1. ELOQUENT-2: Addition of Elotuzumab to Len/Dex Extends PFS in Relapsed/Refractory Myeloma CCO Independent Conference Highlights of the 2015 ASCO Annual Meeting*
May 29 - June 2, 2015
*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.
Dex, dexamethasone; Len, lenalidomide; PFS, progression-free survival.
This program is supported by educational grants from AstraZeneca, Bayer, Bristol-Myers Squibb, Celgene Corporation, Genentech, Incyte, and Novartis.

2. ELOQUENT-2: Background
Elotuzumab: a humanized IgG1 monoclonal antibody directed against SLAMF7 with dual mechanism of action[1]
Targets SLAMF7 expressed on NK cells; binding causes direct cell activation in NK cells but not MM cells[2,3]
Tags surface of malignant plasma cells and targets them for recognition, inducing apoptosis through activated NK cells[2]
Phase Ib/2 study showed high response rates and PFS benefit with elotuzumab + lenalidomide/dexamethasone in R/R MM[4]
Granted breakthrough therapy designation in R/R MM
Phase III trial undertaken to further evaluate the combination in R/R MM[5]
MM, multiple myeloma; NK, natural killer; PFS, progression-free survival; R/R, relapsed/refractory.
1. Hsi ED, et al. Clin Cancer Res. 2008;14: Collins SM, et al. Cancer Immunol Immunother. 2013;62: Guo H, et al. Mol Cell Biol. 2015;35: Richardson PG, et al. ASH Abstract Lonial S, et al. ASCO Abstract 8508.

3. ELOQUENT-2: Study Design
Randomized, open-label, multicenter international phase III trial
Primary endpoints: PFS, ORR
Secondary endpoints: OS (data not mature), DoR, QoL, safety
Elotuzumab* 10 mg/kg IV
QW in cycles 1, 2; q2w thereafter +
Lenalidomide 25 mg PO Days
Dexamethasone 40 mg/wk equiv
28-day cycles
(n = 321)
R/R MM with 1-3 prior lines of therapy (prior lenalidomide exposure allowed in 10%)
(N = 646)
Assessed q4w until PD; followed q12w thereafter for survival
Lenalidomide 25 mg PO Days
Dexamethasone 40 mg PO Days 1, 8, 15, 22; 28-day cycles
(n = 325)
DoR, duration of response; equiv, equivalent; MM, multiple myeloma; ORR, overall response rate; OS, overall survival; PD, progressive disease; PFS, progression-free survival; PO, orally; QW, once weekly; q2w, every 2 weeks; q4w, every 4 weeks; q12w, every 12 weeks; QoL, quality of life; R/R, relapsed/refractory.
*Premedication administered before elotuzumab.
Lonial S, et al. ASCO Abstract 8508.

4. ELOQUENT-2: Pt Characteristics
Elo-Rd (n = 321)
Rd (n = 325)
Median age, yrs (range)
67 (37-88)
66 (38-91)
ISS stage, %
I/II/III
44/32/21
43/32/21
Cytogenetics (FISH), %
del(17p)
t(4;14)
1q21 32 9 46 10 50
Median prior regimens, n (range)
2 (1-4)
Prior therapies, %
Bortezomib
Melphalan
Thalidomide
Lenalidomide 68 69 48 5 71 61 7
Refractory to most recent therapy, % 35
Prior SCT, % 52 57
Elo, elotuzumab; ISS, International Staging System; FISH, fluorescence in situ hybridization; Rd, lenalidomide/dexamethasone; SCT, stem cell transplantation.
Lonial S, et al. ASCO Abstract 8508.

5. ELOQUENT-2: Efficacy
Significant PFS benefit with elotuzumab maintained over time
Similar PFS benefit across subgroups, including older pts, and pts with and without high-risk cytogenetics, del(17p), t(4;14)
Among pts with a similar depth of response (eg, PR or CR), a higher proportion of those given Elo-Rd had PFS at 1 and 2 yrs vs Rd
Parameter
Elo-Rd (N = 321)
Rd (n = 325)
P Value
Median PFS, mos
19.4
14.9
.0004
HR (95% CI)
0.70 ( )
1-year PFS, % 68 57
2-year PFS, % 41 27
ORR
CR (sCR + CR)
VGPR PR 79 4* 28 46 66 7* 21 38
.0002
Elo, elotuzumab; CBR, clinical benefit rate; CR, complete response; Ld, lenalidomide/dexamethasone; OS, overall survival; PFS, progression-free survival; PR, partial response; sCR, stringent complete response; VGPR, very good partial response.
*Interference from elotuzumab on immunofixation assay likely resulted in underestimate of CR rate.
Lonial S, et al. ASCO Abstract 8508.

6. ELOQUENT-2: Safety
Elotuzumab well tolerated, had no negative effect on QoL
Infusion reactions reported in 10% of pts (9% grade 1/2; 1% grade 3); 70% occurred with initial dose
2 discontinuations (1%) due to infusion reaction
Selected Grade 3/4 AEs, %
Elo-Ld (n = 318)
Ld (n = 317)
Lymphopenia 77 49
Neutropenia 34 44
Infection
28*
24*
Nonhematologic
Fatigue
Pyrexia
Diarrhea 9 3 5 8 4
AE, adverse event; QoL, quality of life; Elo, elotuzumab; Ld, lenalidomide/dexamethasone.
*Incidence similar after controlling for duration of therapy.
Lonial S, et al. ASCO Abstract 8508.

7. ELOQUENT-2: Investigator Conclusions
Addition of elotuzumab to lenalidomide/dexamethasone associated with statistically and clinically significant increase in PFS, ORR in pts with R/R MM
PFS benefit with elotuzumab maintained across important subgroups, including high-risk and elderly pts
Adding elotuzumab did not increase the incidence of AEs and without a negative effect on QoL
OS data not yet mature
Investigators noted elotuzumab is first monoclonal antibody to show PFS benefit when added to lenalidomide/dexamethasone in randomized, phase III trial in R/R MM
AE, adverse event; MM, multiple myeloma; PFS, progression-free survival; ORR, overall response rate; OS, overall survival; QoL, quality of life; R/R, relapsed/refractory.
Lonial S, et al. ASCO Abstract 8508.

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