1) A phase 3 trial compared nivolumab to everolimus in advanced renal cell carcinoma patients who had received 1-2 prior anti-angiogenic therapies. Nivolumab demonstrated significantly longer overall survival compared to everolimus, with median overall survival of 25 months versus 19.6 months. 2) Nivolumab had a higher objective response rate compared to everolimus (25% vs 5%) and longer median duration of response. 3) The overall survival benefit of nivolumab was consistent across patient subgroups and was independent of PD-L1 expression levels.

2. Renal Cell Carcinoma: Novel Immunotherapy
Approaches
Sergio Bracarda, MD
San Donato Hospital
Arezzo, Italy
Exploring New Advancements in Immuno-Oncology Research:
Melanoma, Lung Cancer, and Renal Cell Carcinoma

3. Role of the Immune System in RCC Treatment
• Observations of immune-related spontaneous remissions3
• Several immune escape mechanisms reported4,5
• Historical SOC: Immunotherapy with interleukin-2 or
interferon-alfa3
• Documented alterations in various immune cell types5-8
• Identification of large numbers of tumor-infiltrating
lymphocytes9
3
RCC=renal cell carcinoma; SOC=standard of care; Treg=regulatory T cell.
1. Ascierto PA et al. J Trans Med. 2014;12:141. doi: 10.1186/1479-5876-12-141. 2. Eggermont A et al. OncoImmunology. 2014;3(1):e27560. 3. Escudier B. Ann Oncol. 2012;23(Suppl
8):viii35-viii40. 4. Noessner E et al. OncoImmunology. 2012;1(8):1451-1453. 5. Bockorny B et al. Expert Opin Biol Ther. 2013;13(6):911-925. 6. Hotta K et al. Br J Cancer.
2011;105(8):1191-1196. 7. Nakano O et al. Cancer Res. 2001;61(13):5132-5136. 8. Igarashi T et al. Urol Int. 2002;69(1):51-56. 9. Tripathi A et al. BioDrugs. 2014;28(6):513-526.
I-O is an evolving treatment modality encompassing agents designed to directly harness the
patient’s own immune system to fight cancer1,2
Tregs
CD45+
Memory T Cells
CD8+
T Cells
CD4+
T Cells
 levels:
unfavorable
prognosis
 levels:
unfavorable
prognosis
Favorable/
unfavorable
prognosis or
no association
 levels:
favorable/
unfavorable
prognosis

4. Rationale for Targeting the PD-1 Pathway in RCC
4
* 306 samples were analyzed by IHC; threshold was ≥5% tumor cells with membranous staining.
ccRCC=clear cell RCC; PD-1=programmed death-1; PD-L1=programmed death ligand 1; RCC=renal cell carcinoma.
1. Tripathi A et al. BioDrugs. 2014;28(6):513-526. 2. Harshman LC et al. Cancer Immunol Res. 2014;2(12):1132-1141. 3. Thompson RH et al. Cancer Res. 2006;66(7):3381-3385. 4.
Thompson RH et al. Clin Cancer Res. 2007;13(6):1757-1761. 5. Kang MJ et al. Transl Oncol. 2013;6(3):282-289.
Tumor cells (PD-L1)
• In RCC, increased PD-L1
expression has been shown to
be associated with worse
prognosis1,2
• 24% of ccRCC samples were
shown to express PD-L1*3
TILs (PD-1)
• High PD-1 expression on
tumor-infiltrating
lymphocytes has also
been associated with
distant metastatic relapse
and poor survival4,5
Blocking the PD-1/PD-L1 interaction can overcome immune evasion
and increase antitumor immunity3
Tumor
microenvironment

