Inotuzumab Ozogamicin (IO; CMC544), a CD22 Monoclonal Antibody Attached to Calicheamycin, Produces Complete Response (CR) plus Complete Marrow Response.

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Inotuzumab Ozogamicin (IO; CMC544), a CD22 Monoclonal Antibody Attached to Calicheamycin, Produces Complete Response (CR) plus Complete Marrow Response of > 50% in Refractory Relapse (R-R) Acute Lymphocytic Leukemia (ALL) Jabbour E et al. Proc ASCO 2011;Abstract 6507.

Study Design: Inotuzumab Ozogamicin (IO) in Refractory/Relapsed (R-R) ALL Eligibility (n = 48, closed): –Refractory or relapsed CD22-positive ALL –≥ 16 yrs in first 10 patients; children were allowed in the study after safety was established Dosing: IO at 1.8 mg/m 2 IV over 1 hour q3-4 wks in all patients except 6 who received 1.3 mg/m 2 IV over 1 hour during the first course. Patients with objective response were allowed 8 cycles of treatment. If stable or no response after 2 courses of treatment, rituximab was added at 375 mg/m 2 D1. Jabbour E et al. Proc ASCO 2011;Abstract 6507.

Patient Characteristics (N = 48) Characteristic CategoryN (%) Age ≤ 18 yrs ≥ 60 yrs 3 (6) 12 (25) Salvage status S1 S2 ≥ S3 10 (21) 24 (50) 12 (25) Prior HCVAD regimenYes28 (58) Prior allo SCTYes7 (15) % CD22-positive > (56) 14 (29) 7 (15) Jabbour E et al. Proc ASCO 2011;Abstract 6507.

IO in R-R ALL: Response (N = 46*) Response No (%) Objective response28 (61) CR (complete remission) CRp CRi (marrow CR) Partial response 9 (20) 14 (30) 5 (11) 0 Resistant Death < 4 wks 18 (39) 2 (4) * 2 patients too early to evaluate CRp = complete remission with incomplete platelet recovery CRi = complete remission with incomplete blood count recovery Jabbour E et al. Proc ASCO 2011;Abstract 6507.

IO in R-R ALL: Cytogenetic Response in Abnormal Karyotype CRp = complete remission with incomplete platelet recovery CRi = complete remission with incomplete platelet or neutrophil recovery Jabbour E et al. Proc ASCO 2011;Abstract Cytogenetic Response, n (%) Subgroup, patientsCompletePartial Abnormal karyotype and morphologic response, n = (88%)— Complete response (CR), n = 6 5 (83%)1 (17%) CRp, n = 8 8 (100%)— CRi, n = 4 3 (75%)— All patients with abnormal karyotype, n = (47%)—

Efficacy of IO in R-R ALL Compared to Standard Chemotherapy* Parameter % Overall Response Rate p-value Inotuzumab (n = 48) Chemotherapy (n = 459) Overall 6132<0.001 Salvage Salvage ≥ Salvage 36713<0.001 * Historical data from MD Anderson Cancer Center Jabbour E et al. Proc ASCO 2011;Abstract 6507.

IO in R-R ALL: Response by IO Level in Plasma 3 Hr After End of Infusion (EOI) With permission from Jabbour E et al. Proc ASCO 2011;Abstract Response = 89% for plasma level >100 ng/ml versus 33% for plasma level <100 ng/ml at 3 hr post EOI, p-value = CR CRI CRP FAIL Response Inotuzumab Plasma Levels 3 Hour (ng/mL) Median

IO in R-R ALL: Adverse Events Adverse events (n) Grade 1-2Grade 3-4 Drug fever 199 Hypotension12 (4 with fever)1 LFT abnormalities Bilirubin SGPT/SGOT Lipase/amylase01 Veno-occlusive disease—4 (post ASCT) Periportal fibrosis2 (C1D38, C4D45) Jabbour E et al. Proc ASCO 2011;Abstract 6507.

Author Conclusions IO demonstrated very high response rate (ORR = 61%) for single-agent therapy in R-R ALL. There is correlation of response with drug plasma levels. Toxicities include thrombocytopenia (data not shown) and abnormalities of LFTs. Plans include the assessment of IO administered at alternative schedules (weekly) and studies on combinations of IO with chemotherapy. Jabbour E et al. Proc ASCO 2011;Abstract 6507.