1. Clinical Application of Immune Checkpoint Inhibitors in Bladder Cancer
This program is supported by educational grants from Genentech and Merck.

2. Clinical Development of Immune Checkpoint Inhibitors: Quiz Round 2
Jonathan E. Rosenberg, MD Associate Attending Physician  Genitourinary Oncology Service Division of Solid Tumor Oncology Department of Medicine Memorial Sloan Kettering Cancer Center New York, New York
This program is supported by educational grants from Genentech and Merck.

3. About These Slides
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Disclaimer: The materials published on the Clinical Care Options Web site reflect the views of the authors of the CCO material, not those of Clinical Care Options, LLC, the CME providers, or the companies providing educational grants. The materials may discuss uses and dosages for therapeutic products that have not been approved by the United States Food and Drug Administration. A qualified healthcare professional should be consulted before using any therapeutic product discussed. Readers should verify all information and data before treating patients or using any therapies described in these materials.

4. Faculty Program Director:
Daniel P. Petrylak, MD Professor of Medicine
Medical Oncology
Director, Prostate and GU Medical Oncology
Director, Prostate Cancer Translational Research Group
Yale Cancer Center
New Haven, Connecticut
Elizabeth R. Plimack, MD, MS Director, Genitourinary Clinical Research Associate Professor, Department of Hematology/Oncology Fox Chase Cancer Center Temple Health Philadelphia, Pennsylvania
David I. Quinn, MBBS, PhD, FRACP, FACP Associate Professor of Medicine Division of Cancer Medicine and Blood Diseases The University of Southern California Medical Director USC Norris Cancer Hospital and Clinics Los Angeles, California Jonathan E. Rosenberg, MD Associate Attending Physician Genitourinary Oncology Service Division of Solid Tumor Oncology Department of Medicine Memorial Sloan Kettering Cancer Center New York, New York
This slide lists the faculty who were involved in the production of these slides.

5. Faculty Disclosures
Daniel P. Petrylak, MD, has disclosed that he has received consulting fees from Bayer, Bellicum, Dendreon, Exelixis, Ferring, Johnson & Johnson, Medivation, Millennium, Pfizer, Roche Laboratories, sanofi-aventis, and Tyme; has received funds for research support from Agensys, Celgene, Dendreon, Eli Lilly, Johnson & Johnson, Millennium, Oncogenex, Progenics, sanofi- aventis; and has ownership interest in Bellicum and Tyme. Elizabeth R. Plimack, MD, MS, has disclosed that she has received consulting fees from Acceleron, Bristol-Myers Squibb, Genentech, Eli Lilly, Novartis, Pfizer, Roche, and Synergene and funds for research support from AstraZeneca, Bristol-Myers Squibb, and Merck.
This slide lists the disclosure information of the faculty and staff involved in the development of these slides.

6. Faculty Disclosures
David I. Quinn, MBBS, PhD, FRACP, FACP, has disclosed that he has received consulting fees from Astellas, AstraZeneca, Bayer, Exelixis, Genentech, Merck, Novartis, Peloton, Pfizer, Sanofi, Serono, and Vertex. Jonathan E. Rosenberg, MD, has disclosed that he has intellectual property rights/patents from Somatic ERCC2 mutation and platinum sensitivity; has received consulting fees from Agensys, Eli Lilly, Genentech/Roche, OncoGeneX, and sanofi- aventis; and has ownership interest in Illumina and Merck.
This slide lists the disclosure information of the faculty and staff involved in the development of these slides.

7. Outline
Efficacy of PD-1 and PD-L1 inhibitors in advanced bladder cancers
Insights into efficacy and pt response
Biomarkers for pt selection
Therapeutic strategies to enhance an antitumor immune response for bladder cancer
Ongoing investigation of immunotherapies in advanced bladder cancer
Single-agent therapy
Combinations
Slide credit: clinicaloptions.com

8. Bladder Cancer: Overview
5th most common cancer, 4th among men
2016: estimated 76,960 new cases in US with estimated 16,390 deaths; 2.4% lifetime risk
No change in treatment outcomes in more than 30 yrs!
No FDA-approved treatments following platinum therapy until atezolizumab approval in May 25
New Cases
Pt Surviving 5 Yrs
77.5% 20 15
Number per 100,000 Persons 10 5
Deaths
1992
1995
1998
2001
2004
2007
2010
2013 Yr
Slide credit: clinicaloptions.com
SEER Stat fact sheets: bladder cancer.

