 2015;33(suppl): Abstract LBA7005.

8 Drug Exposure Safety population Ibrutinib + BR (N = 287) Placebo + BR (N = 287) BR Received 6 cycles of Br, n (%) 235 (81.9) 222 (77.4) Ibrutinib/placebo Median dose intensity, % Median study drug exposure (range), months 14.7 ( ) 12.8 ( ) 12 months exposure, n (%) 210 (73.2) 160 (55.7) Chanan-Khan A, et al. J Clin Oncol. 2015;33(suppl): Abstract LBA7005.

9 Patient Disposition ITT population Ibrutinib + BR (N = 289) Placebo + BR (N = 289) Treatment phase disposition, n (%) Did not receive study drug 2 (0.7) 2 (0.7) Ongoing 203 (70.2) 100 (34.6) Discontinued 84 (29.1) 187 (64.7) Primary reason for discontinuation, * n (%) Progressive disease or relapse 14 (4.8) 130 (45.0) AE 41 (14.2) 34 (11.8) Withdrawal of consent 17 (5.9) 12 (4.2) Death 9 (3.1) 8 (2.8) Investigator decision 4 (1.4) 4 (1.4) Lost to follow-up 1 (0.3) 1 (0.3) AE, adverse event; ITT, intent-to-treat. * Includes patients who did not receive study drug Chanan-Khan A, et al. J Clin Oncol. 2015;33(suppl): Abstract LBA7005.

10 Primary Endpoint: IRC-Assessed PFS * Investigator-assessed HR for ibrutinib + BR vs placebo + BR was (95% CI: ) No Richter s transformations were observed on the ibrutinib arm and 3 on the placebo arm Chanan-Khan A, et al. J Clin Oncol. 2015;33(suppl): Abstract LBA7005.

11 IRC-Assessed PFS * : Subgroup Analysis Group/Subgroup Parameter N HR (95% CI) All Patients (0.15, 0.28) Age (years) < (0.11, 0.26) > (0.18, 0.42) Sex Male (0.14, 0.28) Female (0.13, 0.39) Diagnosis CLL (0.14, 0.27) SLL (0.19, 0.85) Rai stage at screening Stage 0-II (0.08, 0.21) Stage III-IV (0.19, 0.48) Refractory to purine analog therapy Yes (0.14, 0.39) No (0.13, 0.28) Prior lines of therapy (0.12, 0.31) > (0.15, 0.33) Baseline ECOG (0.09, 0.26) (0.18, 0.38) Bulky disease No (<5 cm) (0.13, 0.37) Yes (> 5 cm) (0.13, 0.27) Del11q Yes (0.04, 0.16) No (0.19, 0.39) IgVH Mutated (0.19, 0.97) Unmutated (0.11, 0.23) Favors Ibrutinib + BR Favors Placebo + BR ITT population; the All Patients HR is from a stratified proportional hazards model. HRs for subgroups are unstratifed. HR= Hazard Ratio. Chanan-Khan A, et al. J Clin Oncol. 2015;33(suppl): Abstract LBA7005.

12 100 ORR * : IRC and Investigator Assessment IRC assessment ORR: 82.7% vs 67.8% (P<.0001) 100 Investigator assessment ORR: 86.2% vs 68.9% (P<.0001) % % % 60 } 2.8% % % % % % 0 CR CRi PR 8.7% 0.7% 0.3% 2.1% 0.3% 1.0% 2.4% 0 0.0% I PR+L I I I CR I I I SD PD PR+L SD PD CR I I I I PR+L CR I I I CRi SD PD PR+L SD PD Cri Cri PR PR PR Ibrutinib + BR (N=289) Placebo + BR (N=289) Ibrutinib + BR (N=289) Placebo + BR (N=289) 7.6% * ORR = CR + CRi + npr + PR Chanan-Khan A, et al. J Clin Oncol. 2015;33(suppl): Abstract LBA7005.

13 Overall Survival * Chanan-Khan A, et al. J Clin Oncol. 2015;33(suppl): Abstract LBA7005.

14 Rate of CR/CRi (%) MRD Negativity Ibrutinib + BR Placebo + BR ITT population (N = 289) (N = 289) P value MRD ve response *, n (%) 37 (12.8) 14 (4.8).0011 *MRD ve status, < 1 CLL cell/10,000 leukocytes; 120 and 57 patients had MRD assessed in the ibrutinib + BR and placebo + BR arms, respectively MRD ve in CR/Cri responders IRC assessment Not MRD -ve MRD -ve % Investigator assessment % Ibrutinib + BR I 2.8% 1.4 Placebo + BR Ibrutinib + BR 5.9% 2.4 Placebo + BR *Includes patients with missing MRD data Chanan-Khan A, et al. J Clin Oncol. 2015;33(suppl): Abstract LBA7005.

15 Treatment-Emergent AEs (>15% of Patients) Safety population Ibrutinib + BR (N = 287) Placebo + BR (N = 287) AE, % Any Grade Grade ¾ Any Grade Grade ¾ Neutropenia Nausea Diarrhea Thrombocytopenia Pyrexia Anemia Fatigue Cough Constipation Rash Infusion-related reaction Upper respiratory infection Headache Vomiting Chanan-Khan A, et al. J Clin Oncol. 2015;33(suppl): Abstract LBA7005.

16 Infections, % Bleeding, % Major hemorrhage, * % Atrial fibrillation (AF), % Other Safety Observations Safety population All grades Ibrutinib + BR Placebo + BR (N = 287) 70.7 (N = 287) 70.0 Grade > All grades Grade 1/2 bleeding events, % Hematoma Contusion Epistaxis Ecchymosis Petechiae All grades Grades 3/ Tumor lysis syndrome, % Grade 3/ Of patients with a prior history of AF atrial flutter, 7/25 (28.0%) on ibrutinib + BR and 2/22 (9.1%) on placebo + BR, had an episode of AF/atrial flutter on study Rates of other malignancies during treatment and follow-up were similar (8.4% ibrutinib + BR vs 8.0% placebo + BR) * Major hemorrhage includes grade > 3 hemorrhage, central nervous system hemorrhage, and serious bleeding events of any grade. Most patients with grade 3/4 AF had a history of AF or other relevant risk factors. Not fatal events occurred. Chanan-Khan A, et al. J Clin Oncol. 2015;33(suppl): Abstract LBA7005.

