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1. New Thinking, New Strategies in
Advanced Urothelial Carcinoma
Arjun Balar, MD
Associate Professor of Medicine
Director, Genitourinary Medical Oncology Program
Perlmutter Cancer Center

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3. Disclosures
Dr. Balar discloses the following commercial relationships:
Consultant/advisor: AstraZeneca/Medimmune, Genentech, Incyte, Janssen, Merck,
Nektar, Pfizer, Seattle Genetics
Research support: AstraZeneca/Medimmune, Genentech, Immunomedics, Merck,
Nektar, Seattle Genetics
Speaker: AstraZeneca/Medimmune, Genentech, Merck
Steering committee: Merck, Nektar

4. Learning Objectives
Evaluate patient- and tumor-related factors that can inform
personalized care plans for patients with urothelial carcinoma
Differentiate the mechanism of action of novel therapies for locally
advanced/metastatic urothelial carcinoma
Assess emerging clinical evidence on novel treatment approaches for
patients with locally advanced/metastatic urothelial carcinoma,
including those ineligible for cisplatin-based chemotherapy

5. Urothelial Cancer Management in the US: An Overview
CIS = carcinoma in situ; NMIBC = non-muscle invasive bladder cancer; TURBT = transurethral resection of bladder tumor;
BCG = Bacillus Calmette-Guerin; gem = gemcitabine; cis = cisplatin; MVAC = methotrexate/vinblastine/doxorubicin/cisplatin;
SOC = standard of care; carbo = carboplatin; ORR = overall response rate; mOS = median overall survival; mo = months.
NCCN, 2019; Hsu et al, 2017.
Fat
Muscle
CIS
Ta
T1
T2
T3
T4
Connective tissue
Bladder lining
Estimated 2019 US Incidence:
~80,470 cases
~17,670 deaths

6. Metastatic Urothelial Cancer: Overview
In 2019 in the US, the estimated incidence was 80,470, with 17,670 disease-related deaths
Notable facts:
Men:women ratio of 3:1
Median age 73 years at diagnosis
Tobacco use is the most common culprit
Metastatic urothelial cancer is a chemotherapy-sensitive disease
Eg, cisplatin, carboplatin, methotrexate, doxorubicin, vinblastine, ifosfamide, gemcitabine, paclitaxel, and
docetaxel
Cisplatin and methotrexate have the highest response rates as single agents (20-30%)
Basis for combination regimens (MVAC, CISCA, etc)
Cisplatin-based therapy improves survival and a small proportion of patients (~10%) are cured
Substantial toxicity is associated with cisplatin
After first-line treatment failure, outcome is very poor (median survival 5-7 months)
CISCA = cisplatin/doxorubicin/cyclophosphamide.
NCCN, 2019.

7. High mutational complexity rates linked to tobacco/environmental carcinogen exposure
Potential for many neoantigens to be seen as foreign by host immune system
Somatic Mutational Burden Is High in UBC
UBC = urothelial bladder cancer; Mb = megabase.
Lawrence et al, 2013; Bellmunt, Powles, et al, 2017.

8. The Cancer-Immunity Cycle
APC = antigen presenting cells; CTLs = cytotoxic T-lymphocytes.
Chen & Mellman, 2013.

9. PD-1/PD-L1 Antibodies in Urothelial Cancer
PD-1 = programmed cell death protein 1; PD-L1 = programmed death-ligand 1.
Plimack et al, 2017.
Pembrolizumab phase 1b study in metastatic UBC (KEYNOTE-012)
Median time to response: 2 months (range 2-13 months)
Median duration of response: 10 months (range 4-22+ months)