9. Rationale for Targeting PD-1 and PD-L1 in Bladder Cancer
3rd highest mutational burden after lung cancer and melanoma
High prevalence of nonsynonymous mutations in bladder cancer, possibly leading to higher neoantigen load
History of immunotherapy with BCG for non-muscle- invasive bladder cancer dates back > 30 years
Slide credit: clinicaloptions.com
Alexandrov LB, et al. Nature. 2013;500:

10. PD-1/PD-L1 Inhibition in Urothelial Cancer: Atezolizumab, Pembrolizumab
Atezolizumab: PD-L1 inhibitor
All pts, regardless of PD-L1 status
Urothelial carcinoma (approved)
TNBC
Melanoma
NSCLC
RCC
Other tumor types
Pembrolizumab: PD-1 inhibitor
Pts with PD-L1 positivity (> 1% of cells)
Urothelial carcinoma
TNBC
Gastric/CRC cancer
Head and neck cancer
Melanoma (approved)
NSCLC (approved for PD-L1+)
CRC, colorectal cancer; NCSCL, non-small-cell lung cancer; RCC, renal cell carcinoma; TNBC, triple-negative breast cancer.
Slide credit: clinicaloptions.com

11. Atezolizumab, Pembrolizumab, Avelumab: Promising Activity in Adv UC
Pembrolizumab (Anti–PD-1)[1]
100
Atezolizumab (Anti–PD-L1)[2]
100 80
IC0
IC1
IC2
IC3 80
CR PR SD PD 60 60
64% experienced a decrease in target lesions 40 40 20 20
Change From Baseline in Sum of Longest Diameter of Target Lesion (%)
-20
-20
-40
-40
30% decrease
-60
-60
-80
-80
-100
-100
CR PR SD PD Not evaluable Visceral metastasis (site of target metastatic lesions noted) Nodal or soft tissue metastasis
100
Pts with UC (N = 40)* 80 60 40
Adv, advanced; IC, immune cell; PD, progressive disease; SD, stable disease; UC, urothelial carcinoma. 20
Avelumab
(Anti–PD-L1)[3]
Change From Baseline in Sum of Target Lesion Diameter (%)
-20
-40
30% decrease
-60
Stomach
Liver
Soft tissue
-80
-100
Peritoneum and sigmoid mesentery
1. Plimack ER, et al. ASCO Abstract Powles T, et al. Nature. 2014;515: Apolo AB, et al. ASCO GU Abstract 367.
Lung
Slide credit: clinicaloptions.com

12. Durvalumab (PD-L1) and Nivolumab (PD-1): Promising Activity in Advanced UC
To be presented at ASCO 2016 on Sunday, June 5, at 8 AM in Hall D2
Phase I/II Dose Escalation and Expansion Study of Durvalumab in Advanced or Metastatic UBC[1]
Phase I/II Study of Nivolumab in Metastatic UC after Failure of Platinum-Based Chemotherapy[2]
PD-L1 Expression by Location
PD-L1 Status
ORR, n/N (%) TC
Any
16/42 (38.1) +
8/15 (53.3) -
8/27 (29.6) IC
11/18 (61.1)
5/24 (20.8)
TC or IC
15/28 (53.6)
1/14 (7.1)
Parameter
Nivolumab
(N = 78)
ORR, %
24.4
Median PFS, mos
2.8
Median OS, mos NE
12-mo OS rate, %
51.6
Median TTR, mos
1.5
Median DOR, mos
DOR, duration of response; IC, immune cell; NE, not estimable; TC, tumor cell; TTR, time to response; UC, urothelial carcinoma; UBC, urothelial bladder cancer.
Note: These data are from the abstracts and may be slightly different in the oral presentations, which were not yet available at the time of this symposium.
1. Massard C, et al. ASCO Abstract Sharma P, et al. ASCO Abstract 4501.
Slide credit: clinicaloptions.com