5. 1. Abe H et al. Int J Urol. 2013;20(10):944-955. 2. Figlin R et al. J Urol. 2012;188(3):707-715. 3. Hutson TE. Oncologist. 2011;16(suppl 2):14-22.
4. INLYTA [package insert]. New York, NY: Pfizer Labs; 2014. 5. Rini B et al. Lancet. 2011;378(9807):1931-1939. 6. Motzer RJ et al. J Clin Oncol. 2009;27(22):3584-3590. 7. Singer EA et
al. Curr Opin Oncol. 2011;23(3):283-289. 8. Calvani N et al. Med Oncol. 2013;30(2):578. 9. Small AC et al. Cancer. 2012;118(23): 5947-5954.
• Transient efficacy despite availability of targeted agents1
– 5-year survival rates for advanced disease is 23%2
• 7 approved targeted agents, but with only 2 distinct MOAs3,4
• Goal: improve outcomes beyond PFS extension2
Efficacy
• Targeted therapies can be associated with significant toxicities
– Discontinuation due to AEs: 4%–19%1,5,6
• Due to impaired tolerability, combination studies to date have been largely unsuccessful1,7
Toxicity
• Lack of consensus for optimal treatment sequencing of existing therapies8
• High rate of untreated metastatic patients
– 25.5% of patients presenting with stage IV disease receive no anticancer therapies9
Treatment
Algorithm
Key Clinical Unmet Needs in Advanced/Metastatic RCC Treatment
5

6. Trial Design Trial Name Dose ORR mPFS Median OS
Nivolumab
Phase 1
CA209-0031
NCT00730639
(N=34*)
1 or 10 mg/kg q2w 29% 7.3 mo 22.4 mo
Nivolumab
Phase 2
CA209-0102,3
NCT01354431
(N=168)
0.3, 2, or
10 mg/kg q3w
20%–22%† 2.7–4.2 mo† 18.5–25.5 mo†
Atezolizumab
Phase 1a
PCD4989g4,5
NCT01375842
(N=62)
10, 15, or
20 mg/kg q3w
15% 24 weeks -
Nivolumab vs everolimus
Phase 3
CheckMate 0256
NCT01668784
(N=821)
3mg/kg q2w
(for nivolumab)
25% vs 5%‡ 4.6 mo vs
4.4 mo
25.0 mo vs
19.6 mo‡
Summary of Data in Previously Treated Advanced/Metastatic RCC
• Consistent OS has been observed with nivolumab across multiple RCC trials1,2,6
• CheckMate 025 demonstrated superior OS over everolimus6
6
mRCC=metastatic renal cell carcinoma; ORR=objective response rate; mOS=median OS; mPFS=median progression-free survival; OS=overall survival.
1. McDermott DF et al. J Clin Oncol. 2015;33(18):2013-2020. 2. Plimack ER et al. Poster presentation at ASCO 2015. 4553. 3. Motzer RJ et al. Oral presentation at ASCO 2014. 5009. 4.
Cho D et al. Oral presentation at ASCO 2013. 4505. 5. McDermott DF et al. Oral presentation at ESMO 2014. 809O. 6. Sharma P et al. Oral presentation at ESMO 2015. 3LBA.
* In RCC cohort; † Across doses; ‡ Statistically significant.

7. CheckMate 025: Phase 3 Study of Nivolumab vs Everolimus in mRCC Patients
Who Have Received 1 or 2 Prior Anti-Angiogenic Therapies
Until
progression* or
intolerable
toxicity
7
N=821
Previously treated mRCC
Stratification factors
• Region
• MSKCC risk group
• Number of prior anti-
angiogenic therapies
Nivolumab
3 mg/kg intravenously
every two weeks
Everolimus
10 mg orally
once daily
Randomize1:1
* Treatment beyond progression was permitted if drug was well-tolerated and clinical benefit was noted.
mRCC=metastatic RCC; MSKCC=Memorial Sloan-Kettering Cancer Center; OS=overall survival; RCC=renal cell carcinoma.
Motzer RJ et al. N Engl J Med. 2015;373(19):1803-1813. Sharma P et al. Oral presentation at ESMO 2015. 3LBA.
Majority of mRCC therapies previously approved based on PFS primary endpoint
• Primary Endpoint: OS
• Secondary Endpoints: ORR, PFS, safety, QoL, OS by tumor expression of PD-L1

