1. KEYNOTE-086 (Cohort A): Phase II Evaluation of Pembrolizumab Monotherapy in Heavily Pretreated Metastatic TNBC
CCO Independent Conference Highlights* of the 2017 ASCO Annual Meeting; June 2-6, 2017; Chicago, Illinois
*Clinical Care Options (CCO) is an independent medical education organization that provides conference coverage and other unique educational programs for healthcare professionals
TNBC, triple-negative breast cancer.
This activity is supported by educational grants from AbbVie, Amgen, AstraZeneca, Celgene Corporation, Genentech, Halozyme, Incyte, and Merck & Co., Inc.

2. KEYNOTE-086 (Cohort A): Background
TNBC is a heterogenous disease with poor prognosis, high unmet need[1-3]
Chemotherapy is SoC, with significant toxicity and median OS < 1 yr
Pembrolizumab: humanized anti–PD-1 mAb[1,4]
In phase Ib KEYNOTE-021 study, clinical activity, acceptable safety observed in pts with pretreated, PD-L1+ mTNBC
KEYNOTE-086: phase II multicohort study evaluating safety, activity of pembrolizumab monotherapy in mTNBC[1]
Current report on cohort A: previously treated mTNBC, PD-L1+ or PD-L1-
Cohort B: previously untreated mTNBC, PD-L1+
m, metastatic; SoC, standard of care; TNBC, triple-negative breast cancer.
1. Adams S, et al. ASCO Abstract den Brok, WD, et al. Breast Cancer Res Treat. 2017;161: Li X, et al. Breast Cancer Res Treat. 2017;161: Nanda R, et al. J Clin Oncol. 2016;34:
Slide credit: clinicaloptions.com

3. KEYNOTE-086 (Cohort A): Study Design
International, multicohort phase II study
mTNBC pts who progressed on ≥ 1 prior systemic therapy;
ECOG PS 0-1; LDH < 2.5 x ULN; tumor biopsy sample available for PD-L1 evaluation
(N = 170)
For 2 yrs or until PD, unacceptable toxicity, consent withdrawal, or investigator decision
Pembrolizumab
200 mg IV Q3W
(N = 170)
Endpoints
Primary: ORR in overall, PD-L1+ pts; safety
Secondary: DoR, DCR, PFS, OS in overall, PD-L1+ pts
Assessments
Tumor imaging: every 9 wks for 1 yr, then every 12 wks
Response: RECIST v1.1 by ICR
PD-L1 positive: CPS ≥ 1% by IHC at central lab
CPS, combined positive score; DCR, disease control rate; DoR, duration of response; ECOG, Eastern Cooperative Oncology Group; ICR, independent central review; LDH, lactate dehydrogenase; mTNBC, metastatic triple-negative breast cancer; PD, progressive disease; PS, performance status; RECIST, Response Evaluation Criteria in Solid Tumors; ULN, upper limit of normal.
Slide credit: clinicaloptions.com
Adams S, et al. ASCO Abstract 1008.

4. KEYNOTE-086 (Cohort A): Baseline Characteristics
All Pts
(N = 170*)
PD-L1 Positive
(n = 105)
PD-L1 Negative
(n = 64)
Median age, yrs (range)
53.5 (28-85)
53.0 (30-85)
55.0 (28-80)
Female, %
100
ECOG PS 1, %
47.1
51.4
40.6
LDH > 1 x ULN
51.2
48.6
56.2
Postmenopausal, %
82.4
81.0
84.4
Visceral ± nonvisceral disease, %
Prior taxane, anthracycline, %
95.9
97.1
93.8
Prior (neo)adjuvant therapy, %
83.5
81.9
85.9
Prior lines of therapy, % 1 2
≥ 3
31.2
25.3
43.5
34.3
25.7
40.0
26.6
23.4
50.0
ECOG, Eastern Cooperative Oncology Group; LDH, lactate dehydrogenase; PS, performance status; ULN, upper limit of normal.
*n = 1 pt with unknown PD-L1 status.
Slide credit: clinicaloptions.com
Adams S, et al. ASCO Abstract 1008.

