1. IMvigor 210 (Cohort 2): Atezolizumab in Pretreated 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: Atezolizumab in Pretreated Metastatic UC: Background
Standard platinum-based chemotherapy for metastatic UC associated with nondurable responses and high rates of progression, grade 3/4 AEs, and death
Atezolizumab: first FDA-approved PD-L1 inhibitor (May 18, 2016)
For locally advanced UC or metastatic UC that progresses on or within 12 mos of platinum-containing chemotherapy
Current IMvigor210 study evaluated safety, efficacy of atezolizumab in platinum-pretreated metastatic UC pts with poor prognostic factors (cohort 2)
AE, adverse event; UC, urothelial carcinoma.
Slide credit: clinicaloptions.com
Dreicer R, et al. ASCO Abstract 4515.

3. cisplatin ineligible (n = 119)
IMvigor 210: Study Design
Single-arm phase II study with 2 cohorts[1]
Cohort 2 study
Primary endpoints: confirmed ORR by RECIST v1.1 (per central review), ORR per immune- modified RECIST (per investigator)
Secondary endpoints: DoR, PFS, OS, safety
Exploratory endpoints: biomarkers
Cohort 1[2]
Previously untreated,
cisplatin ineligible (n = 119)
Atezolizumab
1200 mg IV Q3W
until PD
Pts with inoperable advanced or metastatic UC, predominantly TCC histology, evaluable tumor tissue for
PD-L1 testing
(N = 429)
Cohort 2[3,4]
Prior platinum
treatment (n = 310)
Atezolizumab
1200 mg IV Q3W
until loss of benefit
DoR, duration of response; ORR, objective response rate; PD, progressive disease; RECIST, Response Evaluation Criteria in Solid Tumors; TCC, transitional cell carcinoma; UC, urothelial 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

4. IMvigor 210 (Cohort 2): Pt Characteristics
Characteristics representative of greater mUC population
Characteristic
Prior mUC
(n = 310)
Median age, yrs (range)
66 (32-91)
Male, % 78
PD-L1 status on immune cells: IC0/IC1/IC2/3,* %
33/35/32
Metastatic sites: visceral†/liver/lymph node only, %
78/31/14
Creatinine clearance mL/min, % 35
ECOG PS 1, % 62
Prior cystectomy or nephroureterectomy, % 66
Prior regimens in metastatic setting 1/2/≥ 3, %
40/21/21
ECOG, Eastern Cooperative Oncology Group; IC, immune cells; mUC, metastatic urothelial carcinoma; PS, performance status.
*PD-L1 IC assessed by VENTANA SP142 IHC assay: IC0 (< 1%), IC1 (≥ 1% to < 5%), IC2/3 (≥ 5%).
†Liver, lung, bone, nonlymph node, soft tissue metastases.
Dreicer R, et al. ASCO Abstract Rosenberg JE, et al. Lancet. 2016;387:
Slide credit: clinicaloptions.com

5. IMvigor 210 (Cohort 2): Response
Outcome, %
IC0
(n = 103)
IC1
(n = 107)
IC2/3
(n = 100)
All pts*
(n = 310)
ORR† (confirmed IRF) 9 11 28 16
CR (confirmed IRF) 2 4 15 7
Reduced tumor burden 30
(n = 84) 45
(n = 88) 61
(n = 87) 46
(n = 259)
*46 pts with missing/unevaluable responses included in ORR analysis.
†Per RECISTv1.1.
Responses seen in all PD-L1 IC subgroups
Strongest responses with higher PD-L1 IC status
Median time to first response: 2.1 mos (range: mos)
Additional and deeper responses observed with longer follow-up
At median 17.5 mos follow-up, 71% (35/49) of responses ongoing (including 86% of CRs)
mDoR not yet reached in any PD-L1 IC subgroup
IC, immune cell; IRF, independent review facility; mDoR, median duration of response; mUC, metastatic urothelial carcinoma; ORR, objective response rate; RECIST, Response Evaluation Criteria in Solid Tumors
Slide credit: clinicaloptions.com
Dreicer R, et al. ASCO Abstract 4515.

6. IMvigor 210 (Cohort 2): Change in Tumor Burden by PD-L1 Subgroup
100 *
Reduction in tumor burden associated with PD-L1 status
118/259 pts with tumor assessments (46%) had reductions in SLD of target lesions
IC2/3; 28% ORR†
-100
53/87 (61%)
100 **
IC1; 11% ORR†
Maximum SLD Reduction From Baseline, %
40/88 (45%)
-100
SLD, sum of the longest diameter; IRF, independent review facility.
100 **
IC0; 9% ORR†
RECIST v1.1 Response
PD SD
PR CR
25/84 (30%)
-100
*> 100%. †Per IRF RECIST v1.1. Data cutoff: March 14, 2016.
Slide credit: clinicaloptions.com
Dreicer R, et al. ASCO Abstract 4515.

7. IMvigor 210 (Cohort 2): 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
Dreicer R, et al. ASCO Abstract 4515.
Rosenberg JE, et al. Lancet. 2016;387:
Slide credit: clinicaloptions.com

8. IMvigor 210 (Cohort 2): Safety
AE, % (n = 310)
Any
Cause
Treatment
Related
Any AE 97 70
Serious AE 46 12
Grade 3/4 57 16
Grade 5 1
31% with AE (any cause) leading to dose interruption; 3% leading to treatment withdrawal
Most treatment-related AEs were grade 1/2 (most common: fatigue, nausea, decreased appetite, pruritis)
No decline in renal function in pts with prior renal impairment
6% had grade 3/4 immunologic AE requiring steroids
Grade 5 AEs: cerebral hemorrhage, pulmonary sepsis, and intestinal obstruction
AE, adverse event.
Slide credit: clinicaloptions.com
Dreicer R, et al. ASCO Abstract 4515.

9. IMvigor 210 (Cohort 2): Conclusions
Atezolizumab produced rapid and durable responses in mUC pts with poor prognostic factors who progressed on previous platinum-containing treatment[1]
Responses seen in all PD-L1 IC subgroups, enriched in those with higher PD-L1 IC status
Additional and deeper responses with no added safety concerns seen with longer follow-up
Early survival data favorable in all PD-L1 IC subgroups
Data led to accelerated approval of atezolizumab for advanced or metastatic UC after PD during or following platinum-based therapy
Investigators suggest atezolizumab has potential as new standard of care in mUC, pending further investigation
Randomized phase III trial vs chemotherapy now ongoing[2]
IC, immune cell; mUC, metastatic urothelial carcinoma; PD, progressive disease.
1. Dreicer R, et al. ASCO Abstract 4515.
2. ClinicalTrials.gov. NCT
Slide credit: clinicaloptions.com

10. Go Online for More CCO Coverage of ASCO 2016!
Short slideset summaries of all the key data
Additional CME-certified analyses with expert faculty commentary on all the key studies in:
Breast, genitourinary, and lung cancers
Hematologic malignancies
Immunotherapy
clinicaloptions.com/oncology