1. KEYNOTE-023: Pembrolizumab + Lenalidomide + Dexamethasone Shows Promising Activity and Safety in R/R MM
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.
MM, multiple myeloma; R/R, relapsed/refractory.
This activity is supported by educational grants from Amgen, Ariad, Bayer Healthcare Pharmaceuticals, Celgene Corporation, Genentech, Incyte, Merck, and Taiho Pharmaceuticals.

2. KEYNOTE-023: Study Background
IMiDs exert dual mechanisms of action that result in tumoricidal and immunomodulatory effects
Pembrolizumab: anti–PD-1 antibody restores antitumor T-cell function
Increased PD-1 expression in T-cells of pts with MRD/R/R MM[1]
Combining IMiDs and PD-L1 blockade may result in synergistic antimyeloma activity
KEYNOTE-023: phase I dose-escalation and -expansion study evaluating safety and efficacy of pembrolizumab + lenalidomide + low-dose dexamethasone in pts with R/R MM[2]
Pts had to have failed ≥ 2 prior regimens, including a proteasome inhibitor and an IMiD
IMiDs, immunomodulatory drugs; MM, multiple myeloma; MRD, minimal residual disease; R/R, relapsed/refractory.
1. Liu J, et al. Blood. 2007;110: Mateos MV, et al. ASCO Abstract 8010.
Slide credit: clinicaloptions.com

3. KEYNOTE-023: Study Design
Treatment doses tested
Pembrolizumab: 2 mg/kg or 200 mg IV Q2W
Lenalidomide: 10 or 25 mg
Dexamethasone: 40 mg
Final MTD: pembrolizumab 200 mg IV Q2W + lenalidomide 25 mg + dexamethasone 40 mg
Primary endpoints: safety, tolerability
Secondary endpoints: ORR, DoR, PFS, OS
Safety analysis included all pts (N = 51); efficacy analysis included pts who completed 3 cycles or discontinued due to PD (n = 40)
Median pt follow-up: 9 mos
DoR, duration of response; MTD, maximum tolerated dose; PD, progressive disease.
Slide credit: clinicaloptions.com
Mateos MV, et al. ASCO Abstract 8010.

4. KEYNOTE-023: Baseline Characteristics
Pembrolizumab + Lenalidomide + Dexamethasone (N = 51)
Median age, yrs (range)
61 (46-77)
Male, % 65
ECOG PS 0 / 1, %
22/77
LDH ≤ 400 IU/mL, % 57
β-2 microglobulin < 3.5 mg/L, %
Median prior therapies (range)
≥ 5 prior lines, %
4 (1-10) 39
Prior ASCT, % 86
Refractory to lenalidomide, % 75
Refractory to bortezomib, % 63
Refractory to last line of therapy, %
Refractory to lenalidomide as last line, % 78 20
ASCT, autologous stem cell transplant; ECOG, Eastern Cooperative Oncology Group; LDH, lactate dehydrogenase; PS, performance status.
Slide credit: clinicaloptions.com
Mateos MV, et al. ASCO Abstract 8010.

5. KEYNOTE-023: Treatment-Related AEs
Treatment-Related AEs Occurring in ≥ 15% (N = 51)
All Grades, %
Grade 3-5, %
All 94 65
Thrombocytopenia 41 18
Neutropenia 37 33
Diarrhea 28
Fatigue 26 2
Anemia 22 12
Hyperglycemia 8
Myalgia 16
2 deaths (4%) due to treatment-related AEs
Hepatic failure tied to veno-occlusive disease related to combination
Ischemic stroke related to lenalidomide
3 pts (6%) discontinued treatment due to treatment-related AEs
AE, adverse event.
Slide credit: clinicaloptions.com
Mateos MV, et al. ASCO Abstract 8010.

6. KEYNOTE-023: Immune-Related AEs
No dose modification or treatment discontinuation required for management of immune-related AEs
No reported cases of pneumonitis or colitis
No reported infusion reactions
Immune-Related AEs (N = 51) %
Hyperthyroidism, grade 1 2
Hypothyroidism, grade 1 4
Thyroiditis, grade 1
Increased transaminases, grade 3
Renal failure, grade 3
AE, adverse event.
Slide credit: clinicaloptions.com
Mateos MV, et al. ASCO Abstract 8010.

7. KEYNOTE-023: Response Rates
88% of pts showed some decrease in M protein or free light chains from baseline
Best Overall Response, %
Efficacy Population
(n = 40)
Len-Refractory Population
(n = 29)
ORR
Stringent CR
VGPR PR 50 3 13 35 38 10 24 SD 48 59
Disease control rate (CR + PR + SD) 98 97 PD
Len, lenalidomide; PD, progressive disease; SD, stable disease; VGPR, very good PR.
Slide credit: clinicaloptions.com
Mateos MV, et al. ASCO Abstract 8010.

8. KEYNOTE-023: Response Duration
Among efficacy-evaluable population (n = 40):
Median DoR: 11.3 mos
Median time to first OR: 1.5 mos (range: mos)
4 pts who responded had improvement in quality of response
75% of pts still alive at time of data cutoff
Among total study population (N = 51):
12 pts (24%) still receiving treatment
39 pts (76%) discontinued treatment due to PD (n = 28), AEs (n = 3), withdrawal (n = 3), physician decision (n = 4), noncompliance (n = 1)
AEs, adverse events; DoR, duration of response; PD, progressive disease.
Slide credit: clinicaloptions.com
Mateos MV, et al. ASCO Abstract 8010.

9. KEYNOTE-023: Conclusions
MTD established as pembrolizumab 200 mg + lenalidomide mg + dexamethasone 40 mg in R/R MM[1]
Treatment combination showed an acceptable safety and tolerability profile
Consistent with AEs observed with pembrolizumab in solid tumors
Immune-related AEs uncommon
Robust activity demonstrated in heavily pretreated pts with R/R MM; investigators suggest results support continued development of pembrolizumab in MM
Phase III studies of pembrolizumab in MM initiated (KEYNOTE and KEYNOTE-183)[2,3]
AEs, adverse events; MTD, maximum tolerated dose; MM, multiple myeloma; R/R, relapsed/refractory.
1. Mateos MV, et al. ASCO Abstract ClinicalTrials.gov. NCT 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