17 Conclusions Ibrutinib + BR compared with placebo + BR: Significantly reduced the risk of progression or death by 80% Significantly improved the ORR The safety profile of ibrutinib + BR was consistent with the known individual safety profiles These results demonstrate that ibrutinib + BR is superior to a current standard of care with BR in previously treated patients with CLL/SLL HELIOS is the second randomized phase 3 study demonstrating that ibrutinib significantly delays relapse for patients with previously treated CLL/SLL Chanan-Khan A, et al. J Clin Oncol. 2015;33(suppl): Abstract LBA7005.

18 GADOLIN: Primary Results from a Phase 3 Study of Obinutuzumab Plus Bendamustine Compared with Bendamustine Alone in Patients with Rituximab-Refractory Indolent Non- Hodgkin Lymphoma Abstract #LBA8502 Sehn LH, Chua N, Mayer J, Dueck G, Trneny M, Bouabdallah K, Fowler N, Delwail V, Press O, Salles G, Gribben J, Lennard A, Lugtenberg PJ, Franklin N, Wassner-Fritsch E, Fingerle-Rowson G, Cheson BD

19 Introduction Despite an increase in the number of chemotherapeutic options, advanced stage indolent NHL remains incurable Addition of rituximab to chemotherapy during induction followed by maintenance has significantly improved outcomes in patients with indolent NHL Patients with disease which is refractory to a rituximab-containing therapy have limited treatment options Bendamustine was shown to be effective in this patient population (75% to 77% ORR), but median PFS was short (7-9 months) 1,2 The GADOLIN study was designed to evaluate whether the combination of obinutuzumab, a novel anti-cd20 monoclonal antibody, with bendamustine followed by obinutuzumab maintenance could improve outcome in patients with rituximab-refractory indolent NHL 1. Friedberg JW, et al. J Clin Oncol. 2008;26(2): Kahl BS, et al. Cancer. 2010;116(1): Sehn LH, et al. J Clin Oncol. 2015;33(suppl): Abstract LBA8502.

20 Obinutuzumab in NHL Obinutuzumab (GA101[G]), is a glycoengineered type II anti- CD20 monoclonal antibody 1-4 with activity and acceptable safety in phase 1 studies in relapsed/refractory NHL 5,6 Obinutuzumab plus bendamustine achieved superior tumor growth inhibition versus rituximab plus bendamustine in xenograft models of human lymphoma 7 Increased direct cell death and lower complement activation than type I antibodies 1 Glycoengineered to have increased affinity to FcγRIIIa/b and enhanced antibody-dependent cytotoxicity (ADCC) and phagocytosis (ADCP) vs type I antibodies 1,2 1. Mössner E, et al. Blood. 2010;115(22): Golay J, et al. Blood. 2013;122(20): Niederfellner G, et al. Blood. 2011;118(2): Ferrara C, et al. Proc Natl Acad Sci U S A. 2011;108(31): Sehn LH, et al. Blood. 2012;119(22): Salles G, et al. Blood. 2012;119(22): Herting F, et al. Leuk Lymphoma. 2014;55(9): Sehn LH, et al. J Clin Oncol. 2015;33(suppl): Abstract LBA8502.

21 GADOLIN: Study Design (NCT ) Rituximab-refractory CD20+ inhl (incl FL, MZL, and SLL) (n = 413) R 1:1 Stratification factors: NHL subtype (FL vs other) Prior therapies ( 2 vs >2) Refractory type R-mono vs R-chemo) Geographic region G-B B CR/PR/SD Obinutuzumab 1000 mg IV days 1, 8, and 15 cycle 1; Day 1 cycle 2-6 (28-day cycles) Bendamustine 90 mg/m 2/ day IV days 1 and 2 cycles 1-6 (28-day cycles) Bendamustine 120 mg/m 2 /day IV days 1 and 2 cycles 1-6 (28-day cycles) G Maintenance Obinutuzumab 1000 mg IV every 2 months for 2 years or until progression International, randomized, open-label study Response monitored by CT scan post-induction, then every 3 months for 2 years, then every 6 months G-B, obinutuzumab plus bendamustine; G, obinutuzumab Sehn LH, et al. J Clin Oncol. 2015;33(suppl): Abstract LBA8502.

22 GADOLIN: Study Endpoints Primary endpoint: PFS as assessed by an independent radiology facility (IRF) Secondary endpoints: PFS as assessed by investigator, OS End of induction response Best overall response Duration of response, EFS, DFS Safety Pharmacokinetic profile Pharmacoeconomics Patient-reported outcomes (PROs) Statistical assumptions 410 patients/260 events required for an 80% power to detect a hazard ratio of G-B vs B of 0.70 (43% improvement in median PFS from 9.3 months to 13.3 months), with a twosided log-rank test α of 0.05 Interim efficacy analysis planned once 170 (65%) PFS events observed Based on IDMC recommendation, the study is reported at the planned interim efficacy analysis because the primary endpoint was met Sehn LH, et al. J Clin Oncol. 2015;33(suppl): Abstract LBA8502.

23 GADOLIN: Patient Selection and Definition of Rituximab-Refractory Patients had rituximab-refractory CD20+ inhl (including FL, MZL, and SLL) No exposure to bendamustine in the last 2 years No exposure to mabs (except rituximab) in the last 3 months or any exposure to obinutuzumab Patients were considered rituximab-refractory if they: Did not respond to either rituximab monotherapy or rituximab in combination with chemotherapy or Progressed within 6 months of completion of the last dose of a rituximab-containing regimen - After at least 4 doses of rituximab monotherapy or 4 cycles of rituximab + chemotherapy Sehn LH, et al. J Clin Oncol. 2015;33(suppl): Abstract LBA8502.

24 GADOLIN: Patient Disposition 32 (16.5%) withdrew* AE, n = 15; PD, n = 9 Subject decision, n = 4 Physician decision, n = 5 Death, n = 2 13 (8.3%) did not start maintenance AE, n = 3; PD, n = 6 Physician decision, n = 1 Started after cut-off, n = 3 62 (43.4%) withdrew* AE, n = 18 PD, n = 44 Subject decision, n = 3 Physician decision, n = 2 Death, n = 2; Other, n = 2 G-B, n = 194 G-B, n = still on G-B G-B, n = 156 G-B, n = still on G G-B, n = 35** Enrolled and randomized Started induction Completed induction Started maintenance Completed maintenance B, n = 202 B, n = 198 B, n = still on B 4 (2.0%) received no treatment 58 (27.7%) withdrew AE, n = 30 PD, n = 14 Subject decision, n = 7 Physician decision, n = 2 Death, n = 2; Other, n = 1 *Withdrawal of both drugs. Eleven additional patients stopped one drug (B, n = 10; G, n = 1) **One additional patient received all G maintenance, but was considered withdrawn due to PD; overall, 36 patients were recorded as having received all 12 doses Data analysis cut-off: September 1, 2014 Median follow-up was 21 months Patients still on study: G-B, n = 149; B, n = 141 Sehn LH, et al. J Clin Oncol. 2015;33(suppl): Abstract LBA8502.

