1. KEYNOTE-087: Pembrolizumab in Patients With Relapsed/Refractory Classical Hodgkin Lymphoma
New Findings in Hematology: Independent Conference Coverage of ASH 2016*; December 3-6, 2016; San Diego, California
*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, Celgene Corporation, Incyte, Merck, and Seattle Genetics.

2. KEYNOTE-087: Background
Pts with cHL commonly overexpress PD-1 ligands PD-L1 and PD-L2[1]
Increased PD-1 signaling reduces antitumor immune response by reversibly inhibiting T-cell activity
Pembrolizumab: humanized anti–PD-1 mAb[2]
Phase Ib study of pembrolizumab observed CR/PR in 20 of 31 (65%) patients with R/R cHL[3]
Current KEYNOTE-087 phase II study evaluated efficacy and safety of pembrolizumab in patients with R/R cHL[4]
cHL, classical Hodgkin lymphoma; R/R, relapsed/refractory.
1. Roemer MG, et al. J Clin Oncol. 2016;34: Garon EB, et al. N Engl J Med. 2015;372: Armand P, et al. J Clin Oncol. 2016;[Epub ahead of print]. 4. Moskowitz CH, et al. ASH Abstract 1107.
Slide credit: clinicaloptions.com

3. KEYNOTE-087: Phase II Study Design
Key inclusion criteria
Patients with R/R cHL
ECOG PS ≤ 1
3 cohorts defined by R/R cHL history
Cohort 1: progression after ASCT and subsequent brentuximab vedotin (BV; n = 69)
Cohort 2: failed salvage chemotherapy, ASCT ineligible, failed BV therapy (n = 81)
Cohort 3: failed ASCT, no BV after transplantation (n = 60)
Treatment: pembrolizumab 200 mg Q3W
Primary endpoint: ORR by blinded independent central review
Secondary endpoints: ORR by investigator review, DoR, PFS, OS
Responses determined with Revised Response Criteria for Malignant Lymphoma
CT scans Q12W
PET on Wks 12 and 24 and as clinically indicated
ASCT, autologous stem cell transplantation; BV, brentuximab vedotin; cHL, classical Hodgkin lymphoma; DoR, duration of response; ECOG, Eastern Cooperative Oncology Group; PS, performance status; R/R, relapsed/refractory.
Slide credit: clinicaloptions.com
Moskowitz CH, et al. ASH Abstract 1107.

4. KEYNOTE-087: Baseline Characteristics
Cohort 1 (n = 69)
Cohort 2 (n = 81)
Cohort 3 (n = 60)
Median age, yrs (range)
34 (19-64)
40 (20-76)
32 (18-73)
Previous lines of therapy
≥ 3, n (%)
< 3, n (%)
Median (range)
68 (99) 1 (1)
4 (2-12)
78 (96)
3 (4)
4 (1-11)
36 (60)
24 (40)
3 (2-10)
R/R after ≥ 3 lines of therapy, n (%)
69 (100)
81 (100)
60 (100)
Prior BV use
25 (42)
Previous radiation
31 (45)
21 (26)
BV, brentuximab vedotin; R/R, relapsed/refractory.
Slide credit: clinicaloptions.com
Moskowitz CH, et al. ASH Abstract 1107.

5. KEYNOTE-087: Overall Response Rate
Response, n (%)
Cohort 1 Assessed by BICR (n = 69)
Cohort 2 Assessed by BICR (n = 81)
Cohort 3 Assessed by BICR (n = 60)
All Pts Assessed by BICR (N = 210)
All Pts Assessed by Investigators (N = 210)
ORR
CR* PR
51 (73.9)
15 (21.7)
36 (52.2)
52 (64.2)
20 (24.7)
32 (39.5)
42 (70.0)
12 (20.0)
30 (50.0)
145 (69.0)
47 (22.4)
98 (46.7)
143 (68.1)
63 (30.0)
80 (38.1) SD
11 (15.9)
10 (12.3)
10 (16.7)
31 (14.8)
40 (19.0) PD
5 (7.2)
17 (21.0)
8 (13.3)
30 (14.3)
23 (11.0)
Undetermined
2 (2.9)
2 (2.5)
4 (1.9)
BICR, blinded independent central review; PD, progressive disease; SD, stable disease.
*In pts negative on PET, residual mass was permitted.
Slide credit: clinicaloptions.com
Moskowitz CH, et al. ASH Abstract 1107.