10. KEYNOTE-045 Study Design (NCT02256436)
PD = progressive disease; chemo = chemotherapy; ECOG = Eastern Cooperative Oncology Group;
PS = performance status; R = randomized; IV = intravenous; Q3W = every 3 weeks; OS = overall survival;
PFS = progression-free survival; CPS = combined positive score; DOR = duration of response.
Bellmunt, Wit, et al, 2017.
Key End Points
Primary: OS and PFS in total and PD-L1 CPS ≥10% populations
Secondary: ORR and DOR in total and PD-L1 CPS ≥10% populations;
safety in total population
Key Eligibility Criteria
• Urothelial carcinoma of the renal pelvis,
ureter, bladder, or urethra
• Transitional cell predominant
• PD after 1-2 lines of platinum-based
chemo or recurrence within 12 mo of
perioperative platinum-based therapy
• ECOG PS 0-2
• Provision of tumor sample for biomarker
assessment
Pembrolizumab
200 mg IV Q3W
for 2 years
Paclitaxel 175 mg/m2 Q3W
or
Docetaxel 75 mg/m2 Q3W
or
Vinflunine 320 mg/m2 Q3W
R (1:1)
N=542
n=270
n=272
Stratification Factors
• ECOG PS (0/1 vs 2)
• Hemoglobin level (<10 vs ≥10 g/dL)
• Liver metastases (yes vs no)
• Time from last chemotherapy dose
(<3 vs ≥3 mo)

11. Overall Survival: Total
aBased on Cox regression model with treatment as a covariate stratified by ECOG performance status (0/1 vs 2), liver metastases (yes vs no),
hemoglobin (<10 vs ≥10 g/dL), and time from completion of chemotherapy (<3 vs ≥3 months).
bOne-sided P value based on stratified log-rank test.
n = number; HR = hazard ratio; CI = confidence interval; pembro = pembrolizumab.
Bellmunt, Wit, et al, 2017.
Data cutoff date: October 26, 2017

12. Checkpoint Inhibitors Approved for Use in Urothelial Carcinoma
aPembrolizumab arm.
NCCN, 2019; Rosenberg et al, 2016; Patel et al, 2018.
Efficacy
Setting Antibody (Study) N ORR Median OS
Platinum-
pretreated
Atezolizumab
(IMvigor210, Cohort 2)
310 15% 7.9 months
Nivolumab
(CheckMate 275)
265 20% 8.74 months
Durvalumab
(Study 1108)
191 18% 18.2 months
Avelumab
(JAVELIN Solid Tumor)
249 17% 7.7 months
Pembrolizumab
(KEYNOTE-045 [Phase 3])
270a 21% 10.3 months

13. Immune-Related Adverse Events from CPIs
Hepatic
Autoimmune hepatitis
ALT/AST increases
Renal
Nephritis
Renal failure
Skin
Maculopapular rash
Pruritus
Gastrointestinal
Colitis/diarrhea
ALT = alanine transaminase; AST = aspartate transaminase; CPIs = checkpoint inhibitors.
Hsu et al, 2017.
Endocrine
Hypophysitis
Thyroiditis
Type 1 diabetes
Respiratory
Pneumonitis
Neuromuscular
Peripheral sensory neuropathy

14. Patient Case Study 1: Second-Line mUC
mUC = metastatic urothelial carcinoma; MIBC = muscle invasive bladder cancer; LN = lymph node;
mets = metastasis; BC = bladder cancer.
High-
grade
MIBC and
LN mets
Gemcitabine/cisplatin
December
2017
January
2018
Presented
with
hematuria
June
2017
!
September
2017
August
2017
Progression
High-grade BC with progression
to liver metastases
62-year-old man
6 cycles
?????