25 GADOLIN: Patient Characteristics Characteristic G-B (n = 194) B (n = 202) Median age, years (range) 63 (34-87) 63 (21-87) Male, n (%) 110 (57) 118 (58) FLIPI at initial diagnoses, n/patients with data (%) Low (0-1) 42/155 (27) 34/165 (21) Intermediate (2) 47 /155 (30) 58/165 (35) High ( 3) 60 /155 (39) 67/165 (41) Unknown 6/155 (4) 6/165 (4) β2 microglobulin at diagnosis, n/patients with data (%) <3.5 mg/l 145/185 (78) 136/183 (74) 3.5 mg/l 40/185 (22) 47/183 (26) Bone marrow involvement at enrollment, n/patients with data (%) 60/187 (32) 69/188 (37) Extranodal involvement at enrollment, n/patients with data (%) 107/194 (55) 98/201 (49) Bulky disease (>6 cm) at enrollment, n/patients with data (%) 66/194 (34) 70/199 (35) Sehn LH, et al. J Clin Oncol. 2015;33(suppl): Abstract LBA8502.

26 GADOLIN: Baseline Characteristics Characteristic G-B (n = 194) B (n = 202) Mean time from diagnosis to randomization, years (range) 4.2 (0.3-32) 4.2 (0.3-30) Median prior lines of therapy, n (range) 2 (1-10) 2 (1-7) Median time since last dose of last prior regimen, months (maximum) 4.0 (128.4) 3.7 (64.0) Number of patients refractory to last treatment, n (%) 178 (92) 187 (93) Patients double refractory to rituximab and alkylators, n (%)* 147 (76) 164 (81) *Double refractory to rituximab and an alkylating agent from same or different regimens Sehn LH, et al. J Clin Oncol. 2015;33(suppl):Abstract LBA8502.

27 GADOLIN: Baseline Disease Characteristics Lymphoma Subtype Rituximab-Refractory Type G-B (n = 194) B (n=202) 0.5 WM SLL MZL FL G-B (n = 194) B (n = 202) R-monotherapy R-chemotherapy combination* *Including patients who relapsed during or within 6 months of R-maintenance following R-chemotherapy FL, follicular lymphoma; MZL, marginal zone lymphoma, including extranodal, nodal, and splenic; SLL, small lymphocytic lymphoma; WM, Waldenström macroglobulinemia Sehn LH, et al. J Clin Oncol. 2015;33(suppl): Abstract LBA8502.

28 GADOLIN: Study Drug Exposure Induction Therapy G 1000 mg x 8 (n = 194) G-B B 90 mg/m 2 x mg/m 2 x 12 (n = 193) (n = 198) All scheduled doses received, n (%) 145 (75) 137 (71) 123 (62) Mean no. of doses received (SD) 7.2 (1.74) 10.5 (2.93) 10.2 (2.92) Patients with 1 dose reduction* NA 34 (18) 54 (27) Median cumulative dose, mg/m 2 (range)** NA 1071 ( ) 1327 ( ) Patients with 90% dose intensity*** 175 (90) 154 (80) 153 (77) B Maintenance Therapy G 1000 mg q2 months (n = 143) All 12 maintenance doses received, n (%) 36 (25) Patients still receiving maintenance, n (%) 46 (32) Median duration of exposure, months (range) 10.8 ( ) * B dose reduction of 25% (B-arm) of 33% (G-B arm) ** Based on calculated BSA at baseline *** Percentage of planned dose based on dose at C1D1 for cycles received Sehn LH, et al. J Clin Oncol. 2015;33(suppl): Abstract LBA8502.

29 Patients, % GADOLIN: Overview of AEs AEs 1 SAEs 1 AEs leading to withdrawal of any treatment AEs leading to dose modification grade 3-4 AEs G-B (n = 194) B (n =198) AE leading to death Sehn LH, et al. J Clin Oncol. 2015;33(suppl): Abstract LBA8502.

30 GADOLIN: Adverse Events Grade 3-4 AE, n (%)* Hematologic AEs G-B (n = 194) B (n = 198) Neutropenia 64 (33.0) 52 (26.3) Thrombocytopenia 21 (10.8) 32 (16.2) Anemia 15 (7.7) 20 (10.1) Febrile neutropenia 9 (4.6) 7 (3.5) Leukopenia 2 (1.0) 3 (1.5) * Multiple occurrences of the same AE in an individual were counted once Nonhematologic AEs** G-B B AE, n (%)* (n = 194) (n = 198) IRR*** 21 (10.8) 11 (5.6) Vomiting 4 (2.1) 2 (1.0) Decreased appetite 3 (1.5) 2 (1.0) Fatigue 3 (1.5) 5 (2.5) Nausea 2 (1.0) 6 (3.0) Diarrhea 2 (1.0) 5 (2.5) Pyrexia 2 (1.0) 0 Headache 1 (0.5) 2 (1.0) * Multiple occurrences of the same AE in an individual were counted once ** AEs with 15% incidence across all grades *** AEs occurring within 24 hours after an infusion and considered to be related to the study drug IRR, infusion-related reaction Sehn LH, et al. J Clin Oncol. 2015;33(suppl): Abstract LBA8502.

31 GADOLIN: Serious Adverse Events AE, n (%)* Hematologic SAEs G-B (n = 194) B (n = 198) Febrile neutropenia 8 (4.1) 6 (3.0) Neutropenia 6 (3.1) 1 (0.5) Thrombocytopenia 4 (2.1) 0 Anemia 3 (1.5) 3 (1.5) Leukopenia 0 1 (0.5) * Multiple occurrences of the same SAE in an individual were counted once AE, n (%)* Nonhematologic SAEs** G-B (n = 194) B (n = 198) IRR*** 8 (4.1) 3 (1.5) Sepsis 6 (3.1) 7 (3.5) Pneumonia 5 (2.6) 10 (5.1) Pyrexia 5 (2.6) 3 (1.5) * Multiple occurrences of the same SAE in an individual were counted once ** SAEs with 2.5% incidence *** SAEs occurring within 24 hours after an infusion and considered to be related to the study drug Sehn LH, et al. J Clin Oncol. 2015;33(suppl): Abstract LBA8502.

