ライフサイエンスコーパス: daratumumab

1 and ixazomib, panobinostat, elotuzumab, and daratumumab).

2 eactivity, and specificity of [(89)Zr]Zr-DFO-daratumumab.

3 achieved with a 200-fold excess of unlabeled daratumumab.

4 to target one another after the addition of daratumumab.

5 CD38, the target of the therapeutic antibody daratumumab.

6 Patients received daratumumab 16 mg/kg at the recommended dosing schedule,

7 e reported for the 106 patients who received daratumumab 16 mg/kg in parts 1 and 2.

8 In this pooled data set, daratumumab 16 mg/kg monotherapy demonstrated rapid, dee

9 pooled analysis of 148 patients treated with daratumumab 16 mg/kg.

10 alone (control group) or in combination with daratumumab (16 mg per kilogram of body weight) (daratum

11 ocated in a 1:1 ratio to receive intravenous daratumumab 8 mg/kg or 16 mg/kg in part 1 stage 1 of the

12 previously treated AL patients who received daratumumab, a CD38-directed monoclonal antibody approve

13 We studied daratumumab, a CD38-targeting, human IgG1kappa monoclona

14 Daratumumab, a human CD38 immunoglobulin G1 kappa (IgG1k

15 Daratumumab, a human IgGkappa monoclonal antibody that t

16 We assessed daratumumab, a novel CD38-targeted monoclonal antibody,

17 e, 30 patients received 8 mg per kilogram of daratumumab and 42 received 16 mg per kilogram, administ

18 possible additional mechanisms of action for daratumumab and deserves further exploration.

19 ave shown enhanced therapeutic efficacy when daratumumab and isatuximab are combined with other agent

20 ill review data on the use of elotuzumab and daratumumab and provide a foundation for their use in cu

21 Furthermore, daratumumab, and probably also other CD38-targeting anti

22 , the dose-escalation phase, we administered daratumumab at doses of 0.005 to 24 mg per kilogram of b

23 Part 2 (dose expansion) evaluated daratumumab at the recommended phase 2 dose (RP2D) plus

24 based on lenalidomide/bortezomib resistance, daratumumab availability, and cost.

25 s, daratumumab is clearly a breakthrough and daratumumab-based combinations might become the preferre

26 Daratumumab binds a unique CD38 epitope and showed stron

27 Daratumumab bioconjugates are being evaluated for image-

28 Confocal microscopy with daratumumab-Cy5 demonstrated specific cell binding.

29 In this study, we show that daratumumab (DARA), a therapeutic human CD38 mAb with a

30 [(89)Zr]Zr-DFO- and Cy5-daratumumab demonstrated superb binding to CD38(+) human

31 g) was reproducibly obtained with [(89)Zr]Zr-daratumumab-DFO.

32 levels on MM cells increased again following daratumumab discontinuation.

33 Part 1 (dose escalation) evaluated 4 daratumumab doses plus lenalidomide (25 mg/day orally on

34 lopment of several CD38 antibodies including daratumumab (fully human), isatuximab (chimeric), and MO

35 grade 3 or 4 adverse events reported in the daratumumab group and the control group were thrombocyto

36 ression-free survival was not reached in the daratumumab group and was 7.2 months in the control grou

37 e rate of overall response was higher in the daratumumab group than in the control group (82.9% vs. 6

38 ree survival was significantly higher in the daratumumab group than in the control group; the 12-mont

39 f progression-free survival was 60.7% in the daratumumab group versus 26.9% in the control group.

40 tumumab (16 mg per kilogram of body weight) (daratumumab group).

41 ere reported in 45.3% of the patients in the daratumumab group; these reactions were mostly grade 1 o

42 Daratumumab has single agent activity and a limited toxi

43 myeloma, and trials for both elotuzumab and daratumumab have demonstrated significant activity when

44 ACI panobinostat, and 2 mAbs, elotuzumab and daratumumab, have been approved, incorporated into clini

45 or relapsed and refractory multiple myeloma, daratumumab in combination with bortezomib and dexametha

46 ts Single-agent activity was seen when using daratumumab in refractory myeloma, and trials for both e

47 In parallel, daratumumab induced robust increases in helper and cytot

48 In PB and BM, daratumumab induced significant increases in CD8(+):CD4(

49 nd circulating MM cells, following the first daratumumab infusion.