15. What is the most appropriate treatment option?
A. Gemcitabine and carboplatin
B. Paclitaxel
C. Axitinib plus pembrolizumab
D. Anti–PD-1 or anti–PD-L1 antibody
E. Docetaxel
F. Not sure/something else

16. Patient Case Study 1: Second-Line mUC (cont.)
High-
grade
MIBC and
LN mets
January
2018
Gemcitabine/cisplatin
December
2017
January
2018
Presented
with
hematuria
June
2017
!
September
2017
August
2017
Progression
High-grade BC with progression
to liver metastases
Anti–PD-1/L1 antibody
62-year-old man
6 cycles

17. January 2018 Progression in Liver
MRI = magnetic resonance imaging; DWI = diffusion-weighted imaging.
Image courtesy of Dr. Balar.
Multiple new liver metastases
(MRI with DWI)

18. March 2018 After 3 Cycles
Image courtesy of Dr Balar.
Liver metastases responding
(MRI with DWI)

19. Cisplatin-Ineligible Patients With Muscle-Invasive and
Metastatic Urothelial Cancer
Sonpavde et al, 2014; De Santis et al, 2012.
Median OS: 9 months
Cisplatin improves survival
(including cures); however, 50% to
70% of patients are ineligible due to
comorbidities
PS and renal dysfunction
Neuropathy/hearing loss
Heart failure
Cisplatin-ineligible
Outcomes are very poor with alternative
chemotherapy
20% to 40% or more are never treated

20. Phase 2 Trials in 1L Cisplatin-Ineligible mUC
1L = first-line; CrCl = creatine clearance; ITT = intention to treat.
Balar et al, 2017a; Balar et al, 2017b.
Primary end point: ORR
Secondary end points: PFS, DOR, OS, and safety
Atezolizumab
• 1L, locally advanced/mUC
• No prior treatment for mUC
• Cisplatin-ineligible based on
– CrCl <60 and >30mL/min
– Grade ≥2 hearing loss
– Grade ≥2 peripheral
neuropathy
– ECOG PS 2
• ECOG PS 0-2
n=119
Co-primary end points: ORR in ITT population; ORR in PD-L1+ patients
Secondary end points: DOR, PFS, OS, and ORR in ITT and PD-L1+
patients; safety and tolerability
Pembrolizumab
IMvigor210 Cohort 1 KEYNOTE-052
• 1L, locally advanced/mUC
• No prior treatment for mUC
• Cisplatin-ineligible based on
– CrCl <60 mL/min
– Grade ≥2 hearing loss
– Grade ≥2 peripheral
neuropathy
– ECOG PS 2
• ECOG PS 0-2
N=370

21. Cisplatin-Ineligible Patients and First-Line Immunotherapy
Balar et al, 2018; Balar et al, 2017; Vuky et al, 2018; Powles et al, 2017; Galsky et al, 2018.
Enthusiasm for activity in second-line
inspired testing in first-line cisplatin-
ineligible
Two single-arm studies (IMVigor 210
C1 and KEYNOTE-052)
Accelerated approval based on response
(including durability) and safety
Immediately expanded the treatable
population with advanced urothelial
cancer
Chemo-ineligible patients now have an
option
Safety alerts (KEYNOTE-361 and
IMVigor130) have better defined
appropriate patients for therapy

22. Cisplatin-Ineligible Patients and First-Line Immunotherapy (cont.)
FDA, 2018a; Powles et al, 2017; Galsky et al, 2018.
Atezolizumab (April 2017) and pembrolizumab (May 2017) FDA approved for first-line treatment of
cisplatin-ineligible patients
On the basis of single-arm phase 2 trials (IMVigor 210 Cohort 1 and KEYNOTE-052)
May 2018 FDA issued a safety alert on decreased survival with pembro or atezo as monotherapy
in 2 clinical trials of patients with mUC who have not received prior therapy and who have low PD-
L1 expression:
Patients in these studies were platinum-eligible
Enrollment continues for other arms of these trials

23. Pembro and Atezo Labels Updated August 2018
IC = immune cell.
FDA, 2018b.
Requires use of an FDA-approved companion diagnostic test to determine PD-L1 levels in
tumor tissue
Pembrolizumab: indicated for the treatment of patients with locally advanced/metastatic
urothelial carcinoma who are ineligible for cisplatin-containing chemotherapy and whose
tumors express PD-L1 (CPS ≥10) as determined by an FDA-approved test, or in patients who
are ineligible for any platinum-containing chemotherapy regardless of PD-L1 status
Atezolizumab: indicated for the treatment of patients with locally advanced or metastatic
urothelial carcinoma who are ineligible for cisplatin-containing chemotherapy and whose
tumors express PD-L1 (PD-L1–stained tumor-infiltrating ICs covering ≥5% of the tumor area)
as determined by an FDA-approved test, or who are ineligible for any platinum-containing
therapy regardless of level of tumor PD-L1 expression
For Advanced Cisplatin-Ineligible Bladder Cancer