6. KEYNOTE-087: Overall Response Rate by Patient Subgroup
Subgroups analyzed by BICR
Response, n (%)
Pts With Primary Refractory Disease* (n = 73)
Pts Relapsed After ≥ 3 Lines of Therapy* (n = 146)
ORR CR PR
58 (79.5)
17 (23.3)
41 (56.2)
99 (67.8)
21 (21.2)
68 (46.6) SD
4 (5.5)
24 (16.4) PD
8 (11.0)
20 (13.7)
Undetermined
3 (4.1)
3 (2.1)
BICR, blinded independent central review; PD, progressive disease; SD, stable disease.
*Subgroups were not mutually exclusive.
Slide credit: clinicaloptions.com
Moskowitz CH, et al. ASH Abstract 1107.

7. KEYNOTE-087: Pembrolizumab Exposure and Duration of Response
Parameter
Cohort 1
Cohort 2
Cohort 3
All Pts
Median no. treatment cycles (range)
13 (1-21)
12 (1-21)
12.5 (3-21)
Median time to response, mos (range)
2.7 ( )
2.8 ( )
2.8 ( )
2.8 ( )
Response duration ≥ 6 mos, %
82.2 70
75.6
75.6*
*Estimate potentially biased because only 1 pt remained at risk after 9 mos.
93% of all pts had reduced tumor size assessed by BICR after median follow-up of mos (range: )
Treatment ongoing in 57% of pts
BICR, blinded independent central review.
Slide credit: clinicaloptions.com
Moskowitz CH, et al. ASH Abstract 1107.

8. KEYNOTE-087: Treatment-Related AEs
Any-Grade AEs in ≥ 5% of Pts, n (%)
All Pts (N = 210)
Hypothyroidism
26 (12.4)
Pyrexia
22 (10.5)
Fatigue
19 (9.0)
Rash
16 (7.6)
Diarrhea
15 (7.1)
Headache
13 (6.2)
Nausea
12 (5.7)
Cough
Neutropenia
11 (5.2)
AEs, n (%)
All Pts (N = 210)
Any-grade grade 3/4 AE
23 (11)
Grade 3 AEs in ≥ 2 pts
Neutropenia
Diarrhea
Dyspnea
5 (2.4)
2 (1.0)
AEs of interest in ≥ 2 pts
Grade 1/2 infusion-related reactions
Grade 2 pneumonitis
Grade 1/2 hyperthyroidism
Grade 2/3 colitis
Grade 2/3 myositis
10 (4.8)
6 (2.9)
AE, adverse event.
9 pts discontinued because of treatment-related AEs
No treatment-related deaths (2 deaths on study)
Slide credit: clinicaloptions.com
Moskowitz CH, et al. ASH Abstract 1107.

9. KEYNOTE-087: Conclusions
Pembrolizumab is highly active in R/R cHL with an ORR of 69% by BICR
Pts with primary refractory cHL: ORR of 80% (CR of 25%)
Pts with transplant-ineligible cHL secondary to failure of salvage therapy and BV: ORR of 64% (CR of 23%)
No new or unexpected adverse events reported
KEYNOTE-204 phase III trial initiated to compare pembrolizumab vs BV in pts with R/R cHL (NCT )
BICR, blinded independent central review; BV, brentuximab vedotin; cHL, classical Hodgkin lymphoma; R/R, relapsed/refractory.
Slide credit: clinicaloptions.com
Moskowitz CH, et al. ASH Abstract 1107.

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