8. CheckMate 025: Progression-Free Survival
• In a post-hoc analysis of patients who had not progressed or died at 6 months, median PFS was 15.6 months for nivolumab vs
11.7 months for everolimus (HR [95% CI]: 0.64 [0.47–0.88])
• 44% of patients in the nivolumab arm and 46% of patients in the everolimus arm were treated beyond progression*
8
Median PFS, months (95% CI)
Nivolumab 4.6 (3.7–5.4)
Everolimus 4.4 (3.7–5.5)
No. of patients at risk
Nivolumab 410 230 145 116 81 66 48 29 11 4 0
Everolimus 411 227 129 97 61 47 25 16 3 0 0
HR (95% CI): 0.88 (0.75–1.03)
P = 0.1135
Months
Progression-Free
Survival(Probability)
Nivolumab
Everolimus
0 3 6 129 15 18 21 24 27 30
0.0
0.3
0.1
0.2
0.4
0.5
0.6
0.7
0.8
0.9
1.0
Figure adapted from Motzer et al.
* Treatment beyond progression was permitted if drug was well-tolerated and clinical benefit was noted.
CI=confidence interval; HR=hazard ratio; PFS=progression free survival; RECIST=response evaluation criteria in solid tumors.
Motzer RJ et al. N Engl J Med. 2015;373(19):1803-1813. Sharma P et al. Oral presentation at ESMO 2015. 3LBA.

9. CheckMate 025: Improved Overall Survival Versus Everolimus in mRCC
After 1 or 2 Prior Anti-Angiogenic Therapies
Median OS, months (95% CI)
Nivolumab (n=410) 25.0 (21.8–NE)
Everolimus (n=411) 19.6 (17.6–23.1)
HR=0.73 (98.5% CI, 0.57, 0.93); P=0.002
Nivolumab
0 3 6 129 15
Months
18 21 24 27 30 33
Number of Patients at Risk
Nivolumab 410 389 359 337 305 275 213 139 73 29 3 0
411 366 324 287 265 241 187 115 61 20 2 0Everolimus
0.0
0.3
0.1
0.2
0.4
0.5
0.6
0.7
0.8
0.9
1.0
OverallSurvival(Probability)
Everolimus
Figure adapted from Motzer et al.
Minimum follow-up was 14 months.
CI=confidence interval; HR=hazard ratio; NE=not estimable; OS=overall survival; RCC=renal cell carcinoma.
Motzer RJ et al. N Engl J Med. 2015;373(19):1803-1813.
9

10. Analyses based on interactive voice response system data.
MSKCC=Memorial Sloan Kettering Cancer Center.
Motzer RJ et al. N Engl J Med. 2015;373(19):1803-1813.
Sharma P et al. Oral presentation at ESMO 2015. 3LBA.
CheckMate 025: Improved Overall Survival Irrespective of MSKCC Risk Score,
Number of Previous Anti-Angiogenic Therapies, Region, or Gender
10
Subgroup Nivolumab
n/N
Everolimus
n/N
MSKCC risk group
Favorable 45/145 52/148
Intermediate 101/201 116/203
Poor 37/64 47/60
Prior anti-angiogenic regimens
1 128/294 158/297
2 55/116 57/114
Region
US/Canada 66/174 87/172
Western Europe 78/140 84/141
Rest of the world 39/96 44/98
Age, years
<65 111/257 118/240
≥65 to <75 53/119 77/131
≥75 19/34 20/40
Sex
Female 48/95 56/107
Male 135/315 159/304
Nivolumab
0.25 0.5 0.75 1.5 2.251
Everolimus
FavorsFigure adapted from Motzer et al.
OS Hazard Ratios

11. CheckMate 025: Survival Benefit With Nivolumab Is Independent
of PD-L1 Expression
11
PD-L1 <1% (n = 76%)
Median OS, months (95% CI)
Nivolumab 21.8 (16.5–28.1)
Everolimus 18.8 (11.9–19.9)
PD-L1 ≥1% (n = 24%)
Median OS, months (95% CI)
Nivolumab 27.4 (21.4–NE)
Everolimus 21.2 (17.7–26.2)
No. of patients at risk
Nivolumab 94 86 79 73 66 58 45 31 18 4 1 0
Everolimus 87 77 68 59 52 47 40 19 9 4 1 0
Months
OverallSurvival(Probability)
Nivolumab
Everolimus
276 265 245 233 210 189 145 94 48 22 2 0
299 267 238 214 200 182 137 92 51 16 1 0
Nivolumab
Months
0.0
0 3 6 129 15 18 21 24 27 30 33
0.3
0.1
0.2
0.4
0.5
0.6
0.7
0.8
0.9
1.0
0 3 6 129 15 18 21 24 27 30 33
0.3
0.1
0.2
0.4
0.5
0.6
0.7
0.8
0.9
1.0
0.0
Everolimus
HR (95% CI): 0.79 (0.53–1.17) HR (95% CI): 0.77 (0.60–0.97)
Figure adapted from Motzer et al.
CI=confidence interval; HR=hazard ratio; PD-L1=prgrammed death ligand 1.
Motzer RJ et al. N Engl J Med. 2015;373(19):1803-1813. Sharma P et al. Oral presentation at ESMO 2015. 3LBA.