24. IMvigor130
Plt = platinum.
Grande et al, 2019.
Phase 3 study of atezolizumab ± platinum-based chemo in patients with
previously untreated mUC

25. Interim OS: PD-L1 Status (Arm B vs Arm C)
IC = immune cells; NE = not estimable.
Grande et al, 2019.
Arm B
Atezo
(n = 272)
Arm C
Placebo + plt/gem
(n = 274)
OS events, n (%) 158 (58) 156 (57)
Unstratified HR (95% CI) 1.07 (0.86, 1.33)
PD-L1 IC0/1
OS(%)
Months Months
Atezo 272 210 175 152 124 85 48 28 11 NE NE NE
274 246 212 173 116 73 41 21 10 2 NE NE
Arm B
Atezo
(n = 88)
Arm C
Placebo + plt/gem
(n = 85)
OS events, n (%) 33 (38) 42 (49)
Stratified HR (95% CI) 0.68 (0.43, 1.08)
PD-L1 IC2/3
88 75 70 64 49 35 24 14 5 NE NE NE
85 76 62 51 42 30 21 14 5 1 NE NE
Data cutoff 31 May 2019; median survival follow-up 11.8 months (all patients).
12.9 mo
(11.3, 15.0)
13.5 mo
(11.1, 16.4)
0 3 6 9 12 15 18 21 24 27 30 33
17.8 mo
(10.0, NE)
NE
(17.7, NE)
100
90
80
70
60
50
40
30
20
10
0
0 3 6 9 12 15 18 21 24 27 30 33

26. Beyond Immune Checkpoint Blockade: New Agents
Antibody-drug conjugates
Enfortumab vedotin
FDA approved December 2019 for locally advanced/metastatic urothelial cancer who
have previously received a PD-1/PD-L1 inhibitor, and a platinum-containing
chemotherapy
Molecularly targeted agents
FGFR3 inhibitors (erdafitinib)

27. Enfortumab Vedotin
Antibody-Drug Conjugate That Targets Nectin-4
EV = enfortumab vedotin.
Rosenberg et al, 2018; Seattle Genetics, 2019; Petrylak et al, 2017.
Enfortumab vedotin consists of a fully
humanized monoclonal antibody
targeting Nectin-4 and the
microtubule-disrupting agent
monomethyl auristatin E, conjugated
by a protease-cleavable linker
Nectin-4, a transmembrane cell adhesion
molecule, is highly expressed in cancer cells,
particularly in urothelial cancers
Nectin-4 was found to be highly expressed in
93% of mUC patient samples
Proposed mechanism of action of EV

28. EV-201: Single-Arm, Pivotal Phase 2Trial
a3 patients did not receive enfortumab vedotin treatment, 1 each due to clinical deterioration, patient decision,
and low hemoglobin after enrollment.
RECIST = Response Evaluation Criteria in Solid Tumors; BICR = blinded independent central review.
Rosenberg et al, 2019.
Enfortumab vedotin
1.25 mg/kg IV on days 1,
8, and15
of each 28-daycycle
Primary end point:
ORR per RECIST version 1.1 as
determined by BICR
Select secondary end points:
DOR
PFS
OS
Safety
Cohort 1
Prior PD-L1 inhibitor and
platinum-based therapy
Enrollment completed July
2018
n=128a
Cohort 2
Prior PD-L1 inhibitor,
platinum naive,
cisplatin ineligible
Enrollment ongoing
Screeningand enrollment at 51
sites in the US and Japan
Previously treated locally
advanced or metastatic
urothelial cancer