50 acokinetics, immunogenicity, and accelerated daratumumab infusions were studied.

51 uration on reagent red blood cells mitigates daratumumab interference with transfusion laboratory ser

52 Daratumumab is a highly effective agent that produced ra

53 Daratumumab is a U.S. Food and Drug Administration-appro

54 Among these agents, daratumumab is clearly a breakthrough and daratumumab-ba

55 The anti-CD38 monoclonal antibody daratumumab is well tolerated and has high single agent

56 rious therapeutic CD38 antibodies, including daratumumab, isatuximab, and MOR202.

57 e basis of this analysis, the combination of daratumumab, lenalidomide, and dexamethasone seems to be

58 Results The combination of daratumumab, lenalidomide, and dexamethasone was identif

59 This resulted in significant enhancement of daratumumab-mediated complement-dependent cytotoxicity.

60 showed that IFNgamma significantly increased daratumumab-mediated cytotoxicity, as measured both by (

61 her, these studies show a novel mechanism of daratumumab-mediated killing and a possible new therapeu

62 In a cohort of 102 patients treated with daratumumab monotherapy (16 mg/kg), we found that pretre

63 Daratumumab monotherapy had a favorable safety profile a

64 The efficacy and favorable safety profile of daratumumab monotherapy in multiple myeloma (MM) was pre

65 Daratumumab monotherapy showed encouraging efficacy in h

66 ents with relapsed/refractory myeloma from 2 daratumumab monotherapy studies were analyzed before and

67 observed with lenalidomide/dexamethasone or daratumumab monotherapy.

68 ts eventually develop progressive disease to daratumumab monotherapy.

69 e evaluated [(89)Zr]Zr-desferrioxamine (DFO)-daratumumab PET/CT imaging in MM tumor models.

70 [(89)Zr]Zr-DFO-daratumumab PET/CT small-animal imaging was performed in

71 [(89)Zr]Zr-DFO-daratumumab/PET demonstrated specificity and sensitivity

72 were efficiently imaged with [(89)Zr]Zr-DFO-daratumumab/PET.

73 This phase 1/2 study investigated daratumumab plus lenalidomide/dexamethasone in refractor

74 Daratumumab plus lenalidomide/dexamethasone resulted in

75 increased neutropenia, the safety profile of daratumumab plus pom-dex was consistent with that of the

76 The safety profile of daratumumab plus pom-dex was similar to that of pom-dex

77 Daratumumab plus pomalidomide and dexamethasone (pom-dex

78 sion on MM cells from patients who developed daratumumab resistance, to approximately pretreatment va

79 t express CD38, which prompted evaluation of daratumumab's effects on CD38-positive immune subpopulat

80 t role for CD38 and CIP expression levels in daratumumab sensitivity and suggest that therapeutic com

81 evaluated for immunosuppressive activity and daratumumab sensitivity in the myeloma setting.

82 t 7 d after administration of [(89)Zr]Zr-DFO-daratumumab showed prominent tumor uptake (27.7 +/- 7.6

83 , we found that treatment with IFNgamma plus daratumumab significantly attenuated tumor growth.

84 that of pom-dex alone, with the exception of daratumumab-specific infusion-related reactions (50%) an

85 Daratumumab targets CD38-expressing myeloma cells throug

86 than CD38-negative Tregs and were reduced in daratumumab-treated patients.

87 -related reactions that were associated with daratumumab treatment were reported in 45.3% of the pati

88 (hazard ratio for progression or death with daratumumab vs. control, 0.39; 95% confidence interval,

89 The overall hematologic response rate to daratumumab was 76%, including CR in 36% and very good p

90 Daratumumab was administered at 16 mg/kg weekly for 8 we

91 Daratumumab was conjugated to Cyanine5 (Cy5) dye for cel

92 Daratumumab was conjugated to DFO-p-benzyl-isothiocyanat

93 tro and in vivo evaluation of [(89)Zr]Zr-DFO-daratumumab was performed using CD38(+) human myeloma MM

94 Daratumumab was well tolerated; fatigue (42 [40%] patien

95 l patients who received at least one dose of daratumumab were included in the analysis.