13. Pembrolizumab in Urothelial Cancer (KEYNOTE-012 Cohort): Responses
Pembrolizumab: anti–PD-1 antibody approved for metastatic melanoma and PD-L1–positive NSCLC
Response
Patients Evaluable for Response* (N = 29) n %
95% CI
ORR 8
27.6
Best overall response CR 3
10.3 PR 5
17.2
Stable response
Progressive disease 14
48.3
Disease control rate 11
37.9
No assessment 4
13.8
NSCLC, non-small-cell lung cancer.
Slide credit: clinicaloptions.com
Plimack ER, et al. ASCO Abstract 4502.

14. Pembrolizumab in Urothelial Cancer (KEYNOTE-012 Cohort): PFS, OS
PFS (n = 29)
OS (n = 29)
100
100 90 90 80 80 70 70 60 60
PFS (%) 50
OS (*%) 50 40 40 30 30 20 20 10 10
NR, not reached. 2 4 6 8 10 12 14 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18
Mos
Mos
Median PFS: 2 mos (95% CI: )
PFS rate at 12 mos: 19.1%
Median OS: 12.7 mos (95% CI: NR)
OS rate at 12 mos: 52.9%
Slide credit: clinicaloptions.com
Plimack ER, et al. ASCO Abstract 4502.

15. Phase II IMvigor210 at ASCO 2016: Atezolizumab in Urothelial Carcinoma
2-cohort study in metastatic or locally advanced urothelial carcinoma
Cohort 1: no chemotherapy for metastatic disease[1]
Data to be presented on 6/5/2016 at 8 AM in Hall D2
Cohort 2: prior platinum-based chemotherapy (N = 310)[2-4]
Multiple abstracts to be presented based on this cohort
Atezolizumab FDA approved in May 2016 for the treatment of locally advanced or metastatic urothelial carcinoma with progression during or following platinum chemotherapy
1. Balar AV, et al. ASCO Abstract LBA4500.
2. Dreicer R, et al. ASCO Abstract Rosenberg JE, et al. Lancet. 2016;[Epub ahead of print]. 4. Rosenberg JE, et al. ASCO Abstract 104.
Slide credit: clinicaloptions.com

16. Phase II IMvigor210 at ASCO 2016: Atezolizumab in Urothelial Carcinoma
Single-arm phase II study with 2 cohorts[1]
Pts with inoperable advanced or metastatic UC, predominantly TCC histology, evaluable tumor tissue for PD-L1 testing
(N = 429)
Cohort 1: (N = 119)[2]
previously untreated,
Cisplatin ineligible*
Atezolizumab
1200 mg IV Q3W
until PD
Cohort 2: (N = 310)[3,4]
prior platinum
treatment
Atezolizumab
1200 mg IV Q3W
until loss of benefit
Primary endpoints:
Cohort 1: confirmed ORR by RECIST v1.1 (per central, independent review)
Cohort 2: confirmed ORR by RECIST v1.1 (per central review), ORR per immune-modified RECIST (per investigator)
DOR, duration of response; ECOG PS, Eastern Cooperative Oncology Group; eGFRCG, estimated Glomerular Filtration Rate Cockcroft-Gault; mUC, metastatic urothelial carcinoma; ORR, objective response rate; PD, progressive disease; PS, performance status; RECIST, Response Evaluation Criteria in Solid Tumors; TCC, transitional cell carcinoma.
1. ClinicalTrials.gov. NCT Balar AV, et al. ASCO Abstract LBA Dreicer R, et al. ASCO Abstract Rosenberg JE, et al. Lancet. 2016;387:
Slide credit: clinicaloptions.com