29. EV-201: Cohort 1 ORR With Enfortumab Vedotin
aComputed using the Clopper-Pearson method.
bIncludes 10 patients who discontinued study prior to post-baseline response assessment, 1 patient who had
uninterpretable post-baseline assessment, and 1 patient whose post-baseline assessment did not meet the minimum
interval requirement for stable disease.
Rosenberg et al, 2019.
ORR per RECIST 1.1 Assessed by BICR Patients (n=125) n (%)
Confirmed objective response rate 55 (44)
95% confidence intervala (35.1, 53.2)
Best overall response per RECIST 1.1, n (%)
Complete response 15 (12)
Partial response 40 (32)
Stable disease 35 (28)
Progressive disease 23 (18)
Not evaluableb 12 (10)

30. EV-201: Cohort 1 Change in Tumor Measurements per BICR
Rosenberg et al, 2019.
10 patients had no post-baseline assessment
4 patients had no target lesions identified at
baseline
1 patient had an uninterpretable post-baseline
assessment
n=110 patients with target lesions and adequate post-baseline assessment
84%

31. EV-201: Cohort 1 Treatment-Related Adverse Events
AEs = adverse events.
Rosenberg et al, 2019.
Treatment-related AEs led to few
discontinuations (12%)
Peripheral sensory neuropathy was
the most common (6%)
1 treatment-related death reported
by the investigator
Interstitial lung disease
Confounded by high-dose
corticosteroid use and suspected
pneumocystis jiroveci pneumonia
Treatment-RelatedAEs in
≥20% of Patients (Any Grade)
or ≥5% (Grade 3)
Patients (n=125)
n (%)
Any
Grade
Grade
≥3
Fatigue 62 (50) 7 (6)
Alopecia 61 (49) ‒
Decreased appetite 55 (44) 1 (1)
Dysgeusia 50 (40) ‒
Peripheral sensory neuropathy 50 (40) 2 (2)
Nausea 49 (39) 3 (2)
Diarrhea 40 (32) 3 (2)
Dry skin 28 (22) 0
Weight loss 28 (22) 1 (1)
Maculopapular rash 27 (22) 5 (4)
Anemia 22 (18) 9 (7)
Neutropenia 13 (10) 10 (8)

32. The Future of EV in mUC
Hoimes et al, 2019; Rosenberg et al, 2019; Clinicaltrials.gov, 2019a.
Ongoing studies
EV-103: phase 1 study of EV combined with pembrolizumab in mUC
(NCT03288545) — presented at ESMO 2019
EV-201: pivotal phase 2 study of EV in patients with locally advanced UC or
mUC who had previously received CPIs (NCT03219333)
Cohort 1: Patients must also have had prior treatment with platinum-containing
chemotherapy
Cohort 2: Patients must be platinum-naive and ineligible for cisplatin treatment
Enrollment ongoing
EV-301: phase 3 study of EV versus chemotherapy in mUC after prior
platinum-containing chemotherapy and CPI (NCT03474107)

33. EV-103: Enfortumab Vedotin/Pembrolizumab
CR = complete response; PR = partial response.
Hoimes et al, 2019.
Locally Advanced or Metastatic Urothelial Carcinoma

34. Percent Change From Baseline in Sum of Diameters of Target Lesions
Hoimes et al, 2019.
91% of responses observed
at first assessment
(Week 9 ± 1 week)
Median time to response: 2.0
months
(range: 1.4-4.2 months)
DOR range: 1.0-10.5 months
and ongoing
22 of 32 responders remain
on treatment

35. FGFR3 Alterations in High-Grade UC
TCGA = The Cancer Genome Atlas.
Balar & Milowsky, 2015.

36. Erdafitinib Is a Potent FGFR Inhibitor
Erdafitinib is an oral pan-FGFR (1-4) inhibitor
Single-digit nanomolar range
Erdafitinib is taken up by lysosomes, resulting in sustained intracellular release, which
may contribute to its long-lasting activity
Erdafitinib has demonstrated promising activity in patients with
metastatic or unresectable UC and other histologies (eg,
cholangiocarcinoma) with FGFR
Abbreviation: IC50, drug concentration at which 50% of target enzyme
activity is inhibited
IC50 in the alterations
Perera et al, 2017; Tabernero et al, 2015; Soria et al, 2016; Loriot et al, 2018; Siefker-Radtke et al, 2018.

