Slide 1: Final Results from a Phase 2 Study of Pracinostat with Azacitidine in Elderly AML
G Garcia-Manero1, E Atallah2, B Medeiros3, M Arellano4, SK Khaled5, M Patnaik MD6, O Odenike7, SH Sayar8, MK Tummala9, P Patel10, L Maness-Harris11, R Stuart12, E Traer13, K Karamlou14 and A Yacoub15 1 University of Texas MD Anderson Cancer Center, Houston, TX; 2Medical College of Wisconsin, Milwauk
Slide 2: Aza + Pracinostat in AML: Introduction
Aza + Pracinostat in AML: Introduction Elderly AML patients, deemed unsuitable for intensive therapy, have limited treatment options Pracinostat is a potent hydroxamic acid based oral HDAC inhibitor selective for class I, II and IV isoforms The combination of azacitidine and pracinostat synergistic
Slide 3: Aza + Pracinostat in AML: Study Design
Elderly (Age ≥ 65 years) Patients with Newly Diagnosed AML Aza + Pracinostat in AML: Study Design Pracinostat + Azacitidine 50 patients enrolled at 15 sites in the U.S. Last patient in on November 24, 2014 Primary endpoint: CR + CRi + MLFS* Secondary endpoints: ORR, CCyR, duration of response, EFS,
Slide 4: Eligibility Criteria
Key Inclusion Age ≥65 years Newly diagnosed de novo, secondary, or treatment-related AML Intermediate or unfavorable-risk cytogenetics (SWOG classification: Slovak et al, 2000) ≥ 20% bone marrow blasts Adequate renal, cardiac and liver function QTcF <450 ms for males or <470 ms for females Key Exclu
Slide 5: Treatment Regimen
Aza + Pracinostat in AML: Treatment Regimen Azacitidine 7 days (days 1-7) 75 mg/m2 IV/sq 28-day cycle Pracinostat 60 mg orally 3 days a week for 21 days on 28 day cycle Dose Modifications: Reductions Azacitidine for myelosuppresion Pracinostat: non-Heme toxicity Delays (between or within cycles) ≥Gr
Slide 6: Patient Characteristics
Pracinostat + Azacitidine n=50 % Age, Years Median 76 Min-max 67-84 ≥75 50 Male gender 58 AML classification (by WHO) Not otherwise specified 44 With myelodysplasia-related changes 40 With therapy-related myeloid neoplasms 10 With recurrent genetic abnormalities* 6 Prior MDS Yes 24 Secondary 10 No 6
Slide 7: Patient Characteristics
Pracinostat + Azacitidine (n=50) % BM blasts Median 40 Min-max 20 – 89 ECOG PS 0 - 1 84 2 16 Cytogenetic risk group Intermediate 54 Intermediate, cytogenetically normal 42 Poor* 42 *The poor risk category for MEI-004 was defined using Southwest Oncology Group (SWOG) and Medical Research Council Cyto
Slide 8: Patient Characteristics
Pracinostat + Azacitidine (n=50) WBC (x 109/L) Median 2.6 Min-max 0.8 – 29.6 Hemoglobin (g/dL) Median 9.2 Min-max 6.5 – 14.9 Platelets (x 109/L) Median 47 Min-max 11-643 Peripheral Blasts (x 109/L) Median 0.2 Min-max 0 – 8.5 Serum Creatinine (mg/dL) Median 0.6 Min-max 0.2 – 1.5 Total Bilirubin (mg/d
Slide 9: Aza+Pracinostat in AML: Patient Disposition
n=50 (%) Number of Patients Alive Number of Patients Active Median Observation Time: 14.3 months 28 (56) 11 (22) Number of Patients Discontinued Reasons for discontinuation: Progressive Disease Adverse Event Other* 39 (50) 15 (30) 11 (22) 13 (26) Aza+Pracinostat in AML: Patient Disposition 50 patien
Slide 10: TEAEs in ≥25% of Patients (all causality)
Aza+ Pracinostat in AML: TEAE’s in ≥25% of Patients (all causality) All Grades (%), n=50 Grades 3-4 (%), n=50 Hematologic Febrile Neutropenia 24 (48.0) 20 (40.0) Thrombocytopenia 22 (44.0) 22 (44.0) Anemia 18 (36.0) 15 (30.0) Neutropenia 17 (34.0) 17 (34.0) Non-Hematologic Nausea 38 (76.0) 3 (6.0) C
Slide 11: Treatment Emergent Adverse Events Leading to Drug Discontinuation
Treatment Emergent Adverse Events Leading to Drug Discontinuation (n=11) AE Term Grade Discontinuation (Cycle/Day) Outcome Intermittent Fatigue 1 4/28 Resolved Acute Kidney Injury 1 3/7 Not Resolved Peripheral Motor Neuropathy 3 3/15 Resolved Intermittent Fatigue 3 4/28 Not Resolved Parainfluenza 3
Slide 12: Response
Aza + Pracinostat in AML: Response Response Assessment Cytogenetic Risk* All n=50(%) Intermediate n=27(%) High n=21(%) CR/CRi/MLFS (Primary endpoint) 28 (56) 17 (81) 11 (52) CR 21 (42) 15 (56) 6 (29) CRi 2 (4) 0 (0) 2 (10) MLFS 5 (10) 2 (7) 3 (14) *2 not evaluable for cytogenetic risk assessment CR,
Slide 13: Overall Survival
Aza + Pracinostat in AML: Overall Survival
Slide 14: Aza+ Pracinostat in AML OS by Cytogenetic Risk
Aza+ Pracinostat in AML OS by Cytogenetic Risk
Slide 15: Association of Survival with CR
Aza + Pracinostat in AML: Association of Survival with CR
Slide 16: MEI-004 vs. AZA-001: Baseline Characteristics
MEI-004 AZA-0011 Pracinostat + Azacitidine (n=50) Azacitidine (n=241) Age, Years Median 76 75 Min-max 67-84 64-91 ≥75 50 57 Male gender 58 57.7 AML classification (by WHO) Not otherwise specified 44 63.5 With myelodysplasia-related changes 40 31. With therapy-related myeloid neoplasms 10 3.3 With re
Slide 17: MEI-004 vs. AZA-001: Baseline Characteristics
MEI-004 AZA-0011 Pracinostat + Azacitidine (n=50) Azacitidine (n=241) BM blasts Median 40 70 Min-max 20 – 89 2 - 100 ECOG PS 0 - 1 84 77.2 2 16 22.8 Cytogenetic risk group Intermediate 54 64.3 Intermediate, cytogenetically normal 42 46.9 Poor 42 35.3 1Dombret et al. Blood. 2015 Jul 16;126(3):291-9 M
Slide 18: MEI-004 vs. International Phase III Study of Azacitidine (AZA-001)
AZA-001 MEI-004 Conventional Care Regimens Azacitidine Pracinostat + Azacitidine High-Risk Population1 n=85 n=85 n=21 1-year survival estimate 14 30.9 57 Median overall survival 3.2 months 6.4 months 13.3 months Overall Population2 n=247 n=241 n=50 CR rate 21.9 19.5 42 60-day mortality rate 18.2 16.
Slide 19: Aza+ Pracinostat in AML: Conclusions
Aza+ Pracinostat in AML: Conclusions Combination of Aza+ Pracinostat is safe in elderly AML High response rate compared to single agent Azacitidine Potential for prolongation of survival Apparent correlation of CR and survival in this low intensity therapy Future plans: Additional analysis genomic a
Slide 20: Acknowledgements
Acknowledgements This work was supported by MEI Pharma, Inc.