17. IMvigor210: Cohort 2 Pt Flowchart
Cohort 2: Locally advanced/metastatic UC with progression after platinum-based chemotherapy
Screened (n = 486)
Excluded (n = 170*)
Brain metastasis (n = 26)
ECOG PS 2 (n = 22)
Inadequate hematologic/end organ function (n = 18)
Life expectancy < 12 wks (n = 15)
Informed consent form not signed (n = 14)
No measurable disease (n = 13)
Other disease, metabolic dysfunction, or study drug contraindicated (n = 9)
Other (eg, autoimmune disease, prior therapy, abnormal laboratory results; n = 53)
Enrolled (n = 316)†
Received treatment (n = 311)†
Efficacy/safety evaluable (n = 310)‡
Still on therapy (n = 62)
Discontinued treatment (n = 248)
Progression of disease (n = 211)
Adverse event (n = 13)
Withdrawal by subject (n = 9)
Other (n = 15)
ECOG, Eastern Cooperative Oncology Group; PS, performance status; UC, urothelial carcinoma.
Data cutoff Sept 14, 2015
*Includes rescreened pts. †Excludes 1 pt with unknown site. ‡1 pt not evaluable because of incorrect cohort assignment.
Slide credit: clinicaloptions.com
Rosenberg JE, et al. Lancet. 2016;387:

18. IHC Status of Treated Pts in IMvigor210 Study (N = 311)
PD-L1 Expression on Immune Cells: Predictive Marker for Response to Atezolizumab
IHC Status of Treated Pts in IMvigor210 Study (N = 311)
IC2/3
≥ 5%
IC1
≥ 1 but < 5%
IC0
< 1%
PD-L1 staining on tumor cells and ICs hypothesized to be biomarker for activity of PD-1/PD-L1 therapy
Atezolizumab phase II trial: pts enrolled with any PD-L1 status
PD-L1 expression measured prospectively using companion diagnostic
IC1
35%
n = 108
IC2/3
32%
n = 100
IC, immune cell.
IC0
33%
n = 103
Slide credit: clinicaloptions.com
Rosenberg J, et al. European Cancer Congress Abstract 21LBA.

19. IMvigor210: Change in Tumor Burden by PD-L1 Subgroup*
100
‒100
ORR,† %
PD-L1 Status
Reduction in tumor burden associated with PD-L1 status
117/257 pts with tumor assessments (46%) had SLD reductions
52/85 (61)
IC2/3 26
100
‒100 *
Mean SLD Reduction From Baseline (%)
40/88 (45)
IC1 10 *
100
‒100
25/84 (30)
IC0 8
Response assessments†
IC, immune cell; PD, progressive disease; RECIST, Response Evaluation Criteria in Solid Tumors; SD, stable disease; SLD, sum of largest diameter; IRF, independent review facility.
PD SD PR CR Unknown
*> 100%. †Per IRF RECIST v1.1. Data cutoff: September 14, 2015.
Pts without postbaseline tumor assessments included those who discontinued before the first tumor assessment and are not plotted. Several pts with CR had < 100% reduction due to lymph node target lesions. All lymph nodes returned to normal size per RECIST v1.1.
Slide credit: clinicaloptions.com
Hoffman-Censits JH, et al. ASCO GU Abstract 355.

20. IMvigor210: Change in Tumor Burden Over Time With Atezolizumab
IC2/3: PR/CR (n = 26)
IC2/3: Stable Disease (n = 16)
IC2/3: Progressive Disease (n = 42)
100
New lesion Discontinued treatment > 100% 75 50 25
Change in Sum of Largest Diameters From Baseline (%)
-25
-50
-75
-100
IC, immune cell. 2 4 6 8 10 12 14 16 2 4 6 8 10 12 14 16 2 4 6 8 10 12 14 16
Mos
Mos
Mos
Durable responses noted
Atypical response kinetics seen, although rare
Slide credit: clinicaloptions.com
Rosenberg JE, et al. Lancet. 2016;387:

21. IMvigor210: PFS in Metastatic Urothelial Carcinoma
IC2/3 (n = 100)
IC0/1 (n = 210)
All (N = 310)
Per confirmed IRF RECIST v1.1
Median PFS, mos (95% CI)
2.1 ( )
2.1 ( )
2.1 ( )
6-mo PFS, %
(95% CI) 30
(21-39)
At risk: 30 17
(12-22)
At risk: 34
21 (17-26)
At risk: 64
Per investigator mRECIST
4.0 ( )
2.2 ( )
2.7 ( )
PFS per IRF RECIST v1.1
100 80 60
PFS (%) 40 20
– IC2/3
– IC0/1
IC, immune cell; RECIST, Response Evaluation Criteria in Solid Tumors; IRF, independent review facility. 2 4 6 8 10 12 14
Mos
Median follow-up: 11.7 mos (range: 0.2+ to 15.2) Data cutoff: September 14, 2015.
Slide credit: clinicaloptions.com
Hoffman-Censits JH, et al. ASCO GU Abstract 355.

