LINFOMA DI HODGKIN: RUOLO DEI CHECKPOINT INHIBITORS Armando Santoro - PowerPoint PPT Presentation

LINFOMA DI HODGKIN: RUOLO DEI CHECKPOINT INHIBITORS Armando Santoro

CANCER IMMUNOTHERAPY TODAY TUMORS RESPONSIVE TO ANTI-PD1 OR ANTI-PD-L1 THERAPY � MELANOMA � RCC � NSCLC � UROTHELIAL CANCER � HEAD AND NECK CANCER � MERKEL CELL CARCINOMA � MSI

CHECKMATE-205 : PHASE 2 STUDY WITH NIVOLUMAB IN R/R HL Study Design

CHECKMATE 205 : PHASE II STUDY IN cHL- Cohort B COHORT B NIVO IN ASCT+BV ( 60 PTS) EFFICACY OBJECTIVE RESPONSE: 66.3%, CR 9%, PR 58% MEDIAN DOR: 7.8 MS

CHECKMATE 205 : PHASE II STUDY IN cHL- Cohort B COHORT B NIVO IN ASCT+BV ( 60 PTS)

125 Nivolumab for Relapsed/Refractory Classical Hodgkin Lymphoma After Autologous Transplant: Full Results After Extended Follow-Up of the Phase 2 CheckMate 205 Trial Michelle Fanale, 1 Andreas Engert, 2 Anas Younes, 3 Philippe Armand, 4 Stephen Ansell, 5 Pier Luigi Zinzani, 6 John M Timmerman, 7 Graham P Collins, 8 Radhakrishnan Ramchandren, 9 Jonathon B Cohen, 10 Jan Paul De Boer, 11 John Kuruvilla, 12 Kerry J Savage, 13 Marek Trneny, 14 Scott Rodig, 15 Margaret Shipp, 4 Kazunobu Kato, 16 Anne Sumbul, 16 Benedetto Farsaci, 16 Armando Santoro 17 1 University of Texas MD Anderson Cancer Center, Houston, TX, USA; 2 University Hospital of Cologne, Cologne, Germany; 3 Memorial Sloan Kettering Cancer Center, New York, NY, USA; 4 Dana-Farber Cancer Institute, Boston, MA, USA; 5 Mayo Clinic, Rochester, MN, USA; 6 Institute of Hematology “L. e A. Seràgnoli”, University of Bologna, Bologna, Italy; 7 University of California, Los Angeles, CA, USA; 8 Oxford Cancer and Haematology Centre, Churchill Hospital, Oxford, UK; 9 Barbara Ann Karmanos Cancer Institute, Detroit, MI, USA; 10 Winship Cancer Institute, Emory University, Atlanta, GA, USA; 11 Netherlands Cancer Institute – Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands, on behalf of Lunenburg Lymphoma Phase I/II Consortium (LLPC); 12 University of Toronto and Princess Margaret Cancer Centre, Toronto, ON, Canada; 13 British Columbia Cancer Agency, Vancouver, BC, Canada; 14 Charles University in Prague and General University Hospital in Prague, Prague, Czech Republic; 15 Brigham and Women’s Hospital, Boston, MA, USA; 16 Bristol-Myers Squibb, Princeton, NJ, USA; 17 Humanitas Cancer Center – Humanitas University, Rozzano–Milan, Italy Presented at the 14th International Conference on Malignant Lymphoma (ICML); Lugano, Switzerland; June 14–17, 2017

Change in Target Lesion per IRC >95% of evaluable patients showed a reduction in tumor burden Asterisks (*) denote responders

Best Overall Response After Extended Follow-Up BV naïve BV after auto-HSCT BV before and/or Overall after auto-HSCT (Cohort A) (Cohort B) (Cohort C) N = 243 n = 63 n = 80 n = 100 Objective response per IRC, a % 65 (52, 77) 68 (56, 78) 73 (63, 81) 69 (63, 75) (95% CI) Best overall response per IRC, % Complete remission b 29 13 12 16 Partial remission 37 55 61 53 Stable disease 24 21 15 19 Progressive disease 11 8 10 9 Unable to determine 0 4 2 2 • Per investigator assessment, 33% of patients achieved CR and 39% achieved PR • In post-hoc analyses, responses were similar irrespective of BV treatment sequence a Defined according to 2007 International Working Group criteria. b All CRs were confirmed by FDG-PET scan.

Duration of Response by Best Overall Response 1.0 0.9 Proportion of patients in response CR: 20 (16, NE) months 0.8 0.7 0.6 PR: 13 (9, 17) months 0.5 0.4 0.3 0.2 0.1 0 0 3 6 9 12 15 18 DOR (months) Number of patients at risk 6 36 CR 40 30 25 14 32 99 7 128 57 36 19 PR 76 Cohort A Cohort B Cohort C Overall DOR by cohort n = 63 n = 80 n = 100 N = 243 Median DOR in all responders, months 20 (13, 20) 16 (8, 20) 15 (9, 17) 17 (13, 20) Median DOR in CR patients, months 20 (NE, NE) 20 (4, NE) 15 (8, NE) 20 (16, NE) Median DOR in PR patients, months 17 (9, NE) 11 (7, 18) 13 (9, 17) 13 (9, 17) All values are medians (95% CI); NE = not evaluable

Progression-Free Survival by Best Overall Response 1.0 CR: 22 (19, NE) months 0.9 0.8 0.7 Probability of PFS 0.6 PR: 15 (11, 19) months 0.5 SD: 11 (6, 18) months 0.4 0.3 0.2 0.1 0 0 3 6 9 12 15 18 PFS (months) Number of patients at risk CR 40 40 33 32 27 20 16 PR 128 126 89 71 46 25 21 SD 47 44 25 19 11 8 8 • Median PFS for all 243 patients was 15 (11–19) months All values are medians (95% CI). SD = stable disease

