1. IMvigor 210 (Cohort 1): First-line Atezolizumab in Cisplatin-Ineligible Metastatic Urothelial Carcinoma
CCO Independent Conference Coverage* of the 2016 ASCO Annual Meeting, June 3-7, 2016
*CCO is an independent medical education company that provides state-of-the-art medical information to healthcare professionals through conference coverage and other educational programs.
This activity is supported by educational grants from Amgen, Ariad, Bayer Healthcare Pharmaceuticals, Celgene Corporation, Genentech, Incyte, Merck, and Taiho Pharmaceuticals.

2. IMvigor 210 (Cohort 1): Background
Cisplatin the is first-line standard of care for metastatic urothelial carcinoma
Most pts are cisplatin ineligible due to poor performance status, impaired renal function, or comorbidities[1]
Non-cisplatin–based regimens associated with short response duration, lack of survival benefit, high discontinuation rate[2]
Atezolizumab: engineered mAb targeting PD-L1 immune checkpoint
Active, well tolerated in treatment-experienced mUC[3]
Currently FDA approved only in cisplatin-treated pts
Cohort 1 of the IMvigor 210 study evaluated safety, efficacy of atezolizumab as first-line therapy in untreated, cisplatin-ineligible mUC pts[4]
mAb, monoclonal antibody; mUC, metastatic urothelial carcinoma.
1. Galasky MD. ECC Abstract De Santis M, et al. J Clin Oncol. 2012;30: Rosenberg JE, et al. Lancet. 2016;387: Balar AV, et al. ASCO Abstract LBA4500.
Slide credit: clinicaloptions.com

3. cisplatin ineligible*
IMvigor 210: Study Design
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]
prior platinum
treatment
Atezolizumab
1200 mg IV Q3W
until loss of benefit
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 of the following: ECOG PS 2; grade ≥ 2 hearing loss or peripheral
neuropathy; renal impairment (eGFRCG: > 30, < 60 mL/min).
Cohort 1 study
Primary endpoint: confirmed ORR by RECIST v1.1 (per central, independent review)
Secondary endpoints: DoR, PFS, OS, safety
1. ClinicalTrials.gov. NCT Balar AV, et al. ASCO Abstract LBA Dreicer R, et al. ASCO Abstract 4515.
Slide credit: clinicaloptions.com

4. IMvigor 210 (Cohort 1): Pt Characteristics
Characteristics consistent across PD-L1 IC subgroups
Characteristic
Cisplatin-Ineligible mUC
(N = 119)
Median age, yrs (range)
80 yrs or older, %
73 (51-92) 21
Male, % 81
PD-L1 status on immune cells: IC0/IC1/IC2/3, %
33/40/27
Metastatic disease, %
Visceral sites 92 66
Cisplatin ineligibility criteria, %
Renal impairment (eGFRCG: > 30, < 60 mL/min)
Hearing loss (25 dB)
Peripheral neuropathy (grade ≥ 2)
ECOG PS 2 70 14 6 20
ECOG, Eastern Cooperative Oncology Group; eGFRCG, estimated Glomerular Filtration Rate Cockcroft-Gault; IC, immune cell; mUC, metastatic urothelial carcinoma; PS, performance status.
Slide credit: clinicaloptions.com
Balar AV, et al. ASCO Abstract LBA4500.

5. IMvigor 210 (Cohort 1): Response
Outcome
IC0
(n = 39)
IC1
(n = 48)
IC2/3
(n = 32)
All Pts
(N = 119)
ORR,* % CR PR 21 8 13 23 6 17 28 22 24 7
Median time to response,† mos
2.0
( )
2.4
( )
2.1
( ) --
Reduced tumor burden, % 63
(n = 30) 51 65
(n = 26) 59
(n = 95)
*19 pts with missing/unevaluable responses included in ORR analysis. †Responders only.
DoR, duration of response; IC, immune cell; ORR, objective response rate.
Median DoR not reached in any PD-L1 IC subgroup
Responses seen in all analyzed subgroups including poor baseline prognostic factors, pts 80 yrs of age or older
ORR similar for all cisplatin-ineligible criteria subgroups
Slide credit: clinicaloptions.com
Balar AV, et al. ASCO Abstract LBA4500.

