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1 post Chicago 2016: Thoraxonkologie Helge Bischoff Thoraxonkologie, Thoraxklinik Universität Heidelberg

2 Post Chicago 2016: Thoraxonkologie Immuntherapie SCLC Mesotheliom Nachsorge

3 Pembro/ Carbo/Taxol Pembro/ Carbo/Taxol/ Bev Pembro/ Carbo/Pem

4 CheckMate 032: Nivolumab Alone or in Combination With Ipilimumab for the Treatment of Recurrent Small Cell Lung Cancer Scott J. Antonia, 1 José A. López-Martin, 2 Johanna Bendell, 3 Patrick A. Ott, 4 Matthew Taylor, 5 Joseph Paul Eder, 6 Dirk Jäger, 7 Margaret K. Callahan, 8 Dung T. Le, 9 Filippo de Braud, 10 Michael A. Morse, 11 Paolo A. Ascierto, 12 Leora Horn, 13 Asim Amin, 14 Rathi N. Pillai, 15 Jeffry Evans, 16 Chris Harbison, 17 Chen-Sheng Lin, 17 Marina Tschaika, 17 Emiliano Calvo 18 1 H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA; 2 Hospital Universitario 12 de Octubre, Madrid, Spain; 3 Sarah Cannon Research Institute/Tennessee Oncology, PLLC, Nashville, TN, USA; 4 Dana-Farber Cancer Institute, Boston, MA, USA; 5 Oregon Health & Science University, Portland, OR, USA; 6 Yale Comprehensive Cancer Center, New Haven, CT, USA; 7 Nationales Centrum für Tumorerkrankungen (NCT), University Medical Center, Heidelberg, Germany; 8 Memorial Sloan Kettering Cancer Center, New York, NY, USA; 9 The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD, USA; 10 Fondazione IRCCS Instituto Nazionale dei Tumori Milano, Milan, Italy; 11 Duke University Medical Center, Durham, NC, USA; 12 Istituto Nazionale Tumori Fondazione Pascale, Naples, Italy; 13 Vanderbilt-Ingram Cancer Center, Nashville, TN, USA; 14 Levine Cancer Institute, Carolinas Medical Center, Charlotte, NC, USA; 15 Winship Cancer Institute of Emory University, Atlanta, GA, USA; 16 University of Glasgow, Glasgow, UK; 17 Bristol-Myers Squibb, Princeton, NJ, USA; 18 START Madrid, Centro Integral Oncológico Clara Campal, Madrid, Spain

5 Nivolumab +/- Ipilimumab in Recurrent SCLC: CheckMate 032 Study Design SCLC (N = 216) with progressive disease after 1 prior line of therapy, including a first-line platinum-based regimen (unselected by PD-L1 expression) Nivolumab 1 mg/kg + Nivolumab 3 mg/kg IV Q2W Ipilimumab 3 mg/kg IV Q3W (n = 98) for 4 cycles (n = 61) Nivolumab 3 mg/kg + Ipilimumab 1 mg/kg IV Q3W for 4 cycles (n = 54) Nivolumab 3 mg/kg IV Q2W 5

6 Nivolumab +/- Ipilimumab in Recurrent SCLC: Treatment- Related AEs in 10% of Patients Nivolumab-3 (n = 98) Nivolumab-1 + Ipilimumab-3 (n = 61) Nivolumab-3 + Ipilimumab-1 (n = 54) Any grade, % Grade 3 4, % Any grade, % Grade 3 4, % Any grade, % Grade 3 4, % Total treatment-related AEs Fatigue Pruritus Diarrhea Nausea Decreased appetite Hypothyroidism Hyperthyroidism Rash Rash, maculopapular Lipase increased Treatment-related AEs leading to discontinuations Two treatment-related deaths occurred in the nivolumab-1 + ipilimumab-3 arm: one due to myasthenia gravis and one due to worsening of renal failure. One treatment-related death due to pneumonitis occurred in the nivolumab-3 + ipilimumab-1 arm Treatment-related limbic encephalitis was reported in 2 (1%) patients; 1 case resolved, and outcome for 1 case was not reported Treatment-related pneumonitis occurred in 8 (4%) patients; 6 cases resolved, outcome for 1 case is unknown, and 1 case was fatal 6