Progression-Free Survival by Cohort 1.0 0.9 0.8 0.7 Probability of PFS 0.6 Cohort A: 18 (11, 22) months 0.5 Cohort B: 15 (11, 20) months 0.4 BV naïve (Cohort A) BV after auto-HSCT (Cohort B) 0.3 Cohort C: 12 (11, 18) months BV before and/or after auto-HSCT (Cohort C) 0.2 0.1 0.0 0 3 6 9 12 15 18 PFS (months) Number of patients at risk Cohort A 63 56 41 36 26 18 14 Cohort B 80 70 50 42 33 27 27 Cohort C 100 85 56 44 25 8 4 All values are medians (95% CI)

KEYNOTE-087 : PHASE 2 STUDY WITH PEMBROLIZUMAB IN R/R HL Cohort 2 Cohort 1 Cohort 3 Salvage chemotherapy ASCT and ASCT but not BV and BV subsequent BV (ineligible for ASCT) Chen et al., Journal of Clinical Oncology 25 April 2017

KEYNOTE-087 : PHASE 2 STUDY WITH PEMBROLIZUMAB IN R/R HL Decrease from baseline in tumor burden (le@) and Kaplan-Meier esDmates of objecDve response duraDon (right) on the basis of central review in paDents with response. All cohorts Tumor burden ObjecDve response duraDon Chen et al., Journal of Clinical Oncology 25 April 2017

RUOLO DEL TRAPIANTO CONSOLIDARE LA RISPOSTA CON IL TRAPIANTO ? AUTOLOGO? ALLOGENICO?

CHECKMATE-205 : PHASE 2 STUDY WITH NIVOLUMAB IN R/R HL Study Design

NIVOLUMAB IN HODGKIN’S LYMPHOMA

KEYNOTE-087 : PHASE 2 STUDY WITH PEMBROLIZUMAB IN R/R HL Cohort 2 Cohort 1 Cohort 3 Salvage chemotherapy ASCT and ASCT but not BV and BV subsequent BV (ineligible for ASCT) Chen et al., Journal of Clinical Oncology 25 April 2017

KEYNOTE-087 : PHASE 2 STUDY WITH PEMBROLIZUMAB IN R/R HL COHORT B INELIGIBLE TO ASCT → → → → → → → → → → → → → 100 → → → → → 90 → → → → Cumulative Event Rate, % → 80 → → → → → 70 → → → → → 60 → → → → → 50 → → → → → → 40 → → → Treatment Ongoing → → 30 → Complete Response → → 20 → → Partial Response → Progressive Disease → 10 + + Last Dose → → Death 0 → → → 0 3 6 9 12 15 → → → Months → → n at risk → → Months → 52 31 9 0 0 0 • Median (range) time to response • Median number of treatment cycles • 2.8 (2.2-5.6) months • 12 (range 1, 21) • Response duration ≥ 6 months: 70%

Clinical Evaluation of PD-1 Blockade Relapsed/Refractory cHL

RUOLO DEL TRAPIANTO: PD-1 In POST-ALLO ALLOGENICO PD-1 In

IPILIMUMAB AFTER ALLOTRANSPLANT IN HL Davids MS et al, NEJM 2016

September 18 th , 2017 Charles Herbaux et al. This study retrospecDvely assessed the efficacy and toxicity of nivolumab (PD-1 pathway blocking monoclonal anDbody) as a single agent in 20 HL paDents relapsing a@er allo-HCT Key Points: • PD-1 blockade with nivolumab provides durable disease control a@er allo-HCT • PD-1 blockade with nivolumab a@er allo-HCT is associated with 30% acute GVHD

Bradley M. Haverkos et al. PD-1 blockade for relapsed lymphoma post–allogeneic hematopoie^c cell transplant: high response rate but frequent GVHD Key Points • Checkpoint blockade via anD–PD-1 mAbs was associated with a high overall response rate in relapsed HL allo-HCT paDents. • Checkpoint blockade via anD–PD-1 mAbs a@er allo- HCT can be complicated by rapid onset of severe and treatment- refractory GVHD.

RUOLO DEL TRAPIANTO: ALLO POST-PD1 IN ALLOGENICO?

CHECKMATE-205 : PHASE 2 STUDY WITH NIVOLUMAB IN R/R HL COHORT B NIVO IN ASCT+BV ( 60 PTS)

Progression-Free Survival by Cohort 1.0 0.9 0.8 0.7 Probability of PFS 0.6 Cohort A: 18 (11, 22) months 0.5 Cohort B: 15 (11, 20) months 0.4 BV naïve (Cohort A) BV after auto-HSCT (Cohort B) 0.3 Cohort C: 12 (11, 18) months BV before and/or after auto-HSCT (Cohort C) 0.2 0.1 0.0 0 3 6 9 12 15 18 PFS (months) Number of patients at risk Cohort A 63 56 41 36 26 18 14 Cohort B 80 70 50 42 33 27 27 Cohort C 100 85 56 44 25 8 4 M. Fanale et al ICML 2017 All values are medians (95% CI)

KEYNOTE-087 : PHASE 2 STUDY WITH PEMBROLIZUMAB IN R/R HL Decrease from baseline in tumor burden (le@) and Kaplan-Meier esDmates of objecDve response duraDon (right) on the basis of central review in paDents with response. All cohorts Tumor burden ObjecDve response duraDon Chen et al., Journal of Clinical Oncology 25 April 2017

ASH 2016