22. IMvigor210: OS Associated With PD-L1 Expression on Immune Cells
100
Median OS, Mos (95% CI)
12-Mo OS, % (95% CI) 90
IC2/3 (n = 100) IC1 (n = 107) IC0 (n = 103)
11.4 (9.0-NE) 6.7 ( ) 6.5 ( )
48 (38-58) 30 (20-39) 29 (20-39) 80 70 60
OS (%) 50 40 30 20 10
Censored
IC, immune cell; NE, not estimable. 2 4 6 8 10 12 14 16
Mos
Pts at Risk, n IC2/3 IC1 IC0
2 1 1
Slide credit: clinicaloptions.com
Rosenberg JE, et al. Lancet. 2016;387:

23. IMvigor210: PD-L1 IC and TC Scores Associated With Basal Phenotype
IC Score by TCGA Subtype
TC Score by TCGA Subtype
IC0
IC1
IC2
IC3
TC0
TC1
TC2
TC3
n = 72
n = 50
n = 38
n = 35
n = 72
n = 50
n = 38
n = 35
100
100 75 75
Percentage 50
Percentage 50 25 25
IC, immune cell; TC, tumor cell; TCGA, The Cancer Genome Atlas
Cluster I
Cluster II
Cluster III
Cluster IV
Cluster I
Cluster II
Cluster III
Cluster IV
Luminal
Basal
Luminal
Basal
Slide credit: clinicaloptions.com
Rosenberg JE, et al. Lancet. 2016;387:

24. IMvigor210: Response to Atezolizumab Enriched in Luminal II Cluster
Response by TCGA Subtype PD SD PR CR
n = 72
n = 50
n = 38
n = 35
100 75
Percentage 50 25
PD, progressive disease; SD, stable disease; TCGA, The Cancer Genome Atlas.
Cluster I
Cluster II
Cluster III
Cluster IV
Luminal
Basal
Slide credit: clinicaloptions.com
Rosenberg JE, et al. Lancet. 2016;387:

25. IMvigor210: Mutation Load Associated with Objective Responses
TCGA, The Cancer Genome Atlas; SD, stable disease; PD, progressive disease.
No difference in responses based on TCGA Expression Subtype
These findings suggest that factors beyond PD-L1 are important in predicting response
Insights are important for new biomarker development
Slide credit: clinicaloptions.com
Rosenberg JE, et al. Lancet. 2016;387:

26. Phase Ib Study: Avelumab in Metastatic Urothelial Carcinoma (JAVELIN Cohort)
Avelumab: investigational anti–PD-L1 antibody
Clinical Activity Endpoint
Pts (N = 44)
CR, n (%)
1 (2.3)
PR, n (%)
6 (13.6)
SD, n (%)
19 (43.2)
PD, n (%)
14 (31.8)
Nonevaluable, n (%)*
4 (9.1)
ORR, % (95% CI)
15.9 ( )
DCR, %
59.0
Median PFS, wks (95% CI)
12.0 (7.3-NE)
DCR, disease control rate; NE, not estimable; PD, progressive disease; SD, stable disease.
*Missing and/or not assessable information
Slide credit: clinicaloptions.com
Apolo AB, et al. ASCO GU Abstract 367.