32 Patients, % GADOLIN: Response to Therapy End-of-Induction Response (IRF) Best Overall Response to 12 Months (IRF) CR PR SD G-B (n = 188)* B (n = 189)* G-B (n=188)* B (n=189)* PD NE/missing 19 patients still in induction (G-B, n=6; B, n=13) * Patients ongoing in induction therapy are excluded from analysis. Patients with end of induction response assessment performed >60 days after last induction dose shown as missing ** Best overall response excludes ongoing patients who have not yet reached the first response assessment IRF, independent radiology facility Sehn LH, et al. J Clin Oncol. 2015;33(suppl): Abstract LBA8502.

33 GADOLIN Primary Outcome: IRF-Assessed PFS IRF, independent radiology facility; HR, hazard ratio; CI, confidence interval; NR, not reached Sehn LH, et al. J Clin Oncol. 2015;33(suppl): Abstract LBA8502.

34 GADOLIN: Investigator-Assessed PFS Sehn LH, et al. J Clin Oncol. 2015;33(suppl): Abstract LBA8502.

35 GADOLIN: PFS by Sub-Group Subgroup Total G-B (n = 194) B (n = 202) Hazard ratio Event n Events n s (95% CI) Follicular lymphoma Yes ( ) No ( ) No. of prior therapies ( ) > ( ) Refractory type Rituximab + chemotherapy ( ) Rituximab monotherapy ( ) Sex Male ( ) Female ( ) Bulky disease at baseline Yes (>6 cm) ( ) No ( 6 cm) ( ) B symptoms at baseline Yes ( ) No ( ) Double refractory status Yes ( ) No ( ) Sehn LH, et al. J Clin Oncol. 2015;33(suppl): Abstract LBA8502.

36 GADOLIN: Overall Survival Sehn LH, et al. J Clin Oncol. 2015;33(suppl): Abstract LBA8502.

37 Summary Obinutuzumab plus bendamustine followed by obinutuzumab maintenance resulted in a statistically significant and clinically meaningful PFS benefit compared with bendamustine monotherapy IRF-assessed median PFS: not reached in G-B arm vs 14.9 months in B arm (HR = 0.55) No difference in response rates between treatment arms Bendamustine dose was higher in the B monotherapy arm No new safety signals were observed Obinutuzumab plus bendamustine followed by obinutuzumab maintenance represents an effect treatment options for patients with relapsed/refractory inhl who are refractory to rituximab Sehn LH, et al. J Clin Oncol. 2015;33(suppl): Abstract LBA8502.

38 Results of a Phase 3 Randomized, Controlled Study Evaluating the Efficacy and Safety of Idelalisib (IDELA) in Combination With Ofatumumab (OFA) for Previously Treated Chronic Lymphocytic Leukemia (CLL) Abstract #7023 Jones J, Wach M, Robak T, Brown JR, Menter AR, Vandenberghe E, Ysebaert L, Wagner-Johnson N, Polikoff J, Salman H, Taylor K, Coutre S, Spurgeon S, Kendall S, Flinn I, Dreiling L, Cho Y, Peterman S, Dubowy R, Owen C

39 Introduction Chronic lymphocytic leukemia Most common type of leukemia in adults in Western countries Progression following initial chemo-immunotherapy is common Older patients less able to tolerate cytotoxic chemotherapy Idelalisib (IDELA): FDA approved in combination with rituximab for previously treated patients with CLL for whom rituximab monotherapy is appropriate 1 Ofatumumab (OFA): FDA approved for previously treated patients with CLL refractory to fludarabine and alemtuzumab 1 Furman RR, et al. N Engl J Med. 2014;370(11): Jones J, et al. J Clin Oncol. 2015;33(suppl): Abstract 7023.

40 Idelalisib Targeted, highly selective, oral inhibitor of phosphatidylinositol 3 - kinase (PI3K)-δ Inhibits proliferation and induces apoptosis in many B-cell malignancies Inhibits homing and retention of malignant B cells in lymphoid tissues Jones J, et al. J Clin Oncol. 2015;33(suppl): Abstract 7023.

41 Objectives Primary: To evaluate the effect of the addition of IDELA to OFA on progression-free survival (PFS) in patients with previously treated CLL Secondary: To evaluate the effect of the addition of IDELA to OFA on overall response rate (ORR), lymph-node response rate (LNR), overall survival (OS), PFS in patients with del (17p)/TP53 mutation, and complete response (CR) rate Jones J, et al. J Clin Oncol. 2015;33(suppl): Abstract 7023.

42 Randomized 2:1 Study Design End of Study Disease progression Death from any cause Idelalisib (150 mg BID) Fit or unfit relapsed CLL Arm A n = 174 Arm B n = 87 Ofatumumab 1000 mg x 12 doses Ofatumumab 2000 mg x 12 doses Observation Long-term Follow-up for overall survival Jones J, et al. J Clin Oncol. 2015;33(suppl): Abstract 7023.

43 Methods Open-label study (NCT ) OFA dose and schedule 300 mg Week 1; then 1000 mg (Arm A) or 2000 mg (Arm B) weekly x 7 and then every 4 weeks x 4 (total 12 doses; finishing Week 24) First dose (300 mg) given minutes after IDELA dose Endpoints Primary: PFS Secondary: ORR, LNR, CR rate, OS, del(17p)/tp53mut (hierarchical testing strategy) Assumptions PFS control 8 months; experimental 14 months (hazard ratio [HR] = 0.57) Primary analysis at 129 PFS events Patients remain on study until disease progression even if all treatment has stopped Jones J, et al. J Clin Oncol. 2015;33(suppl): Abstract 7023.

44 Methods Cytogenetic and genetic* Clinical Stratification by 3 factors 17p deletion and/or TP53 mutation: Either vs neither IGHV mutation: mutated vs unmutated Recurrent disease status: refractory vs relapsed *Samples analyzed by Cancer Genetics, Inc., Rutherford, NJ. First evidence of CLL progression <6 months from completing last therapy. IGHV, immunoglobulin heavy chain variable region gene. Jones J, et al. J Clin Oncol. 2015;33(suppl): Abstract 7023.

45 Key Eligibility Criteria Inclusion Diagnosis of B-cell CLL and requiring treatment, per International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria 1 CLL progression <24 months from completion of last therapy Prior therapy: 2 cycles of a purine analog or bendamustine Karnofsky score 60 Complete blood count: any values Estimated creatinine clearance (ecrcl) >30mL/min (Cockcroft-Gault) Exclusion Prior therapy with inhibitor of AKT, BTK, JAK, mtor, PI3K, or SYK Prior allogeneic stem cell or solid organ transplantation Progression within 6 months of last OFA dose 1 Hallek M, et al. Blood. 2008;111(12): Jones J, et al. J Clin Oncol. 2015;33(suppl): Abstract 7023.