12. CheckMate 025: Antitumor Activity
12
Nivolumab
N = 410
Everolimus
N = 411
Objective response rate, % 25% 5%
Odds ratio (95% CI)
P value
5.98 (3.68–9.72)
<0.0001
Best overall response, %
Complete response
Partial response
Stable disease
Progressive disease
Not evaluated
1%
24%
34%
35%
6%
1%
5%
55%
28%
12%
Median time to response, months (range) 3.5 (1.4–24.8) 3.7 (1.5–11.2)
Median duration of response, months (range)* 12.0 (0–27.6) 12.0 (0–22.2)
Ongoing response, n/N (%) 49/103 (48%) 10/22 (45%)
Remains on treatment/received treatment, n/n (%) 67/406 (17%) 28/397 (7%)
* For patients without progression or death, duration of response is defined as the time from the first response (CR/PR) date to the date of censoring.
CI=confidence interval.
Motzer RJ et al. N Engl J Med. 2015;373(19):1803-1813.

13. CheckMate 025: Duration of Response
13
Responders
Time (Weeks)
0 16 32 6448 80 96 112 128
• The minimum follow-up was 14 months
• The majority of patients showed a
response at first assessment
Figure adapted from Motzer et al.
Motzer RJ et al. N Engl J Med. 2015;373(19):1803-1813.
Ongoing response
First response
Off treatment
Nivolumab
Everolimus
On treatment

14. CheckMate 025: Significant and Consistent Improvement in Quality of Life
With Nivolumab
14
Nivolumab
Everolimus
FKSI-DRS:MeanChange
FromBaseline
Week
40 8 12 16 20 24 28 32 36 40 44 48 52 56 60 64 68 72 76 80 84 88 92 96 100 104
-6
0
-4
-2
2
4
6
BetterWorse
Figure adapted from Motzer et al.
• Mean change from baseline in the FKSI-DRS* score in the nivolumab group increased over time and
differed significantly from the everolimus group at each assessment through Week 104 (P<0.05)
Questionnaire completion rate: ≥80% during the first year of follow-up.
* The FKSI-DRS questionnaire consists of nine symptom-specific questions that address lack of energy, pain, weight loss, bone pain, fatigue, dyspnea, cough, fevers, and hematuria.
FKSI-DRS=Functional Assessment of Cancer Therapy Kidney Symptom Index–Disease-Related Symptoms; QoL=quality of life.
Motzer RJ et al. N Engl J Med. 2015;373(19):1803-1813. Sharma P et al. Oral presentation at ESMO 2015. 3LBA.

15. CheckMate 025: Safety Summary
15
Nivolumab
N = 406
Everolimus
N = 397
Any
Grade
Grade
3-4
Any
Grade
Grade
3-4
Treatment-related AEs, % 79 19 88 37
Treatment-related AEs leading to
discontinuation, %
8 5 13 7
Treatment-related deaths, n 0 2*
Nivolumab was associated with fewer Grade 3 and 4 treatment-related AEs and fewer
treatment-related AEs leading to discontinuation than everolimus
AE=adverse event.
Motzer RJ et al. N Engl J Med. 2015;373(19):1803-1813. Sharma P et al. Oral presentation at ESMO 2015. 3LBA.
* Septic shock (1), bowel ischemia (1).

