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.

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;14:2775-2784. 2. Collins SM, et al. Cancer Immunol Immunother. 2013;62:1841-1849. 3. Guo H, et al. Mol Cell Biol. 2015;35:41-51. 4. Richardson PG, et al. ASH 2014. Abstract 302. 5. Lonial S, et al. ASCO 2015. Abstract 8508.

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 1-21 + 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 1-21 + 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 2015. Abstract 8508.

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 2015. Abstract 8508.

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 (0.57-0.85) 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 2015. Abstract 8508.

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 2015. Abstract 8508.

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 2015. Abstract 8508.

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