46 Assessments Disease status assessments per modified IWCLL , 2 CT or MRI scans required at baseline, weeks 8, 16, and 24, and every 12 weeks thereafter Response assessed by independent review committee based on imaging, clinical,and laboratory data 1 Hallek M, et al. Blood. 2008;111(12): Cheson BD, et al. J Clin Oncol. 2012;30(23): Jones J, et al. J Clin Oncol. 2015;33(suppl): Abstract 7023.

47 Baseline Patient Characteristics IDELA + OFA, n = 174 OFA, n = 87 Total, n = 261 Male, % Age, years, median (range) 68 (40,85) 67 (36, 84) 68 (36, 85) Time since diagnosis, year, median (range) 7.8 (0.7, 29.3) 7.6 (0.6, 22.4) 7.7 (0.6, 29.3) Rai Stage at screening, II/ III / IV, % 15/ 14 / 53 24/ 12 / 45 18/ 13 / 51 Binet stage at screening, B/C, % 29/ 62 33/ 52 31/ 58 CIRS score, median [Q1, Q3] 4 [2,7] 4 [2,7] 4 [2,7] Karnofsky score, median [Q1, Q3] 80 [80, 90] 80 [80, 90] 80 [80, 90] ecrcl, ml/min, median [Q1, Q3] 71.4 [56.4, 88.8] 75.0 [56.4, 99.6] 73.2 [56.4, 91.8] Β2 microglobulin, mg/l, median [Q1, Q3] 6.1 [3.9, 8.1] 5.3 [4.2, 7.4] 5.6 [4.0, 7.8] Bulky disease, % >1 5-cm lymph node >1 10-cm lymph node Refractory disease, % Hepatomegaly / splenomegaly, % 52/ 75 56/ 70 53/ 74 17p deletion and/or TP53 mutation, % IGHV unmutated, % CIRS, cumulative illness rating scale; ecrcl, Cockcroft-Gault estimated creatinine clearance. Q, quartile Jones J, et al. J Clin Oncol. 2015;33(suppl): Abstract 7023.

48 Prior Therapy IDELA + OFA, n = 174 OFA, n = 87 Total, n = 261 Time since last therapy, months, median [Q1, Q2] 9.3 [5.1, 20.3] 9.3 [3.6, 17.9] 9.3 [4.3, 19.4] Number of prior regimens, median (range) 3 (1, 11) 3 (1, 11) 3 (1, 11) Most common last regimen at study entry, % BR FCR FR Rituximab Prior exposure at any time, % Rituximab Fludarabine Cyclophosphamide Bendamustine Chlorambucil Ofatumumab B, bendamustine; C, cyclophosphamide; F, fludarabine; R, rituximab Jones J, et al. J Clin Oncol. 2015;33(suppl): Abstract 7023.

49 Patient Disposition and Treatment Exposure IDELA + OFA, n = 174 OFA, n = 87 Total, n = 261 Randomized, n Treated with study drug, n Ongoing, n (%) 84 (48) 6 (7) 90 (35) Met primary endpoints, n (%)* Disease progression 34 (20) 41 (47) 75 (29) Death 22 (13) 6 (7) 28 (11) Early discontinuation from study, n (%) 34 (20) 34 (39) 68 (26) AE 2 (1) 3 (3) 5 (2) Withdrew consent 12 (7) 14 (16) 26 (10) Physician decision 19 (11) 16 (18) 35 (13) Other 1 (<1) 1 (1) 2 (<1) Median duration of IDELA exposure, mo (range) 12.3 ( ) Median duration of study, mo (range) 13.6 ( ) 5.8 (0-20.0) * Based on investigator choice. Ended study participation prior to PFS event (does not preclude participation in long-term follow-up) Per early amendment, adverse event (AE) was disallowed as valid reason for study discontinuation. Withdrawal from long-term follow-up: n = 9, IDELA + OFA; n = 14, OFA Jones J, et al. J Clin Oncol. 2015;33(suppl): Abstract 7023.

50 Efficacy Summary* IDELA + OFA vs OFA Primary endpoint Secondary endpoints PFS ORR LNR OS HR (95%CI) P value OR (95% CI) P value OR (95%CI) P value HR (95%CI) P value 0.27 (0.19, 0.39) < (7.8, 32.58) < (97.91, ) < (0.44, 1.25).27 Achieved statistical significance per the prespecified sequential testing order PFS in del(17p)/tp5 3 subgroups HR (95%CI) P value 0.32 (0.18, 0.57) <.0001 * All results shown are primary analysis on intention to treat using stratified methods; P<.04 for primary endpoint and P<.03 for secondary endpoints; for PFS and OS, the P values are from stratified log-rank test; for ORR and LNR, P values are from Cochran-Mantel-Haenszel method. CI, confidence interval; OR, odds ratio Jones J, et al. J Clin Oncol. 2015;33(suppl): Abstract 7023.

51 Overall Response Confirmed response* IDELA + OFA, n = 174 OFA, n = 87 Best response, n (%) Complete 1 (<1) 0 Partial 130 (75) 16 (18) Stable disease 31 (18) 51 (59) Progressive disease 1 (<1) 13 (15) Not evaluable 11 (6) 7 (8) Overall response, n (%) 131 (75) 16 (18) Odds ratio (95%CI) 15.9 (7.8, 32.6) P value <.001 * Patients with CR or partial response (PR) who maintained the response for 8 weeks (with 1 interval) were defined to have confirmed response for CR or PR Jones J, et al. J Clin Oncol. 2015;33(suppl): Abstract 7023.

52 Overall Response Rate by Subgroup IDELA + OFA n OFA n Favors IDELA + OFA Overall (7.80, 32.58) Relapsed (4.53, 26.51) Disease Refractory (6.46, 42.65) Mutated (1.84, 20.99) IGHV Unmutated (8.59, 42.50) Del(17p)/TP53 Either (5.07, 44.60) Neither (5.83, 29.12) Del(17p) Yes (2.98, 70.59) No (7.30, 31.36) Sex Male (6.20, 28.67) Female (4.33, 46.46) Age <65 years (5.82, 57.40) >65 years (5.25, 24.90) Race White (6.59, 26.13) Non-white (2.55, ) I ORR odds ratio (95%CI) Favors OFA Jones J, et al. J Clin Oncol. 2015;33(suppl): Abstract 7023.