7 Nivolumab +/- Ipilimumab in Recurrent SCLC: Summary of Response Objective response rate, % (n/n) Overall Platinum-sensitive a Platinum-resistant a Best overall response, % Complete response Partial response Stable disease Progressive disease Unable to determine Not evaluable (no tumor assessment follow-up) Nivolumab-3 (n = 98) 10 (10/98) 11 (6/55) 10 (3/30) Nivolumab-1 + Ipilimumab-3 (n = 61) 23 (14/61) 28 (7/25) 17 (4/23) Nivolumab-3 + Ipilimumab-1 (n = 54) 19 (10/54) 19 (4/21) 10 (2/21) a Platinum sensitivity was unknown for 29 patients as follows: nivo-3, n = 10; nivo-1/ipi-3, n = 11; nivo-3/ipi-1, n = 8. 3 pts in the nivo-3 arm, 2 pts in the nivo-1/ipi-3 arm, and 4 pts in the nivo-3/ipi-1 arm did not receive first-line platinum therapy and did not meet eligibility criteria, although they were treated and included in the analysis

8 Response in a Patient Treated With Nivolumab-1 + Ipilimumab-3 Before treatment After treatment 8

9 Nivolumab +/- Ipilimumab in Recurrent SCLC: Kinetics of Response Nivolumab-3 Nivolumab-1 + Ipilimumab-3 Nivolumab-3 + Ipilimumab-1 Percentage Change From Baseline (%) Time (Weeks) Time (Weeks) Time (Weeks) Confirmed PR or CR First occurrence of new lesion Patients off treatment % change truncated to 100% 9

10 Nivolumab +/- Ipilimumab in Recurrent SCLC: Tumor Response by PD-L1 Expression Nivolumab-3 Nivolumab-1 + Ipilimumab-3 Nivolumab-3 + Ipilimumab Best change from baseline in target lesion volume (%) Patients Patients Patients <1% PD-L1 1% PD-L1 PD-L1 not evaluable/missing Confirmed responders % change truncated to 100% 69% were evaluable for PD-L1 expression at baseline; 16% had 1% tumor PD-L1 expression Responses were seen regardless of PD-L1 expression 1 0

11 Nivolumab +/- Ipilimumab in Recurrent SCLC: Overall Survival Nivolumab-3 Events/ Number at risk 60/98 mos, months year OS rate, % 33 Median a follow-up, mo Nivolumab-1/ipilimumab-3 Nivolumab-3/ipilimumab-1 36/61 35/ OS (%) Time (Months) a Defined as time from first dose to date of DBL; follow-up was shorter for patients who died prior to DBL 1 1

12 Nivolumab +/- Ipilimumab in Recurrent SCLC: Conclusions Nivolumab or Nivolumab plus Ipilimumab Safety profiles similar to that seen in other diseases Higher rates of AEs occurred with combination therapy 7% 11% of patients in the combination cohorts discontinued due to toxicity Treatment-related limbic encephalitis occurred in 2 patients and resolved in 1 patient Three treatment-related deaths (myasthenia gravis, worsening of renal failure, and pneumonitis) Immune-related AEs were managed using established safety guidelines Durable objective responses in patients with relapsed SCLC Tumor responses occurred regardless of platinum sensitivity or tumor PD-L1 expression Survival results were encouraging Nivolumab 1 mg/kg plus ipilimumab 3 mg/kg Q3W is the regimen selected for phase 3 study FAZIT SCLC: nach 30 Jahren ACO / Carbo Eto: neue Hoffnung

13 Tremelimumab as 2nd- or 3rd-line treatment of unresectable malignant mesothelioma: Results from the global, double-blind, placebo-controlled DETERMINE study Presented By Hedy Kindler at 2016 ASCO Annual Meeting