6. IMvigor 210 (Cohort 1): Change in Tumor Burden
59% of all evaluable pts had decreased target lesions
Median follow- up: 14.4 mos (range, )
100
IC2/3; 28% ORR
17/26 (65%)
-100
100
IC1; 23% ORR
Maximum SLD Reduction From Baseline, %
20/39 (51%)
RECIST v1.1 Response
-100
IC, immune cell; RECIST, Response Evaluation Criteria in Solid Tumors; SLD, sum of the longest diameter.
PD SD PR CR
100
IC0; 21% ORR
-100
19/30 (63%)
Balar AV, et al. ASCO Abstract LBA4500. Reproduced with permission.
Slide credit: clinicaloptions.com

7. IMvigor 210 (Cohort 1): OS
OS by PD-L1 Status[1]
100
Subgroup
mOS (95% CI)
All (N = 119) IC0/1 (n = 87) IC2/3 (n = 32)
14.8 mo (10.1-NE) 15.3 mo (9.8-NE)
12.3 mo (6.0-NE) 80 60
Overall Survival, %
12-mo OS rate:
57% (95% CI: 48-66) 40 20 2 4 6 8 10 12 14 16 18 20
Time, mos
IC, immune cell; NE, not estimable; mOS, median overall survival; IC, immune cell.
Favorable preliminary survival outcomes vs historic data from non-cisplatin regimens[2,3]
Survival similar in all PD-L1 IC subgroups
98 pts discontinued
26 pts went on to receive subsequent therapy postprotocol
1. Balar AV, et al. ASCO Abstract LBA4500. Reproduced with permission. 2. De Santis M, et al. J Clin Oncol. 2012;30: Galsky MD, et al. ECC Abstract 2624.
Slide credit: clinicaloptions.com

8. IMvigor 210 (Cohort 1): Safety
AE, % (N = 119)
Any Cause
Treatment Related
Any AE 96 66
Serious AE 36 8
Grade 3/4 45 15
Grade 5 3 1
35% had AE leading to dose interruption; 6% leading to treatment withdrawal
Most treatment-related AEs grade 1/2; only a single treatment- related grade 5 AE (sepsis)
No decline in renal function in pts with prior renal impairment
6% had grade 3/4 immune-related AE requiring steroids
AE, adverse event.
Slide credit: clinicaloptions.com
Balar AV, et al. ASCO Abstract LBA4500.

9. IMvigor 210 (Cohort 1): Treatment- and Immune-Related AEs
Treatment-Related AEs in ≥ 5% of Pts, %
(N = 119)
All Grades
Grade 3/4
Fatigue 30 3
Diarrhea 11 1
Pruritus
Anorexia 9
Hypothyroidism 6
Anemia 5
Chills
Nausea
Pyrexia
Rash
Vomiting
Immune-Related AEs,* %
(N = 119)
All Grades
Grade 3/4
Rash 3 1
Pruritus
ALT ↑ 2
Serum bilirubin ↑
Rhabdomyolysis
AST increased
Autoimmune colitis
Colitis
Hyperglycemia
Liver disorder
AE, adverse event; ALT, alanine aminotransferase; AST, aspartate aminotransferase.
*Requiring systemic corticosteroids.
Slide credit: clinicaloptions.com
Balar AV, et al. ASCO Abstract LBA4500.

10. IMvigor 210 (Cohort 1): Conclusions
Rapid and durable responses to atezolizumab in previously untreated cisplatin-ineligible mUC
Responses seen in all PD-L1 IC subgroups
75% (21/28) responses ongoing after data cutoff
Early survival data favorable in all PD-L1 IC subgroups
Well-tolerated safety profile with few treatment-related grade ≥ 3 AEs
Investigators suggest atezolizumab has potential as new standard-of-care therapy in cisplatin-ineligible pts, pending further investigation
AE, adverse event; IC, immune cell; mUC, metastatic urothelial carcinoma.
Slide credit: clinicaloptions.com
Balar AV, et al. ASCO Abstract LBA4500.

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