53 Best Lymph Node Response SPD, sum of products of perpendicular diameters. Red dashed line indicates criterion for lymphadenopathy response (IWCLL) 1 1 Hallek M, et al. Blood. 2008;111(12): Jones J, et al. J Clin Oncol. 2015;33(suppl): Abstract 7023.

54 Progression-Free Survival Jones J, et al. J Clin Oncol. 2015;33(suppl): Abstract 7023.

55 Progression-Free Survival Jones J, et al. J Clin Oncol. 2015;33(suppl): Abstract 7023.

56 Progression-Free Survival by Subgroup IDELA + OFA n OFA n Favors IDELA + OFA Favors OFA Overall (0.19, 0.39) Relapsed (0.26, 0.69) Disease Refractory (0.12, 0.35) Mutated (0.16, 0.87) IGHV Unmutated (0.17, 0.38) Del(17p)/TP53 Either (0.18, 0.57) Neither (0.18, 0.46) Del(17p) Yes (0.09, 0.49) No (0.19, 0.46) Sex Male (0.19, 0.46) Female (0.14, 0.56) Age <65 years (0.16, 0.55) >65 years (0.19, 0.47) Race White (0.21, 0.46) Non-white (0.11, 0.69) I I PFS Hazard Ratio (95%CI) Jones J, et al. J Clin Oncol. 2015;33(suppl): Abstract 7023.

57 Overall Survival Jones J, et al. J Clin Oncol. 2015;33(suppl): Abstract 7023.

58 AE Summary n (%) IDELA + OFA, n=173 OFA, n=86 AE 172 (99) 85 (99) Grade >3 AE 152 (88) 48 (56) AE related to IDELA 155 (90) Grade >3 AE related to IDELA 116 (67) AE related to OFA 136 (79) 67 (78) Grade >3 AE related to OFA 82 (47) 29 (34) SAE 121 (70) 36 (42) SAE related to IDELA 73 (42) SAE related to OFA 39 (23) 17 (20) SAE, serious adverse event Jones J, et al. J Clin Oncol. 2015;33(suppl): Abstract 7023.

59 Common Treatment-Emergent AEs* ( 15% in IDELA + OFA Group) IDELA + OFA, n = 173 OFA, n = 86 n (%) Any Grade Grade >3 Any Grade Grade >3 Any AE 172 (99) 152 (88) 85 (99) 48 (56) Diarrhea 85 (49) 35 (20) 20 (23) 1 (1) Neutropenia 61 (35) 59 (34) 14 (16) 13 (15) Pyrexia 56 (32) 12 (7) 20 (23) 2 (2) Fatigue 55 (32) 6 (3) 24 (28) 4 (5) Cough 52 (30) 1 (<1) 18 (21) 0 Nausea 52 (30) 1 (<1) 23 (27) 1 (1) Rash 49 (28) 7 (4) 9 (11) 2 (2) Constipation 36 (21) 0 13 (15) 1 (1) Anemia 34 (20) 20 (12) 9 (10) 0 Headache 33 (19) 0 9 (10) 0 Upper respiratory tract infection 31 (18) 0 9 (10) 0 Decreased appetite 30 (17) 1 (<1) 7 (8) 1 (1) Pneumonia 30 (17) 22 (13) 11 (13) 7 (8) Dyspnea 29 (17) 7 (4) 10 (12) 1 (1) Infusion-related reaction 29 (17) 4 (2) 23 (27) 1 (1) Edema peripheral 29 (17) 0 9 (10) 0 Insomnia 27 (16) 0 13 (15) 0 Abdominal pain 26 (15) 5 (3) 6 (7) 0 *Using MedDRA Preferred Terms unless otherwise noted. Using Medical Search Term list. Jones J, et al. J Clin Oncol. 2015;33(suppl): Abstract 7023.

60 Treatment-Emergent Laboratory Abnormalities IDELA + OFA, n = 173 OFA, n = 86 n (%) Any Grade Grade >3 Any Grade Grade >3 Anemia 74 (43) 30 (17) 34 (40) 10 (12) Neutropenia 122 (71) 82 (47) 50 (58) 28 (33) Thrombocytopenia 58 (34) 23 (13) 21 (24) 10 (12) ALT/AST elevation 38 (35) 22 (13) 20 (19) 1 (1) *ALT, alanine aminotransferase; AST, aspartate aminotransferase Jones J, et al. J Clin Oncol. 2015;33(suppl): Abstract 7023.

61 n (%) SAEs (>4% in Any Treatment Group)* IDELA + OFA, n = 173 OFA N = 86 Any SAE 121 (70) 36 (42) Preferred Term Febrile neutropenia 20 (12) 3 (3) Pneumonia 20 (12) 9 (10) Pyrexia 19 (11) 1 (1) Diarrhea 17 (10) 0 Neutropenia 13 (8) 2 (2) Sepsis 11 (6) 1 (1) Colitis 9 (5) 0 Anemia 7 (4) 2 (2) Pneumonitis 7 (4) 0 Urinary tract infection 7 (4) 0 TEAEs Leading to IDELA Discontinuation in 2 Patients IDELA + OFA, n (%) n = 173 Discontinued due to AE 53 (31) Preferred Term Diarrhea 11 (6) Pneumonia 5 (3) Alanine aminotransferase increased 4 (2) Pneumonitis 4 (2) Colitis 3 (2) Acute respiratory failure 2 (1) Aspartate aminotransferase increased 2 (1) Bronchopulmonary aspergillosis 2 (1) Febrile neutropenia 2 (1) Lung infection 2 (1) Rash maculopapular 2 (1) *Any grade SAE. Total of 5 patients discontinued for transaminase elevation Jones J, et al. J Clin Oncol. 2015;33(suppl): Abstract 7023.

62 Richter s Transformation and Second Malignancies; Adjusted for Exposure IDELA + OFA, (n = 173) OFA N = 86 Patients with event, n Total exposure time, years Adjusted incidence rate (95% CI) Patients with event, n Total exposure time, years Adjusted incidence rate (95%CI) Richter s transformation ( ) ( ) Second malignancy ( ) ( ) Jones J, et al. J Clin Oncol. 2015;33(suppl): Abstract 7023.

63 Conclusions IDELA + OFA yielded superior PFS, ORR< and LNR, compared with OFA alone in patients of varying fitness levels with previously treated CLL The benefit of combination therapy was shown across all riskrelated stratification groups, including patients with del(17p) CLL The safety profile of IDELA + OFA was manageable, with a resultant similar benefit/risk as seen in previous studies of patients with relapsed CLL Patients in the combination arm exhibited a lower risk of OFA infusion-related reactions Patients in the OFA arm disproportionately discontinued from study prior to disease progression, often to receive alternative therapy; this may have contributed to the similar overall survival in the two treatment groups Jones J, et al. J Clin Oncol. 2015;33(suppl): Abstract 7023.