16. CheckMate 025: Treatment-Related AEs in ≥10% of Patients
16
Nivolumab
N = 406
Everolimus
N = 397
Any grade Grade 3 Grade 4* Any grade Grade 3 Grade 4†
Treatment-related AEs, % 79 18 1 88 33 4
Fatigue 33 2 0 34 3 0
Nausea 14 <1 0 17 1 0
Pruritus 14 0 0 10 0 0
Diarrhea 12 1 0 21 1 0
Decreased appetite 12 <1 0 21 1 0
Rash 10 <1 0 20 1 0
Cough 9 0 0 19 0 0
Anemia 8 2 0 24 8 <1
Dyspnea 7 1 0 13 <1 0
Edema, peripheral 4 0 0 14 <1 0
Pneumonitis 4 1 <1 15 3 0
Mucosal inflammation 3 0 0 19 3 0
Dysgeusia 3 0 0 13 0 0
Hyperglycemia 2 1 <1 12 3 <1
Stomatitis 2 0 0 29 4 0
Hypertriglyceridemia 1 0 0 16 4 1
Epistaxis 1 0 0 10 0 0
* Grade 4 AEs not listed in table: increased blood creatinine (1), acute kidney injury (1), anaphylactic reaction (1). † Grade 4 AEs not listed in table: increased blood triglycerides (2), acute
kidney injury (1), sepsis (1), chronic obstructive pulmonary disorder (1), increased blood cholesterol (1), neutropenia (1), pneumonia (1).
AE=adverse event.
Motzer RJ et al. N Engl J Med. 2015;373(19):1803-1813. Sharma P et al. Oral presentation at ESMO 2015. 3LBA.

17. Rationale for Combining I-O Therapies With Targeted Agents
or Other I-O Therapies
17
IFN-γ=interferon-gamma; I-O=immuno-oncology; MDSC=myeloid-derived suppressor cell; mRCC=metastatic RCC; RCC=renal cell carcinoma; Treg=regulatory T cell; VEGF=vascular
endothelial growth factor; VEGFR=VEGF receptor.
1. Motz GT, Coukos G. Nat Rev Immunol. 2011;11(10):702-711. 2. Adotevi O, et al. J Immunother. 2010;33(9):991-998. 3. Heine A et al. Leukemia. 2011;25(6):899-905. 4. Busse A, et al.
Eur J Cancer. 2011;47(5):690-696. 5. Sharpe K et al. Clin Cancer Res. 2013;19(24):6924-6934. 6. Elamin YY et al. Cancer Microenviron. 2015;8:15-21. 7. Drake C. Ann Oncol.
2012(suppl 8):viii41-viii46.
Agents that target the VEGF pathway
may regulate immune components such as1-6:
T cells Tregs MDSCs PD-L1
Combination of immunotherapies can target multiple
pathways and may have synergistic effects7
RCC tumor
microenvironment
VEGF inhibition may mediate immune infiltration through direct effects
on the tumor vasculature, making the combination of checkpoint inhibition and
VEGF blockade a promising approach

18. Summary of Early Phase Combination Data in Advanced/Metastatic RCC
* Not including nivolumab 3 mg/kg + ipilimumab 3 mg/kg arm (n=6), in which there were no responses; † Trial also enrolling 1L+ melanoma patients; ‡ For RCC cohort;
§ Part II of trial will randomize patients to pembrolizumab + pazopanib vs pembrolizumab vs pazopanib; ║ Across doses.
IFN=interferon; L=line; mOS=median overall survival; mPFS=median progression-free survival; NA=not available; NR=not reached; ORR=objective response rate.
1. Hammers H et al. Poster presentation at ASCO 2015. 4516. 2. Amin A et al. Oral presentation at ASCO 2014. 5010. 3. Clinicaltrials.gov. NCT02089685.
4. Atkins MB et al. Poster presentation at ASCO 2015. 3009. 5. Sznol M et al. Poster presentation at ASCO GU 2015. 410.
6. McDermott DF et al. Poster presented at ESMO 2015. Abstract 2622. 7. Clinicaltrials.gov. NCT02014636.
Trial Design Trial Name Patient Population ORR mPFS mOS
Nivolumab +
• ipilimumab
• sunitinib
• Pazopanib
Phase 1
CheckMate 0161,2
NCT01472081
• (N=94)
• (N=33)
• (N=20)
1L+
• 38%–40%*
• 52%
• 45%
• 33.3–47.1 wks
• 48.9 wks
• 31.4 wks
NR
Pembrolizumab +
• peg-IFN
• Ipilimumab
Phase 1/2
KEYNOTE-0293,4
NCT02089685†
(N=10‡)
2L+‡ • NA
• 3 partial responses
NA NA
Atezolizumab +
bevacizumab
Phase 1
NCT016339705
(N=10‡)
1L+ 40% NA NA
Pembrolizumab +
pazopanib§
Phase 1/2
NCT020146366,7
(N=20)
1L 20%–60%║ NA NA
18

