Inotuzumab: from preclinical development to success in B-cell acute lymphoblastic leukemia

Joseph Wynne, David Wright and Wendy Stock

Article Figures & Data


  • Table 1.

    Select trials in NHL identifierDiseaseInO scheduleNo. of patientsORR, % (CR, %)VODNotes
    Phase 1 MTD22R/R NHL0.4-2.4 mg/m2 once per cycle79391/79Determined MTD of 1.8 mg/m2
    Phase 123NCT00717925R/R Follicular NHL1.3-1.8 mg/m2 once per cycle1385 (54 CR)NoneTested in Japanese population
    Phase 1 combining InO and rituximab26NCT00724971R/R NHL1.8 mg/m2 once per cycle1080NoneTested in Japanese population
    Phase 1/2 combining InO and rituximab25NCT00299494Relapsed FL, relapsed DLBCL, refractory aggressive NHL1.8 mg/m2 once per cycle11887% Fl, 74% DLBCL, 20% refractory aggressive NHLNoneTested combination therapy
    Phase 224NCT00868608Refractory indolent NHL1.8 mg/m2 once per cycle8167 (31)None
    Phase 3 combining InO and rituximab vs R-chemo27NCT01232556R/R aggressive NHL1.8 mg/m2 once per cycle33841 vs 44 (R-InO vs R-chemo)3/338Compared with R-bendamustine or R-gemcitabine; stopped early for futility
    • R-, rituximab.

  • Table 2.

    Selected trials in ALL identifierDiseaseInO scheduleNo. of patientsCR, %VODNotes
    Phase 1/230NCT01363297R/R B-ALL, Ph+ included1.2-1.8 mg/m2 per cycle given on days 1, 8, 15; 1.8 for phase 272684
    Phase 228,29NCT01134575R/R B-ALL, Ph+ included1.3-1.8 mg/m2 once per cycle (n = 49). 1.8 mg/m2 per cycle given on days 1, 8, 15 (n = 41)9058 (CR + CRp + CRi)6/90, 6/36 transplant patientsNoted reduced adverse events with weekly dosing
    Phase 2 combing InO with chemotherapy41NCT01371630R/R B-ALL, Ph+ excluded1.3-1.8 mg/m2 cycle 1, 1.0-1.3 mg/m2 subsequent cycles, all dosed once per cycle5978 (CR + CRp + CRi)9/59InO combined with mini-HCVD noted to have increased VOD rate
    Phase 2 combining InO with chemotherapy42NCT01371630Newly diagnosed B-ALL, Ph+ excluded1.3-1.8 mg/m2 cycle 1, 1.0-1.3 mg/m2 subsequent cycles, all dosed once per cycle5298 (CR + CRp + CRi)4/52InO combined with mini-HCVD; first to show high response rate of InO in frontline setting
    Phase 3 INO-VATE comparing InO with chemotherapy31NCT01564784R/R B-ALL, Ph+ included1.8 mg/m2 per cycle given on days 1, 8, 15; 1.5 mg/m2 once in CR32680.7 vs 29.411% vs 1%Phase 3 trial that compared single-agent InO to chemotherapy regimens; notably increased rate of VOD
    • CRp, complete remission with incomplete platelet recovery.

  • Table 3.

    Selected ongoing trials identifierDiseaseInO schedulePatientsOpenNotes
    Phase 1/2 testing safety and efficacy of bosutinib and InONCT02311998R/R Ph+ B-ALL, CML in lymphoid blast phase1.8 mg/m2 per cycle given on days 1, 8, 15Adults 18+ yRecruitingTrial to formally evaluate MTD of TKI and InO
    Phase 3 A041501: (C10403 ± InO)NCT03150693Newly diagnosed B-ALL1.8 mg/m2 per cycle given on days 1, 8, 15Adults 18-39 yRecruitingTrial to test the addition of InO to improve frontline therapy in AYA patients
    Phase 2 hyper-CVAD + InONCT03488225Newly diagnosed B-ALL, Ph+ excluded0.6 mg/m2 day 1 and 0.3 mg/m2 day 8 of cycles 5-816 y and olderRecruitingPlan to test addition of InO to hyper-CVAD backbone
    Phase 2 testing InO for MRDNCT03441061B-ALL, Ph+ excluded, in CR with MRD+0.6 mg/m2 day 1 and 0.3 mg/m2 days 8 and 15AdultsRecruitingPlan to the tolerability and efficacy of using InO to eliminate MRD+ disease.
    Phase 2 testing low-dose InO in relapsed diseaseNCT03094611R/R B-ALL, Ph+ excludedCycle 1: 0.8 mg/m2 day 1 and 0.5 mg/m2 days 8 and 15 Subsequent cycles: 0.6 mg/m2 day 1, 0.3 mg/m2 day 8,12 y and olderRecruitingPlan to test efficacy and tolerability of a reduced dosing schedule for R/R disease
    Randomized phase 2 in DLBCL patients ineligible for anthracyclinesNCT01679119Frontline DLBCL, not anthracycline candidates0.8 mg/m2 day 2AdultRecruitingTesting replacement of anthracycline by either InO or gemcitabine to R-CHOP regimen in patients who cannot safely receive standard treatment
    • AYA, adolescent and young adult; CML, chronic myeloid leukemia; hyper-CVAD, cyclophosphamide, vincristine, doxorubicin (Adriamycin), and dexamethasone.