64 Idelalisib Efficacy and Safety in Follicular Lymphoma Patients From a Phase 2 Study Abstract #8529 Salles G, Schuster SJ, de Vos S, Wagner-Johnston ND, Viardot A, Flowers CR, Will M, Breuleux M, Godfrey WR, Sorensen B, Gopal AK

65 Introduction Approximately 20% of non-hodgkin lymphomas (NHLs) and 60% of indolent NHLs (inhls) are follicular lymphoma (FL), 1,2 considered to be treatable but not curable with current options 3,4 The median age at diagnosis of FL is 65 years 5 The 2008 World Health Organization classification includes grades 1 2, 3a,and 3b 6 Rituximab (R), alone or with chemotherapy, is the recommended first-line therapy for FL 7,8 These regimens are associated with limiting toxicities, 3 and, with time, a substantial proportion of patients develop recurrent or progressive disease (PD) refractory to these treatments 9 Retreatment is usually associated with lower response rates and shorter duration of response vs previous treatment courses 10,11 Patients with FL who relapse within 2 years of treatment (~20%) have reduced overall survival (OS) Glass AG, et al. Cancer. 1997;80(12): Morton LM, et al. Blood. 2006;107(1): Lunning MA and Vose JM. Blood Rev. 2012;26(6): Swenson WT, et al. J Clin Oncol. 2005;23(22): Smith A, et al. Br J Cancer. 2011;105(11): Harris NL, et al. Follicular lymphoma. In: Swerdlow SH, et al, eds. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. Vol 2. 4th ed. Lyon, France: World Health Organization; 2008: Dreyling M, et al. Ann Oncol. 2014;25 Suppl 3:iii National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Non-Hodgkin s Lymphomas (version ) Hainsworth JD, et al. J Clin Oncol. 2005;23(6): Johnson PW, et al. J Clin Oncol. 1995;13(1): Kahl BS, et al. J Clin Oncol. 2014;32(28): Casulo C, et al. Blood. 2013;122(21):510. Salles G, et al. J Clin Oncol. 2015;33(suppl): Abstract 8529.

66 Introduction (cont) There is an unmet need for effective and well-tolerated treatment options in high-risk, relapsed/refractory patients 1,2 Idelalisib, a first-in-class oral selective phosphatidylinositol 3-kinase delta (PI3Kδ) inhibitor, showed antitumor activity and acceptable tolerability as monotherapy in a phase 2 open-label study in inhl refractory to R and an alkylating agent (ClinicalTrials.gov identifier NCT ) 3 1.Johnson PW, et al. J Clin Oncol. 1995;13(1): Kahl BS, et al. J Clin Oncol. 2014;32(28): Gopal AK, et al. N Engl J Med. 2014;370(11): Salles G, et al. J Clin Oncol. 2015;33(suppl): Abstract 8529.

67 Objective This post hoc analysis evaluated the efficacy and safety of idelalisib in highly pretreated patients with relapsed/refractory FL Salles G, et al. J Clin Oncol. 2015;33(suppl): Abstract 8529.

68 Study Design This was a post hoc subgroup analysis of a phase II, multicenter, single-group, open-label study 1 Patients received oral idelalisib 150 mg twice daily (BID) until PD, unacceptable toxicity, or death; dose modification was allowed in patients with adverse events (AEs) 1. Gopal AK, et al. N Engl J Med. 2014;370(11): Salles G, et al. J Clin Oncol. 2015;33(suppl): Abstract 8529.

69 Inclusion Criteria Age 18 years with inhl (FL grade 1, 2, or 3A) treated with 2 prior systemic therapies and refractory to R and an alkylating agent (refractory defined as lack of response to or progression within 6 months of therapy) Eastern Cooperative Oncology Group (ECOG) performance score of 0, 1, or 2 Absolute neutrophil count /L and platelet count /L Exclusion Criteria Histologic transformation, central nervous system lymphoma, hepatic dysfunction, or active systemic infection Salles G, et al. J Clin Oncol. 2015;33(suppl): Abstract 8529.

70 Assessments Tumor assessments were performed at screening; weeks 8, 16, and 24; and every 12 weeks thereafter; response was evaluated by an independent review committee (IRC) The primary outcome was the overall response rate (ORR) Secondary outcomes were lymph node response rate ( 50% decrease in the sum of the products [SPD] of the diameters of index lesions), duration of response (DOR), progression-free survival (PFS), time to response (TTR), OS, health-related quality of life (HRQoL; Functional Assessment of Cancer Therapy: Lymphoma [FACT-Lym]), and safety Salles G, et al. J Clin Oncol. 2015;33(suppl): Abstract 8529.

71 Patient Characteristics and Disposition Patient demographics and baseline disease characteristics were similar to those in the overall study population Of the 72 patients with FL 83.3% had stage III/IV disease 54.2% had a high Follicular Lymphoma International Prognostic Index (FLIPI) risk score 56.9% were ECOG stage 1 or % were refractory to their most recent regimen before the study At the time of data cutoff (June 11, 2014, vs June 25, 2013, for core study publication 1 ), 7 patients (9.7% of 72 FL patients were still on treatment and 65 had discontinued The most frequent reason for discontinuation was PD (progressive disease) (52.8% [n = 38/72]) 1. Gopal AK, et al. N Engl J Med. 2014;370(11): Salles G, et al. J Clin Oncol. 2015;33(suppl): Abstract 8529.

72 Best % Change in SPD Change in Tumor Volume: Best Response Patients with baseline but no follow-up measurement (n = 2) Patients with baseline and follow-up measurement (n = 70) Median (range) treatment duration was 6.5 ( ) months, and median (range) follow-up was 19.4 ( ) months 57% of patients showed a 50% SPD reduction in lymph node size Salles G, et al. J Clin Oncol. 2015;33(suppl): Abstract Patient

73 Best Overall Response in Relapsed/Refractory Patients (n = 72) NE 1% (n = 1) CR 14% (n = 10) PR 42% (n = 30) SD 32% (n = 23) PD 11% (n = 8) ORR was 55.6% (n = 40/72; 95% CI, ; P<.001) overall and 66.7% (n = 8/12; 95% CI, ) in patients with FL grade 3a. At data cutoff, there were 10 (13.9%) complete responses (CRs) overall, including 1 patient with FL grade 3a The disease control rate (CR + partial response [PR] + stable disease [SD]) was 87.5% At the time of first analysis (June 25, 2013), ORR and CR were 54.2% and 8.3%, respectively CR, complete response; NE, not evaluable; PD, progressive disease; PR, partial response; SD, stable disease Salles G, et al. J Clin Oncol. 2015;33(suppl): Abstract 8529.