27. Avelumab in Metastatic Urothelial Carcinoma: Responses by PD-L1 Status
PD-L1 Expression Cutoff Level (n = 32)
ORR in PD-L1+, n/N1* (%) [95% CI]
ORR in PD-L1-, n/N1* (%) [95% CI]
≥ 1 % tumor cells
4/11 (36.4) [ ]
2/21 (9.5) [ ]
≥ 5% tumor cells
4/10 (40.0) [ ]
2/22 (9.1) [ ]
≥ 25% tumor cells
2/5 (40.0) [ ]
Neg 1: 2/22 (9.1) [ ]
Neg 2: 2/5 (40.0) [ ]
≥ 10% infiltrating immune cells
0/2 (0) [0-84.2]
6/30 (20.0) [ ]
Neg 1, negative threshold criteria 1; Neg 2, negative threshold criteria 2.
*N1 = # of pts with evaluable PD-L1 expression
Possible enrichment for response in specimens expressing PD-L1 on tumor cells
Slide credit: clinicaloptions.com
Apolo AB, et al. ASCO GU Abstract 367.

28. Pseudoprogression in Bladder Cancer
New liver lesions
No symptoms
Regression of many lesions
Baseline scan
After 3 cycles of therapy
6 months later
7% in IMvigor210
Slide credit: clinicaloptions.com
Rosenberg JE, et al. Lancet. 2016;387:

29. Current Status of Immune Checkpoint Inhibitors for Bladder Cancer
Atezolizumab: approved in May 2016, phase III testing ongoing
Durvalumab (FDA breakthrough status): phase III
Avelumab: phase III
Nivolumab: phase II and phase III
Pembrolizumab: phase III
However, the majority of pts do not benefit
Need to understand mechanisms of resistance
Combination approaches may be needed
Multiple combinations are possible
Slide credit: clinicaloptions.com

30. T-Cell Response: Accelerate or Brake?
Activating Signals
Inhibitory Signals
CD28
CTLA-4
OX40
T cell
GITR
PD-1
CD137
TIM-3
CD27
BTLA
HVEM
VISTA
LAG-3
T-Cell Stimulation
T-Cell Inhibition
Slide credit: clinicaloptions.com
Mellman I, et al. Nature. 2011;480:

31. Rationale for Combining Anti–PD-1/PD-L1 With Anti–CTLA-4 Approaches
Regulate immune responses through complementary mechanisms of action
Preventing T-cell exhaustion
Promoting T-cell activation
Activate quiescent T cells
However, higher toxicity due to peripheral T cell activation
Tumor Microenvironment
Activation (cytokines, lysis, proliferation, migration to tumor)
MHC, major histocompatibility complex; TCR, T-cell receptor.
MHC
TCR
MHC
TCR
Dendritic cell B7
CD28
PD-L1
Tumor cell
T cell
T cell B7
CTLA-4
Anti–PD-1
PD-L2
Anti–CTLA-4
Anti–PD-1
CTLA-4 Blockade
PD-1 Blockade
Slide credit: clinicaloptions.com
Hammers H et al. ASCO Abstract 4504.

32. Combinations May Only Be Needed in PD-L1–Negative Tumors
100
PFS: ITT Population 80
Addition of CTLA-4 inhibition may only lead to toxicity in patients with PD-L1– high tumors
No data yet in bladder cancer
Ipilimumab/nivolumab and durvalumab/ tremelimumab studies ongoing 60
PFS (%) 40 20 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21
100
Mos
PFS: PD-L1 Positive 80
Nivolumab
Nivolumab + ipilimumab
Ipilimumab 60
PFS (%) 40 20 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17
100
Mos
ITT, intent to treat.
PFS: PD-L1 Negative 80 60
PFS (%) 40 20 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21
Mos
Slide credit: clinicaloptions.com
Larkin J, et al. N Engl J Med. 2015;373:23-34.