19. Trial Design Trial Name Patient Population 1° Endpoint Data Available
Nivolumab + ipilimumab vs
sunitinib
Phase 3
CheckMate 2141
NCT02231749
(N=1070)
1L
PFS and OS in intermediate-
and poor-risk patients
November 2017
Pembrolizumab + axitinib
Phase 1
NCT021337422
(N=60)
1L DLTs March 2017
Pembrolizumab + bevacizumab
Phase 1/2
NCT023480083
(N=61)
1L+
Maximum safe dose,
response rates
March 2017
Atezolizumab +
IFN-α2b†
Phase 1
NCT021741724
(N=200*)
1L+ solid tumors,
including RCC
DLTs, AEs February 2018
Atezolizumab +
bevacizumab vs sunitinib
Phase 3
IMmotion1515
NCT02420821
(N=550)
1L PFS February 2019
Avelumab + axitinib
Phase 1
NCT024937516
(N=55)
1L DLTs March 2018
* In all cohorts; † Trial also has an atezolizumab + ipilimumab arm enrolling NSCLC patients only.
AE=adverse event; DLT=dose-limiting toxicity; IFN=interferon; L, line; NSCLC=non-small cell lung cancer; ORR=objective response rate; OS=overall survival; PFS=progression-free survival;
Ph=phase; RCC=renal cell carcinoma; VEGF=vascular endothelial growth factor.
1. Clinicaltrials.gov. NCT02231749. 2. Clinicaltrials.gov. NCT02133742. 3. Clinicaltrials.gov. NCT02348008. 4. Clinicaltrials.gov. NCT02174172.
5. Clinicaltrials.gov. NCT02420821. 6. Clinicaltrials.gov. NCT02493751.
Select Additional Ongoing Combination Trials in Advanced/Metastatic RCC
19

20. Understanding Immune-Related Toxicities
Immuno-Oncology3mTOR Inhibitors1
• Fatigue, asthenia, pain
• Infection
• Stomatitis
• GI toxicities
• Dyspnea, cough
• Pneumonitis
• Rash
• Hematological and lab abnormalities
VEGF-Targeted Therapies2
• Fatigue, asthenia
• Hypertension
• GI toxicities
• Hand-foot syndrome and other skin
toxicities
• Hematological and lab abnormalities
• Hepatotoxicity
Headache
Hypophysitis
Dermatitis
Rash
Pruritus
Pneumonitis
Liver enzyme elevation
Colitis
Diarrhea
Nausea
Fatigue
Infusion reactions
GI=gastrointestinal; mTOR=mammalian target of rapamycin; VEGF=vascular endothelial growth factor.
1. Ravaud A. Oncologist. 2011;16(suppl 2):32-44. 2. Mendez-Vidal MJ et al. Cancer Metastasis Review. 2012;31(suppl 1):S19-S27.
3. Gangadhar TC, Vonderheide RH. Nat Rev Clin Oncol. 2014;11(2):91-99.
20

21. Potential Biomarkers Under Investigation in RCC
Pharmacodynamic Biomarkers1-5 Predictive Biomarkers1-5
• Tumor T-cell infiltrates at baseline and on
treatment
• Gene expression profiles (tumor and peripheral
blood)
• Serum biomarkers
• Antitumor antibodies
• PD-L1
• Tumor T-cell infiltrates
• Tumor gene expression profiles
• Peripheral blood gene expression profiles
• Serum soluble factors
• TCR repertoire
PD-L1=programmed death ligand-1; RCC=renal cell carcinoma; TCR=T-cell receptor.
1. Clinicaltrials.gov. NCT01358721. 2. Choueiri TK et al. Oral presentation at ASCO 2014. 5012. 3. Choueiri TK et al. Poster presentation at ESMO 2014. 1051PD.
4. Choueiri TK et al. Poster presentation at AACR 2015. 1306. 5. Choueiri TK et al. Oral presentation at ASCO 2015. 4500.
21

