1. Phase Ib MMY1001: Daratumumab Plus Pom/Dex for Patients With R/R MM
New Findings in Hematology: Independent Conference Coverage* of ASH 2015, December 5-8, 2015, Orlando, Florida
*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; Pom/Dex, pomalidomide, dexamethasone; R/R, relapsed/refractory.
This program is supported by educational grants from Amgen, Celgene Corporation, Incyte, Merck; Seattle Genetics, and Takeda Oncology.

2. Daratumumab + Pom/Dex in R/R MM: Background
Daratumumab: anti-CD38 IgG1 MAb
Activity mediated by direct antitumor effects, ADCC and other immune-mediated apoptosis, and immunomodulation
Safe, active as single agent or in combination with Rd in R/R MM
Approved November 2015 for use in MM pts with ≥ 3 prior therapies
Potential synergy with pomalidomide + dexamethasone
Pomalidomide increases CD38 expression in MM cells[1]
Current phase Ib study sought to determine efficacy, safety of daratumumab plus pom/dex in heavily pretreated and highly refractory pts with R/R MM[2]
ADCC, antibody-dependent cell-mediated cytotoxicity; MM, multiple myeloma; Pom/Dex, pomalidomide, dexamethasone; Rd, lenalidomide/dexamethasone; R/R, relapsed/refractory.
1. Boxhammer R, et al. ASCO Abstract Chari A, et al. ASH Abstract 508.
Slide credit: clinicaloptions.com

3. Phase Ib MMY 1001: Study Design
Open-label, multicenter trial of daratumumab with various backbone therapies
Current analysis: daratumumab plus pomalidomide/dexamethasone
Treat 6 pts; if ≤ 1 DLT enroll additional 6 pts; followed by expansion
Primary endpoints: safety, tolerability
Secondary endpoint: ORR
Pts with R/R MM after ≥ 2 prior therapies including ≥ 2 cycles len/bort; no prior pom
(N = 98)
Daratumumab 16 mg/kg IV* +
Pomalidomide 4 mg Days
Dexamethasone 40 mg† Days 1,8,15,22
in 28-day cycles
Until PD
*QW cycles 1-2, Q2W cycles 3-6, Q4W cycles 7+. †20 mg in pts older than 75 yrs of age.
DLT, dose-limiting toxicity; len/bort, lenalidomide, bortezomib; MM, multiple myeloma; PD, progressive disease; pom, pomalidomide.
Slide credit: clinicaloptions.com
Chari A, et al. ASH Abstract 508. Reproduced with permission.

4. MMY1001: Baseline Characteristics
Daratumumab + Pom/Dex (N = 98)
Median age, yrs (range)
70 yrs or older, %
64.5 ( ) 29
Male, % 56
Median time since diagnosis, yrs (range)
5.2 ( )
Median no. prior therapies, n (range)
Prior ASCT, %
Prior PI, %
Bortezomib, %
Carfilzomib, %
Prior IMiD, %
4 (2-13) 75
100 98 32
Refractory to, % PI
Lenalidomide
PI + IMiD 76 66 30 89 67
ASCT, autologous stem cell transplantation; IMiD, immunomodulatory drug; PI, proteasome inhibitor; Pom/Dex, pomalidomide/dexamethasone.
Slide credit: clinicaloptions.com
Chari A, et al. ASH Abstract 508. Reproduced with permission.

5. MMY1001: Pt Disposition 61% of pts (n = 61) remain on treatment
39% of pts (n = 38) discontinued treatment
Due to PD: 19%
Due to AEs: 8%
Due to death: 5%
Due to investigator decision or refusal: 3%
AE, adverse event; PD, progressive disease.
Slide credit: clinicaloptions.com
Chari A, et al. ASH Abstract 508.

6. MMY1001: Pt Safety and Tolerability
No new safety signals with combination vs pom/dex alone
Grade ≥ 3 AE incidence similar to pom/dex
17 deaths on trial, mostly due to disease progression
46% pts required G-CSF and 25% required blood transfusions during treatment
Few grade ≥ 3 infusion-related reactions (6%)
Managed with premedication and reduced infusion rates
AEs in > 20%
of Pts, %
Pts (N = 98)
Any Grade
Grade ≥ 3
Any grade 97 91
Neutropenia 63 60
Anemia 42 25
Fatigue 41 8
Thrombocytopenia 34 15
Leukopenia 32 20
Cough 31
Diarrhea 30 1
Dyspnea 28 6
Nausea
Constipation 22
AE, adverse event; G-CSF, granulocyte-colony stimulating factor; pom/dex, pomalidomide/dexamethasone.
Slide credit: clinicaloptions.com
Chari A, et al. ASH Abstract 508. Reproduced with permission.

7. MMY1001: Efficacy Outcome Evaluable Pts (n = 75) ORR, % Stringent CR
VGPR PR 71 5 4 33 28 MR 3 SD 23
ORR in double-refractory pts, % 67
Median time to first response, mo
1.2
M-protein reduction ≥ 50% from baseline, % 77
6-mo PFS, % 66
MR, minor response; SD, stable disease; VGPR, very good PR.
Chari A, et al. ASH Abstract 508. Reprinted with permission.
Slide credit: clinicaloptions.com

8. MMY1001: Change in Paraprotein From Baseline
-25 25 50 75
-50
-75
-100
N = 75
Relative Change in Paraprotein From Baseline (%)
Urine M-protein
Serum M-protein
Free light chain
Chari A, et al. ASH Abstract 508. Reprinted with permission.
Slide credit: clinicaloptions.com

9. MMY1001: Conclusions
In early analysis, daratumumab plus pom/dex shows promising activity in heavily pretreated R/R MM
Rapid initial responses that are deepening over time
71% ORR overall; 67% ORR in pts double-refractory to PI/IMiD
Combination has tolerable safety profile similar to pom/dex alone
No new safety concerns
Authors conclude that these results support further study of this combination in phase III trial
IMiD, immunomodulatory drug; MM, myeloma; PI, proteasome inhibitor; pom/dex, pomalidomide, dexamethasone; R/R, relapsed/refractory.
Slide credit: clinicaloptions.com
Chari A, et al. ASH Abstract 508.

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