A CME-certified Oncology Exchange Program

Transcription

1 A CME-certified Oncology Exchange Program Jointly provided by Potomac Center for Medical Education and Rockpointe Supported by an educational grant from Seattle Genetics, Inc.

2 Re-treatment with BV Bartlett et al., J of Hematolgoy Oncology 2014

3 Pet-adapted Sequential Salvage Therapy With BV Followed By Augmented ICE For Patients With Relapsed And Refractory HL A Non-Randomized, Open-label, Single-centre, Phase 2 Study Moskowitz A et al., 2015, The Lancet Oncology, 16(3),

4 Pet-adapted Sequential Salvage Therapy With BV Followed By Augmented ICE For Patients With Relapsed And Refractory HL A Non-Randomized, Open-label, Single-centre, Phase 2 Study Tumour reduction after BV. Data shows PET status according to the Deauville scores of 1 5. Overall Survival (A), Event-free Survival (B), And Event-free Survival For Patients Who Received Transplantation, According To Their PET Status And Treatment Group (C) Moskowitz A et al., 2015, The Lancet Oncology, 16(3),

5 Overall Survival (A), Event-free Survival (B), And EFS For Patients Who Received Transplantation, According To Their PET Status And Treatment Group (C) Moskowitz A et al., 2015, The Lancet Oncology, 16(3),

6 Summary 76 % PET-negative (CR) achieved with PET adapted sequential therapy with BV and augmented ICE 27% patients avoided ICE salvage therapy HDT/ASCT outcomes were identical for patients who achieved PET-negative status after one or two sequential salvage regimens. The findings from this trial imply the goal of salvage therapy should be attainment of PET-negative status before HDT/ASCT for patients with relapsed or refractory Hodgkin's lymphoma. Moskowitz A et al., 2015, The Lancet Oncology, 16(3),

7 BV as Consolidation post-asct In Patients With HL At Risk Of Relapse Or Progression (AETHERA) A Randomized, Double-blind, Placebo-controlled, Phase 3 Trial *Two patients allocated to the placebo group received a dose of brentuximab vedotin. Moskowitz C, et al. The Lancet, 2015.

8 PFS and OS Independent Review Investigator Assessment Interim Analysis of Overall Survival Moskowitz C, et al. The Lancet, 2015.

9 Subgroup Analysis of PFS by Independent Review Moskowitz C, et al. The Lancet, 2015.

10 Immunomodulation in HL: A novel approach PD-1 Pathway and immune surveillance PD-1 is expressed on the surface of activated T cells 1 Its ligands, PD-L1 and PD-L2, are overexpressed in certain tumor cells 1 Binding of PD-1 to its ligands inhibits T-cell activation, allowing tumors to evade the immune response 2 Pardoll et al Nat Rev Cancer. 2012; 2. Keir et al. Annu Rev Immunol. 2008

11 PD-L1 Almost Universally Expressed on RS Cells Through 9p24.1 Amplification or EBV > 80% expression in HL Green, et al. Blood 2010, Green, et al. CCR 2012.

12 PD-1/PD-L1 Inhibitors in Development For Lymphoma PD-1 inhibitors Nivolumab Fully human IgG4 anti-pd-1 antibody Pembrolizumab Humanized IgG4 anti-pd-1 antibody FDA approved for advanced or unresectable melanoma (September 2014) Pidilizumab Humanized anti-pd-1 IgG1 antibody Evaluated as maintenance following ASCT in high risk relapsed/refractory DLBCL (Armand, et al. JCO 2013) PD-L1 inhibitors MED14736 (MedImmune) MPDL3280A (Genentech/Roche)

13 Comparison of Agents Nivolumab (n=23) Abstract 289 Pembrolizumab (n=31) Abstract 290 Dose 1mg/kg 3mg/kg 10 mg/kg IV q 2 wk Week 1,4 and then q 2 % Prior ASCT % Prior Brentuximab % Grade 3 Toxicity Lymphopenia, elevated lipase, colitis, pneumonitis Hypoxia, pneumonitis, joint swelling, axillary pain Grade 4 Toxicity 0 0 PD-L1 expression in samples tested 100% 100%

14 ASH 2014: Anti PD-1 Antibody Relapsed/Refractory HL, Brentuximab Failures Nivolumab: BMS Pembrolizumab:MK-3475 ORR 87%, CR 17% 6 m PFS 86%, med DOR NR Armand et al abstract 289 ORR 66% CR 21% med DOR NR ( d) Moskowitz et al abstract 290

15 Anti-PD-1 Take Home Points Significant activity seen with anti-pd-1 therapy in Hodgkin lymphoma Nivolumab: 87% ORR, 17% CR, 13% SD Pembrolizumab: 66% OR, 21% CR, 45% SD Both drugs with acceptable toxicity profile Breakthrough designation granted for nivolumab in HL International phase II study of nivolumab in HL is ongoing