37. Phase 2 BLC2001 Study of Erdafitinib in FGFR-
Altered mUC
QD = daily; PCR = polymerase chain reaction.
Loriot et al, 2019.
Study evaluated multiple dose/schedules
8 mg QD (N=99)
Centrally selected for FGFR fusions or mutations (PCR-based assay)
FGFR3 activating mutations
R248C, S249C, G370C, Y373C
FGFR fusions
FGFR3-TACC3
FGFR3-BAIAP2L1
FGFR2-BICC1
FGFR2-CASP7

38. Phase 2 Erdafitinib in FGFR–Altered mUC
aPer investigator assessment and confirmed with second scan ≥6 weeks following initial observation of response.
Loriot et al, 2019.
21.2% of patients remain on study treatment after 11 months of follow-up
Patients (N=99) Responsea: n (%) [95% CI]
ORR 40 (40.4%) [30.7–50.1]
Complete response 3 (3%)
Partial response 37 (37.4%)
Stable disease 39 (39.4%)
Progressive disease 18 (18.2%)
Median time to response 1.4 months
Median duration of response 5.6 months [4.2–7.2]
ORR among patient subgroups, n (%)
Chemo-naive vs progressed/relapsed
after chemo
5/12 (41.7%) vs 35/87
With vs without visceral metastases 30/78 (38.5%) vs 10/21

39. Erdafitinib: TRAEs of Clinical Importance/Special Interest
aMost common non-CSR ocular events included dry eye (19%), blurry vision (16%), increased lacrimation (11%),
and conjunctivitis (9%).
TRAEs = treatment-related adverse events; MAPK = mitogen activated protein kinase.
Renouf et al, 2012; Stjepanovic et al, 2016.
39
Patients with AEs, n (%)
Any grade Grade ≥3
Hyperphosphatemia 72 (73) 2 (2)
Skin events 48 (49) 6 (6)
Dry skin 32 (32) 0 (0)
Hand-foot syndrome 22 (22) 5 (5)
Nail events 51 (52) 14 (14)
Onycholysis 16 (16) 2 (2)
Paronychia 14 (14) 3 (3)
Nail Dystrophy 16 (16) 6 (6)
Central serous retinopathy
(CSR)
21 (21) 3 (3)
Non-CSR ocular eventsa 51 (52) 5 (5)
Majority of events were grade 1/2
Few patients (n=7) discontinued
because of AEs of special interest
All AEs of special interest were
managed with supportive
therapies, dose interruption,
and/or modification
CSR is a known class effect of the
MAPK pathway
Patients were routinely monitored
CSR rarely led to discontinuation
(n=3), and no patient had retinal
vein or artery occlusion

40. Erdafitinib: Role in Advanced mUC
RGQ = Rotor-Gene Q; RT = reverse transcription.
NCCN, 2019; Clinicaltrials.gov, 2018b; Clinicaltrials.gov, 2019c.
Breakthrough Therapy Designation status (March 2018)
FDA approved in April 2019
FGFR3 mutations or FGFR2 or FGFR3 fusions (Therascreen® FGFR RGQ RT-PCR
Kit)
Erdafitinib 8 mg daily starting dose
Uptitration to 9 mg daily (serum phosphate remained <5.5 mg/dL)
Other ongoing mUC studies
Phase 3 THOR trial of erdafitinib versus chemotherapy or pembrolizumab
(NCT0333905054)
Phase 1b/2 NORSE trial of erdafitinib plus cetrelimab (anti-PD-1 antibody)
(NCT03473743)