5. KEYNOTE-086 (Cohort A): Best Overall Response
All Pts
(N = 170†)
PD-L1 Positive
(n = 105)
PD-L1 Negative
(n = 64)
ORR, % (95% CI)
4.7 ( )
4.8 ( )
4.7 ( )
DCR,‡ % (95% CI)
7.6 ( )
9.5 ( )
Best overall response, % CR PR SD PD
0.6
4.1
20.6
60.6
1.0
3.8
21.0
62.9
4.7
18.8
57.8
Median TTR, mos (range)
3.0 ( ) --
Median DoR, mos (range)
6.3 (1.2+ to 10.3+)
DCR, disease control rate; DoR, duration of response; LDH, lactate dehydrogenase; PD, progressive disease; SD, stable disease; TTR, time to response; ULN, upper limit of normal.
*Median follow-up: 10.9 mos. †n = 1 pt with unknown PD-L1 status. ‡DCR = SD ≥ 24 wks + CR + PR.
Numerically lower ORR in poor prognosis pt subgroups: LDH > ULN, ≥ 3 metastatic organ sites, liver metastases, visceral disease
Slide credit: clinicaloptions.com
Adams S, et al. ASCO Abstract 1008.

6. KEYNOTE-086 (Cohort A): Survival
Outcome
All Pts
(N = 170*)
PD-L1 Positive
(n = 105)
PD-L1 Negative
(n = 64)
PFS
Median, mos (95% CI)
Events, n
3-mo rate, %
6-mo rate, %
2.0 ( )
148
25.5
12.3
2.0 ( ) 90
24.2
13.2
1.9 ( ) 57
26.6
11.1 OS
9-mo rate, %
8.9 ( )
69.0
49.8
8.3 ( ) 58
71.0
47.5
10.0 (6.2-NR) 32
65.4
52.6
LDH, lactate dehydrogenase; NR, not reportable.
*n = 1 pt with unknown PD-L1 status.
Slide credit: clinicaloptions.com
Adams S, et al. ASCO Abstract 1008.

7. KEYNOTE-086 (Cohort A): OS By Best Overall Response20 40 60 80
100 2 4 6 8 9 10 12 14 16
Mos
OS (%)
Pts at risk, n 35
103 94
CR or PR SD PD 72 33 63 29 39 7 1
Response
CR or PR SD PD
Events/Pt, n/n
0/8
6/35
66/103
mPFS, Mos (95% CI)
Not reached (NR-NR)
Not reached (12.7-NR)
7.1 ( )
6-Mo PFS, %
100
64.6
9-Mo PFS, %
100
89.6
39.0
NR, not reportable; PD, progressive disease; mPFS, median PFS; SD, stable disease.
Slide credit: clinicaloptions.com
Adams S, et al. ASCO Abstract Reproduced with permission.

8. KEYNOTE-086 (Cohort A): Safety
No deaths due to AEs
Treatment-related and immune-related AEs led to discontinuation of pembrolizumab in 4.1% and 1.2% of pts, respectively
AEs in ≥ 5% of Pts, %
Any Grade
(N = 170)
Grade 3/4
Treatment related
Fatigue
Nausea
Decreased appetite
Hypothyroidism
Diarrhea
Asthenia
Arthralgia
Pruritus
60.0
20.6
10.6
7.6
7.1
6.5
5.9
12.4
0.6
1.8
Immune mediated
Hyperthyroidism
Pneumonitis
18.8
11.2
4.7
3.5
1.2
AE, adverse event.
Slide credit: clinicaloptions.com
Adams S, et al. ASCO Abstract 1008.

9. KEYNOTE-086 (Cohort A): Conclusions
Pembrolizumab monotherapy generated durable responses in a subset of pts with pretreated mTNBC
Responses seem to be independent of PD-L1 expression
Lower numerical ORR in pts with factors for poor prognosis
Treatment well tolerated with manageable safety profile
Investigators note promising preliminary survival results, especially in pts with SD or better
Randomized studies of pembrolizumab monotherapy and combination therapy under way in TNBC
m, metastatic; SD, stable disease; TNBC, triple-negative breast cancer.
Slide credit: clinicaloptions.com
Adams S, et al. ASCO Abstract 1008.

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