Kidney Cancer Session

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1 New Frontiers in Urologic Oncology September 12 th, 2015 Kidney Cancer Session Moderator: Philippe E. Spiess, M.D. Invited Faculty Members: Wade J. Sexton, MD Jeremiah J. Morrissey, PhD

2 Agenda for Session 1:00-1:20 Emerging Systemic Therapies in Metastatic Kidney Cancer: Immune Checkpoint Regulators? Philippe Spiess, M.D. (Moffitt Cancer Center) 1:20-1:40 Implications of the Human Genome Atlas in the Management of Kidney Cancer? Wade J. Sexton, M.D. (Moffitt Cancer Center) 1:40-2:00 Novel Urinary Markers in the Diagnosis and Management of Kidney Cancer Jeremiah J. Morrissey, PhD (Washington University in St Louis) 2:00-2:45 Case Discussion with Panel

3 New Frontiers in Urologic Oncology September 12 th, 2015 Emerging Systemic Therapies in Metastatic Kidney Cancer: Immune Checkpoint Regulators Philippe E. Spiess, MD, FACS Associate Member Department of GU Oncology Moffitt Cancer Center NCCN Bladder and Penile Cancer, Vice-Chair

4 Checkpoint Charlie- Dividing East and West Germany

5 Why are PD-1/PD-L1 drugs so exciting? Postow MA et al. JCO, 2015

6 PD-L1 Inhibitors- multiple targets Chen DS, et al. Clin Cancer Res, 18:6580, 2012

7 PD-1 and PD-L1 Ab in development Postow MA et al. JCO, 2015

8 Gauging Treatment Response with these agents is different Postow MA et al. JCO, 2015

9 Preliminary data on PD-L1 inhibitors Study by Choueiri et al evaluating whether PDL-1 expression could predict response to TKI therapy (using data obtained from the COMPARZ trial of sunitinib/pazopanib) Tissue from 453 mrcc Pts were available, 64% of Pts were were negative for PDL-1 expression Patients with high PDL-1 expression (using IHC staining and H-scoring) were associated with worse OS (median of 15.1 vs 35.6 months in sunitinib arms and 15.3 vs 27.8 months in pazopanib arms, P= 0.03) PFS rates were similar based on PDL-1 expression patterns Choueiri TK et al. Clin Cancer Res 21:1071, 2014

10 Preliminary data on PD-L1 inhibitors Choueiri TK et al. Clin Cancer Res 21:1071, 2014

11 Preliminary data on PD-L1 inhibitors Recent phase II trial published by Motzer et al evaluating the role of nivolumab (PD-1 inhibitor) in mrcc Pts with clear cell components treated previously with VEGF inhibitor Patients were blinded and treated in a 1:1:1 ratio of incremental increases in nivolumab dosing (0.3, 2, 10 mg/kg iv 1x/q3 weeks) Primary objective was assessing dose response using PFS with secondary endpoints of OS, ORR, and safety 168 Pts were treated with median PFS in sequential arms being 2.7, 4.0, and 4.2 months, respectively (P=0.9) Median OS was 18.2, 25.5, and 24.7 months, respectively Only 19 Pts (11%) experienced grade 3-4 adverse events Motzer RJ et al. JCO 33:1430, 2014

12 Preliminary data on PD-L1 inhibitors Motzer RJ et al. JCO 33:1430, 2014

13 Preliminary data on PD-L1 inhibitors Motzer RJ et al. JCO 33:1430, 2014

14 Preliminary data on PD-L1 inhibitors Motzer RJ et al. JCO 33:1430, 2014

15 Exciting Phase II data Phase II prospective study conducted by McDermott et al. of 34 mrcc patients previously treated from who received nivolumab (1 or 10 mg/kg) as outpatients (q 2 weeks for up to 96 weeks) Patients were observed for survival and duration of treatment response after discontinuing treatment 10 Pts (29%) achieved an objective response, with median duration of response 12.9 months 9 Pts (27%) exhibited a stable response lasting > 24 weeks 3 of 5 Pts who stopped treatment while exhibiting a response, remained responders > 45 weeks McDermott DF et al. JCO, 2015

16 Exciting Phase II data Median overall response in all Pts (71% of which had received 2 to 5 prior systemic agents) was 22.4 months Reported 1, 2, and 3 yr OS rates were 71%, 48%, and 44%, respectively Grade 3 to 4 treatment related AE occurred in 18%, all of which were reversible McDermott DF et al. JCO, 2015

17 Exciting Phase II data McDermott DF et al. JCO, 2015

18 Exciting Phase II data McDermott DF et al. JCO, 2015

19 Exciting Phase II data McDermott DF et al. JCO, 2015

20 Recent Phase II study McDermott DF et al. JCO, 2015

21 Impressive response to PD-L1 62 year old with prior sorafenib treatment, and prior IFN/IL2 now 7 years out from original cytoreductive nephrectomy 6/2012 before start 8/2012 loss of enhancement Courtesy of Dr Mayer Fishman- personal communication

22 Impressive response to PD-L1 #3 regression #4 durability Courtesy of Dr Mayer Fishman- personal communication

23 Conclusions Checkpoint inhibitors offer great promise as novel agents that can impact the natural history of mrcc These agents have excellent biological activity for other epithelial neoplasms and the preliminary data in mrcc is promising Toxicity profile of these agents is quite favorable making them appealing Based on their unique mechanistic properties, they can be combined with other systemic agents (e.g. TKI, mtor inhibitors) potentially resulting in synergistic and meaningful treatment responses (prolonged CR or PR)

24 References 1. Postow MA, Callahan MK, Wolchok JD. Immune checkpoint blockade in cancer therapy. Journal of Clinical Oncology, 33:17, Motzer RJ, Rini BI, McDermott DF, et al. Nivolumab for metastatic renal carcinoma: Results of a randomized Phase II trial. Journal of Clinical Oncology, 33:13, McDermott DF, Drake CG, Sznol M, et al. Survival, durable response, and long-term safety in patients with previously treated advanced renal carcinoma receiving nivolumab. Journal of Clinical Oncology. 33:18: Choueiri TK, Figueroa DJ, Fay AP, et al. Correlation of PD-L1 tumor expression and treatment outcomes in patients with renal cell carcinoma receiving sunitinib or pazopanib: Results from COMPARZ, a randomized controlled trial. Clinical Cancer Research, 21: , 2014.

25 TAMPA BAY LIGHTNING 2015 EASTERN CONFERENCE FINAL CHAMPIONS