41. Key Takeaways
IO = immuno-oncology; ADCs = antibody-drug conjugates.
PD-1 pathway inhibitors have revolutionized bladder cancer
management and how we think about the disease
Expanded the treatable population with bladder cancer
Novel combinatorial strategies (chemo-based, IO-based) could lead to
new standards of care and may be broadly applicable
Cytotoxics still have an important role, and ADCs have improved
therapeutic index
Enfortumab vedotin (and sacituzumab govitecan) are poised to be excellent
options post-IO
First-line EV with anti PD-1 suggests immune synergy and could challenge first-
line platinum

42. Key Takeaways (cont.)
FGF(R) pathway is targetable, and scope of activity may not be
limited to receptor alterations
The most significant impact is yet to come
Early-stage disease (MIBC and NMIBC)

43. Thank you for joining us!
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44. References
Balar AV, Galsky MD, Loriot Y, et al (2017a). Atezolizumab (atezo) as first-line (1L) therapy in cisplatin-ineligible locally advanced/metastatic urothelial
carcinoma (mUC): primary analysis of IMvigor cohort 1. J Clin Oncol, 34(18_suppl). DOI:10.1200/JCO.2016.34.18_suppl.LBA4500
Balar AV, Castellano D, O’Donnel PH, et al (2017b). First-line pembrolizumab in cisplatin-ineligible patients with locally advanced and unresectable or
metastatic urothelial cancer (KEYNOTE-052): a multicenter, single-arm, phase 2 study. Lancet Oncol, 18(11):1483-1492. DOI:10.1016/S147-
2045(17)30616-2
Balar AV, Dreicer R, Loriot Y, et al (2018). Atezolizumab (atezo) in first-line cisplatin-ineligible or platinum-treated locally advanced or metastatic urothelial
cancer (mUC): long-term efficacy from phase 2 study IMvigor210. J Clin Oncol (ASCO Annual Meeting Abstracts), 36(suppl_15). Abstract 4523.
DOI:10.1200/JCO.2018.36.15_suppl.4523
Balar AV & Milowsky MI (2015). Cytotoxic and DNA-targeted therapy in urothelial cancer: have we squeezed the lemon enough? Cancer, 121(2):179-187.
DOI:10.1002/cncr.28754
Bellmunt J, Powles T & Vogelzang NJ (2017). A review on the evolution of PD-1/PD-L1 immunotherapy for bladder cancer: the future is now. Cancer Treat
Rev, 54:58-67. DOI:10.1016/j.ctrv.2017.01.007
Bellmunt J, Wit RD, Vaughn DJ, et al (2017). Pembrolizumab as second-line therapy for advanced urothelial carcinoma. N Engl J Med, 376:1015-1026.
DOI:10.1056/NEJMoa1613683
Chen DS & Mellman I (2013). Oncology meets immunology: the cancer-immunity cycle. Immunity, 39:1-10. DOI:10.1016/j.immune.2013.07.012
Clinicaltrials.gov (2019a). A study to evaluate enfortumab vedotin versus (vs) chemotherapy in subjects with previously treated locally advanced or metastatic
urothelial cancer (EV-301). NLM identifier: NCT03474107.
Clinicaltrials.gov (2019b). A study of erdafitinib compared with vinflunine or docetaxel or pembrolizumab in participants with advanced urothelial cancer and
selected fibroblast growth factor receptor (FGFR) gene aberrations. NLM identifier: NCT03390504.
Clinicaltrials.gov (2019c). A study to evaluate safety, efficacy, pharmacokinetics, and pharmacodynamics of erdafitinib plus JNJ-63723283 (cetrelimab), an anti-
PD-1 monoclonal antibody, in participants with metastatic or locally advanced urothelial cancer with selected FGFR gene alterations. NLM identifier:
NCT03473743.

45. References (cont.)
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