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.

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;16:57-66. 2. Martinelli G, et al. ASH 2015. Abstract 679. Slide credit: clinicaloptions.com

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 2015. Abstract 679. ClinicalTrials.gov. NCT02000427.

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 2015. Abstract 679.

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 2015. Abstract 679.

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 2015. Abstract 679.

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 2015. Abstract 679.

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