33. Current Trials of Checkpoint Inhibitors in Bladder Cancer: Pembrolizumab
Trial Description
Phase
NCT#
Status
Pembrolizumab + acalabrutinib in platinum-resistant UBC II
NCT
Completed accrual
Pembrolizumab and vorinostat in advanced RCC or UC
NCT
Accruing
KEYNOTE-52: Pembrolizumab in cisplatin-ineligible advanced/metastatic urothelial cancer
NCT
Pembrolizumab in high-risk nonmuscle-invasive UBC with no response to BCG
NCT
Pembrolizumab and gemcitabine ± cisplatin prior to cystectomy in muscle-invasive UBC
NCT
Pembrolizumab maintenance vs placebo after first-line chemotherapy in metastatic UBC
NCT
KEYNOTE-045: Pembrolizumab vs paclitaxel, docetaxel, or vinflunine in platinum-refractory UC
III
NCT
UC, urothelial carcinoma; UBC, urothelial bladder cancer; BCG, Bacillus Calmette-Guerin vaccine.
Slide credit: clinicaloptions.com
ClinicalTrials.gov

34. Current Trials of Checkpoint Inhibitors in Bladder Cancer: Atezolizumab[1]
Trial Description
Phase
NCT#
Status
IMvigor210: Atezolizumab in advanced or metastatic UC* II
NCT
Completed accrual[2,3]
Preoperative atezolizumab in TCC
NCT
Accruing
IMvigor211: Atezolizumab vs chemotherapy in advanced/metastatic UC after failing platinum agents
III
NCT
Completed accrual
Atezolizumab vs observation as adjuvant therapy in PD-L1-selected high-risk MIBC
NCT
MIBC, muscle-invasive bladder cancer; TCC, transitional cell carcinoma; UC, urothelial carcinoma.
*Data from IMvigor210 will be presented Sunday, June 5 at 8:00 AM in Hall D2
1. ClinicalTrials.gov. 2. Balar AV, et al. ASCO Abstract LBA Rosenberg JE, et al. Lancet. 2016;387;
Slide credit: clinicaloptions.com

35. Current Trials of Checkpoint Inhibitors in Bladder Cancer: Other Agents[1]
Trial Description Ph
NCT#
Status
BISCAY: AZD4547 or durvalumab or durvalumab + either AZD4547, olaparib, or AZD1775 in MIBC after PD Ib
NCT
Not yet accruing
Nivolumab ± ipilimumab in UBC and other advanced solid tumors II
NCT
Completed accrual
Nivolumab in metastatic or unresectable UC after progression on a platinum agent
NCT
Ipilimumab, gemcitabine, cisplatin as neoadjuvant therapy for localized UC
NCT
Completed accrual[2]
Tremelimumab ± durvalumab in UBC, breast cancer, and pancreatic cancer
NCT
Accruing
DANUBE: Durvalumab ± tremelimumab vs chemotherapy in stage IV UBC
III
NCT
Avelumab vs BSC as maintenance after successful first-line therapy in advanced UC
NCT
CheckMate 274: Adjuvant nivolumab vs placebo in high-risk invasive UC
NCT
BSC, best supportive care; MIBC, muscle-invasive bladder cancer; PD, progressive disease; UBC, urothelial bladder cancer; UC, urothelial carcinoma of bladder, ureter, or renal pelvis
Slide credit: clinicaloptions.com
1. ClinicalTrials.gov. 2. Galsky MD, et al. ASCO GU Abstract 357.

36. Immune Checkpoint Blockade in Urothelial Carcinoma: Conclusions
Atezolizumab has promising clinical activity in heavily pretreated metastatic urothelial carcinoma[1]
Atezolizumab IHC assay measures PD-L1 expression on ICs
Higher PD-L1 expression is associated with higher response rates
Phase II ORRs: 26% and 15% in IC2/3 and all pts, respectively[2]
Early data with avelumab are encouraging
Pembrolizumab shows significant promise in the treatment of urothelial carcinoma[3]
Durable responses have been observed
Median survival was approximately 1 yr
ORR: 28%, including 10% CR
Nivolumab and durvalumab data to be presented at ASCO
IC, immune cell.
1. Rosenberg JE, et al. European Cancer Conference Abstract 21LBA. 2. Rosenberg JE, et al. Lancet. 2016;387:
3. Plimack ER, et al. ASCO Abstract 4502.
Slide credit: clinicaloptions.com

37. Go Online for More CCO Coverage of Bladder Cancer!
Downloadable slidesets on the clinical application of immunotherapy in bladder cancer On-demand Webcast from the live symposium CME-certified Expert Analysis of key ASCO 2016 abstracts on GU and other malignancies
clinicaloptions.com/oncology