22. Clinical Data Reveals Benefit of PD-1/L1 Inhibition is Independent
of PD-L1 Status
22
HR=hazard ratio; IHC=immunohistochemistry; mDOR=median duration of response; mOS=median overall survival; mPFS=median progression-free survival; ORR=objective response
rate; PD-L1=programmed death ligand-1.
1. Sharma P et al. Oral presentation at ESMO 2015. 3LBA. 2. Motzer RJ et al. N Engl J Med. 2015;373(19):1803-1813. 3. McDermott DF et al. Oral presentation at ESMO 2014. 809O.
Phase 3 CheckMate 025 (Nivolumab vs Everolimus)1,2
Phase 1 PCD4989 (Atezolizumab Trial)3
PD-L1 IHC n/N (%) ORR mDOR mPFS
Overall (N=62) 15% 76 weeks 24 weeks
IHC 1/2/3 (≥1% PD-L1) 35/62 (56%)† 20% 54 weeks 24 weeks
IHC 0 (<1% PD-L1) 21/62 (34%)† 10% NR 20 weeks
Nivolumab and atezolizumab demonstrated efficacy regardless of PD-L1 status
PD-L1 IHC (N=756*) n/N (%) mOS (Nivolumab vs Everolimus)
≥1% PD-L1 181/756 (24%) 21.8 months vs 18.8 months, HR=0.79
<1% PD-L1 575/756 (76%) 27.4 months vs 21.2 months, HR=0.77
* Of the 821 randomized patients, 756 patients had quantifiable tumor PD-L1 expression – 90% in nivolumab group and 94% in the everolimus group.
† 6 patients had unknown PD-L1 IHC status.
Overall mOS (Nivolumab vs Everolimus)
Overall (N=821*) 25.0 months vs 19.6 months, HR=0.73

23. Additional Immunotherapeutic Approaches Under Investigation
23
Vaccines1-3
AGS-003 (autologous DC vaccine)
IMA901 (multipeptide vaccine)
Trial Name Pt Population Trial Design 1° Endpoint Data/Conclusions
ADAPT (Ph III)1 NCT01582672
(N=450)
1L AGS-003 + sunitinib vs sunitinib OS Data available April 2016
IMPRINT (Ph III)2,3
NCT01265901 (N=339)
1L,
HLA-A*02+
IMA901 (+ GM-CSF + CY) + sunitinib
vs sunitinib
OS
• Trial completed
• 1° endpoint not reached
Oncolytic Viruses4
Pexa-Vec (vaccinia virus expressing GM-CSF)
Trial Pt Population Trial Design 1° Endpoint Data/Conclusions
Ph II4
(N=17)
2L+ Pexa-Vec Response
• RR = 6% (1 PR); Week 6 DCR = 76%
• mPFS = 12 weeks
• mOS = 10.5 months
• Further trials warranted
CY=cyclophosphamide; DC=dendritic cell; GM-CSF, granulocyte-macrophage colony-stimulating factor; HLA=human leukocyte antigen; L=line; mOS=median OS;
mPFS=median progression-free survival; OS= overall survival; TAA=tumor-associated antigen.
1. Clinicalrials.gov. NCT01582672. 2. Clinicaltrials.gov. NCT01265901. 3. Rini B et al. Oral presentation at ESMO 2015. 17LBA. 4. Kim SG et al. Poster presentation at ESMO
2015. 2597.
Tumor cells DCs
TAAs

24. Summary
• Current therapies used to treat metastatic/advanced RCC are associated with limited efficacy and
significant toxicity affecting tolerability and quality of life
• RCC is considered an immunogenic tumor type, supported by evidence of spontaneous remissions,
alterations in various immune cell types, and the historical use of cytokines
– This provides rationale for further development of immuno-oncology (I-O) agents in RCC
• Immune checkpoint inhibitors have shown an interesting signal of activity in RCC, mostly in
previously treated patients*
– Either as monotherapy or in combination with other agents
– Novel phase 3 results in previously treated patients demonstrate improved overall survival,
objective response rate, and quality of life with I-O therapy versus current standard of care in
pretreated patients*
• The clinical relevance of different biomarkers is being investigated in RCC
24
* Phase 3 1L data is not yet available in RCC.
RCC=renal cell carcinoma.