14 Tremelimumab in Mesothelioma Presented By Hedy Kindler at 2016 ASCO Annual Meeting

15 DETERMINE Study Design Global, Randomized, Double-Blind, Placebo-Controlled, Phase 2b Trial Presented By Hedy Kindler at 2016 ASCO Annual Meeting

16 Investigator-assessed PFS (ITT Population) Presented By Hedy Kindler at 2016 ASCO Annual Meeting

17 Antitumor Activity (ITT Population) Presented By Hedy Kindler at 2016 ASCO Annual Meeting

18 Most Frequent Grade 3 AEs Presented By Hedy Kindler at 2016 ASCO Annual Meeting

19 DETERMINE: Conclusions (1) Presented By Hedy Kindler at 2016 ASCO Annual Meeting

Avelumab (MSB0010718C; anti-pd-l1) in patients with advanced unresectable mesothelioma from the JAVELIN Solid Tumor

20 Avelumab (MSB C; anti-pd-l1) in patients with advanced unresectable mesothelioma from the JAVELIN Solid Tumor phase 1b trial: safety, clinical activity, and PD-L1 expression Presented By Raffit Hassan at 2016 ASCO Annual Meeting

21 JAVELIN Solid Tumor: an international, phase 1, multicohort dose-escalation and dose-expansion trial Presented By Raffit Hassan at 2016 ASCO Annual Meeting

22 Patients and treatment Presented By Raffit Hassan at 2016 ASCO Annual Meeting

23 Potential immune-mediated TRAEs Presented By Raffit Hassan at 2016 ASCO Annual Meeting

24 Clinical activity of avelumab Presented By Raffit Hassan at 2016 ASCO Annual Meeting

25 Percent change in target lesions from baseline Presented By Raffit Hassan at 2016 ASCO Annual Meeting

26 Conclusions Fazit Meso: Positive Daten zu Checkpoint Inhibitoren für Pembrolizumab, Avelumab, Nivolumab (IMIG 2016) Immuntherapie als 4th Line Option nach Kostenanfrage Presented By Raffit Hassan at 2016 ASCO Annual Meeting

27 Improved Overall Survival in Lung Cancer Patients using a Webapplication-mediated Follow-up compared to Standard Modalities: Results of a Phase III Randomized Trial Presented By Fabrice Denis at 2016 ASCO Annual Meeting

28 Follow-up and Patient-reported Outcome Presented By Fabrice Denis at 2016 ASCO Annual Meeting

29 Web-mediated follow-up Presented By Fabrice Denis at 2016 ASCO Annual Meeting

30 Phase 3 multi-centric randomized study Presented By Fabrice Denis at 2016 ASCO Annual Meeting

31 CONSORT Diagram Presented By Fabrice Denis at 2016 ASCO Annual Meeting

32 Results: Alert / Relapse description Presented By Fabrice Denis at 2016 ASCO Annual Meeting

33 Overall Survival Improvement Presented By Fabrice Denis at 2016 ASCO Annual Meeting

34 Performance status at relapse Presented By Fabrice Denis at 2016 ASCO Annual Meeting

35 Relapse rates: 51% (control arm) vs 49% (Web-app arm), p=ns No differences in progression-free survival Presented By Fabrice Denis at 2016 ASCO Annual Meeting

36 Compliance - Management Presented By Fabrice Denis at 2016 ASCO Annual Meeting

37 Conclusion Fazit: Zielgerichtete Therapie zielgerichtete Nachsorge Nachsorge 2.0? Presented By Fabrice Denis at 2016 ASCO Annual Meeting

38 Post Chicago 2016: Thoraxonkologie: FAZIT SCLC Mesotheliom Nachsorge Viele interessante Aspekte Keine practice changing Daten

Efficacy and safety of nivolumab plus ipilimumab in previously treated metastatic urothelial carcinoma

Efficacy and safety of nivolumab plus ipilimumab in previously treated metastatic urothelial carcinoma First results from the phase I/II CheckMate 032 study Padmanee Sharma, 1 Margaret K. Callahan, 2 Emiliano