74 Kaplan-Meier Estimated PFS and OS PFS OS Median (range) PFS for the overall patient population treated with idelalisib was 11.0 (0-30.6) months; 44.7% of patients were progression-free at 1 year Median KM-estimated OS was not reached; median OS was 88.1% at 12 months, 74.2% at 18 months, and 69.8% at 24 months PFS, progression-free survival; OS, overall survival Salles G, et al. J Clin Oncol. 2015;33(suppl): Abstract 8529.

75 Survival Probability Comparison of PFS With Previous Line of Therapy Before Study Inclusion Idelalisib LPT N at Risk (Events) Idelalisib LPT Time, Months 72 (0) 55 (8) 35 (22) 26 (28) 18 (33) 14 (37) 11 (37) 6 (38) 5 (38) 3 (39) 1 (39) 0 (40) 0 (40) 0 (40) 0 (40) 70 (0) 50 (22)28 (43) 17 (54) 9 (62) 7 (64) 6 (65) 4 (67) 4 (67) 2 (69) 2 (69) 2 (69) 1 (70) 1 (70) 0 (71) The median (range) PFS of the most recent regimen before the study was 5.1 ( ) months Salles G, et al. J Clin Oncol. 2015;33(suppl): Abstract 8529.

76 AEs Occurring in 10% of Patients Event, n (%) Any Grade 3 AE 71 (98.6) 47 (65.3) Diarrhea 37 (51.4) 10 (13.9) Cough 23 (31.9) 0 Pyrexia 21 (29.2) 3 (4.2) Fatigue 20 (27.8) 0 Nausea 20 (27.8) 2 (2.8) Dyspnea 14 (19.4) 2 (2.8) Rash 14 (19.4) 2 (2.8) Decreased appetite 13 (18.1) 0 Vomiting 12 (16.7) 2 (2.8) Night sweats 11 (15.3) 0 Upper respiratory tract infection 11 (15.3) 0 Weight decreased 11 (15.3) 0 Abdominal pain 10 (13.9) 2 (2.8) Headache 10 (13.9) 1 (1.4) Back pain 9 (12.5) 1 (1.4) Asthenia 8 (11.1) 0 Constipation 8 (11.1) 0 Pneumonia 8 (11.1) 5 (6.9) AEs resulting in study discontinuation in >1 patient (n=2 each) were diarrea, pneumonitis, and alanine aminotransferase (ALT)/aspartate aminotransferase (AST) elevation (combined elevation). Serious AEs occurred in 35 patients (48.6%); the most common were pyrexia (12.5%), diarrhea (6.9%), pneumonia (5.6%), and colitis (4.2%). Grade 3 diarrhea had a median (range) time to onset of 24.7 ( ) weeks. Salles G, et al. J Clin Oncol. 2015;33(suppl): Abstract 8529.

77 Key Laboratory Findings Event, n (%) Any Grade 3 Neutropenia 37 (51/4) 16 (22.2) Anemia 25 (34.7) 2 (2.8) Thrombocytopenia 17 (23.6) 4 (5.6) Increased ALT/AST 38 (52.8) 10 (13.9) The median (range) time to onset of grade 3 ALT/AST elevations was 6.1 ( ) weeks; all cases resolved after dose interruption Salles G, et al. J Clin Oncol. 2015;33(suppl): Abstract 8529.

78 Health-Related Quality of Life Median best change from baseline in FACT-Lym score showed clinically meaningful improvement (based on minimally important difference thresholds) at least once during follow-up for the emotional well-being, functional well-being, additional concerns, trial outcome index score, and FACT: General total score subscales KM-Estimated Median Time to Improvement and Best Change From Baseline in FACT-Lym Scores Median (Range) FACT-Lym Score Best Change From Baseline* (n=72) Median Time to Improvement, mo (n=72) Minimally Important Difference Physical well-being 1.0 (-12.0 to 11.0) NR (0.0 to 30.6) 2-3 Social/family well-being 1.0 (-4.7 to 11.0) NR (0.0 to 30.6) 2-3 Emotional well-being 3.0 (-9.0 to 12.0) NR (0.0 to 30.6) 2-3 Functional well-being 2.0 (-10.0 to 14.0) NR (0.0 to 30.6) 2-3 Additional concerns 5.0 (-17.0 to 19.0) 4.2 (0.0 to 27.9) 3-5 Trial outcome index score 6.0 (-34.0 to 35.0) 2.8 (0.0 to 30.6) 7-8 FACT-G total score 4.0 (-29.7 to 31.0) 6.9 (0.0 to 30.6) 3-7 FACT-Lym total score 7.5 (-39.0 to 47.0) 1.9 (0.0 to 30.6) FACT-G, Functional Assessment of Cancer Therapy: General; FACT-Lym, Functional Assessment of Cancer Therapy: Lymphoma; KM, Kaplan-Meier; NR, not reached. *Defined as the highest change score postbaseline. Calculated as (date of first symptom improvement date of first dose of idelalisib + 1) Salles G, et al. J Clin Oncol. 2015;33(suppl): Abstract 8529.

79 Conclusions In this post hoc analysis evaluating the efficacy and safety of idelalisib in highly pretreated patients with relapsed/refractory FL, idelalisib monotherapy produced a high rate of OR (55.6% overall and 66.7% in FL grade 3a), including 10 CRs (13.9% of 72 FL patients) Responses were rapid and durable and could improve over time The median PFS (11 months) and median OS (not reached) are impressive in this heavily pre-treated population Compared with the most recent regimen before study entry, the PFS of FL patients who received idelalisib therapy was approximately doubled Idelalisib had a manageable safety profile in this aging and frail patient population with relapsed and refractory disease Patients treated with idelalisib maintained or improved HRQoL outcomes over time and demonstrated a clinically meaningful improvement in quality of life, as assessed by the Additional Concerns (Lym-S) subscale Results from this post hoc analysis of a single-arm trial confirm that the selective PI3Kδ inhibitor idelalisib is beneficial as an oral, chemotherapy-free option for the treatment of heavily pre-treated relapsed/refractory patients with FL Salles G, et al. J Clin Oncol. 2015;33(suppl): Abstract 8529.