1. ALCANTARA: Blinatumomab Shows Activity in R/R Ph-Positive B-Precursor ALL
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.
ALL, acute lymphoblastic leukemia; Ph, Philadelphia chromosome; R/R, relapsed/refractory.
This program is supported by educational grants from Amgen, Celgene Corporation, Incyte, Merck, Seattle Genetics, and Takeda Oncology.

2. ALCANTARA: Background
Blinatumomab, a bispecific T-cell engaging antibody construct, has shown antileukemic activity in Ph- ALL
43% of pts achieved CR/CRh in first 2 cycles of blinatumomab monotherapy[1]
Pts with R/R Ph+ ALL have a poor overall prognosis despite improved outcomes from TKI therapy
Ph+ is the most common (25% of adult pts) cytogenetic abnormality in B-precursor ALL
Mutations in BCR-ABL lead to TKI resistance in some pts
ALCANTARA evaluated efficacy and safety of blinatumomab in pts with R/R Ph+ ALL resistant to TKI[2]
ALL, acute lymphoblastic leukemia; CRh, complete remission with partial hematologic recovery; Ph, Philadelphia chromosome; R/R, relapsed/refractory; TKI, tyrosine kinase inhibitor.
1. Topp MS, et al. Lancet Oncol. 2015;16: Martinelli G, et al. ASH Abstract 679.
Slide credit: clinicaloptions.com

3. ALCANTARA: Study Design
Phase II single arm study
Primary endpoint: CR/CRh during first 2 cycles
Secondary endpoints: best CR, MRD, RFS, OS, allogeneic HSCT rate, and safety
Primary Endpoint Assessed During First 2 Cycles
Adults with R/R Ph+ B-precursor ALL; ECOG PS 0-2; > 5% BM blasts; failed TKI
(N = 45)
Blinatumomab IV
9 µg/day x 1wk
28 µg/day x 3 wks (cycle 1) 28 µg/day x 4 wks (cycle 2)
(4 wks on, 2 wks off)
Consolidation:
Blinatumomab IV
28 µg/day x 4 wks
≤ 3 cycles
(4 wks on, 2 wks off)
Follow-up at 30 days and ≤ 18 mos
ALL, acute lymphoblastic leukemia; BM, bone marrow; CRh, complete remission with partial hematologic recovery; ECOG, Eastern Cooperative Oncology Group; HSCT, hematopoietic stem cell transplantation; MRD, minimal residual disease; Ph, Philadelphia chromosome; PS, performance status; RFS, relapse-free survival; R/R, relapsed/refractory; TKI, tyrosine kinase inhibitor.
Slide credit: clinicaloptions.com
Martinelli G, et al. ASH Abstract 679. ClinicalTrials.gov. NCT

4. ALCANTARA: Baseline Characteristics
Pts (N = 45)
Median age, yrs (range)
55 (23-78)
Male, n (%)
24 (53)
Prior relapses, n (%)
0 (primary refractory) 1 2
≥ 3
3 (7)
25 (56)
13 (29)
4 (9)
Prior allogeneic HSCT, n (%)
20 (44)
Prior TKI, n (%)
All pts
Imatinib
Dasatinib
Nilotinib
Ponatinib
45 (100)
39 (87)
16 (36)
23 (51)
BM blasts, n (%)
< 50%
≥ 50%
11 (24)
34 (76)
ABL kinase domain mutations,* n (%)
17 (46)
T3151 mutation
10 (27)
ALL, acute lymphoblastic leukemia; BM, bone marrow; HSCT, hematopoietic stem cell transplantation; TKI, tyrosine kinase inhibitor.
*n = 37
Slide credit: clinicaloptions.com
Martinelli G, et al. ASH Abstract 679.

5. ALCANTARA: Efficacy Median RFS: 6.7 mos (95% CI: 4.4-NE)
Parameter
Response, %
Primary endpoint
CR/CRh (first 2 cycles)
T315l mutation
≥ 2 prior 2+ gen TKI
Prior ponatinib treatment 36 40 41 35
Secondary endpoints
Best response (first 2 cycles) CR
CRh
CRi (not including CRh) 31 4
Complete MRD response*
MRD response in pts with ABL-kinase mutations 88
100
Proceeded to allogeneic HSCT 25
ALL, acute lymphoblastic leukemia; CRh, complete remission with partial hematologic recovery; CRi, complete response incomplete; HSCT, hematopoietic stem cell transplantation; MRD, minimal residual disease; NE, not estimable; RFS, relapse-free survival; TKI, tyrosine kinase inhibitor.
*Includes all 4 CR/CRh T315I pts.
Median RFS: 6.7 mos (95% CI: 4.4-NE)
Median OS: 7.1 mos (95% CI: 5.6-NE)
Slide credit: clinicaloptions.com
Martinelli G, et al. ASH Abstract 679.

6. ALCANTARA: Safety AE, n (%) (N = 45) Treatment Emergent
Treatment Related
Overall
Worst grade < 3
Worst grade ≥ 3
Worst grade 5 (death)
8 (18)
37 (82)
5 (11)
21 (47)
20 (44)
1 (2)
Grade ≥ 3 in ≥ 5% pts
Febrile neutropenia
Thrombocytopenia
Anemia
Increased ALT
Increased AST
Pyrexia
Pain
Sepsis
Leukocytosis
Neutropenia
Device-related infection
Headache
12 (27)
10 (22)
7 (16)
4 (9)
3 (7)
0 (0)
2 (4)
AE, adverse event; ALT, alanine aminotransferase; AST, aspartate aminotransferase.
Neurologic events: any grade, n = 21 (47%); grade 3, n = 3 (7%); no grade 4. Cytokine release syndrome: any grade, n = 4 (9%); no grade 3 or 4.
Slide credit: clinicaloptions.com
Martinelli G, et al. ASH Abstract 679.

7. ALCANTARA: Conclusions
Blinatumomab achieved antileukemic activity in Ph+ R/R ALL pts with poor prognosis and previous failure of TKI therapy
CR/CRh rate: 36%
Response to therapy was independent of T315l mutation
100% of responders with ABL-kinase domain mutations had complete MRD response
Median OS: 7.1 mos
Safety profile consistent with blinatumomab treatment of pts with Ph- R/R ALL
ALL, acute lymphoblastic leukemia; CRh, complete remission with partial hematologic recovery; MRD, minimal residual disease; Ph, Philadelphia chromosome; R/R, relapsed/refractory.
Slide credit: clinicaloptions.com
Martinelli G, et al. ASH Abstract 679.

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