ライフサイエンスコーパス: ixazomib

1 a response with 4 mg and 54% with 5.5 mg of ixazomib.

2 alone, and half dose CsA (5 mg/kg per day) + ixazomib.

3 augmented autologous HSCT with melphalan and ixazomib.

4 Phase I showed feasibility of 4 mg ixazomib.

5 and 5%, respectively) received single-agent ixazomib 0.24 to 2.23 mg/m(2) (days 1, 4, 8, 11; 21-day

6 l dose cyclosporine (CsA, 10 mg/kg per day), ixazomib (0.25 mg/kg on days -5, -2 and +2) alone, and h

7 hase 1, we gave patients escalating doses of ixazomib (1.68-3.95 mg/m(2)) to establish the recommende

8 maintenance with single agent ixazomib (oral ixazomib 4 mg per day on days 1, 8, and 15 of 28-day cyc

9 azomib, thalidomide, and dexamethasone (oral ixazomib 4 mg per day on days 1, 8, and 15, oral thalido

10 d toxicity of combining 2 different doses of ixazomib (4 mg and 5.5 mg given weekly for 3 of 4 weeks)

11 ients received maintenance (lenalidomide +/- ixazomib) according to the companion PETHEMA/GEM2014MAIN

12 Compared to untreated animals, ixazomib alone or in combination with (1/2) dose CsA red

13 cycles, followed by maintenance therapy with ixazomib alone.

14 of an investigational proteasome inhibitor, ixazomib, alone and in a CNI minimization strategy in a

15 olid tumors led to the invention of MLN9708 (ixazomib), an orally bioavailable next-generation protea

16 ology is demonstrated in the synthesis of an ixazomib analogue.

17 After two cycles of ixazomib and dexamethasone, immunoglobulin M levels decr

18 ot mutant solid tumors who were treated with ixazomib and vorinostat (n = 59), those who were treated

19 Weekly oral ixazomib appears to be active in patients with relapsed/

20 inhibitors (PIs) bortezomib, carfilzomib and ixazomib are approved for the treatment of multiple myel

21 t that CNI minimization strategies including ixazomib are effective to prevent AMR including in sensi

22 imed to determine the safety and efficacy of ixazomib as maintenance therapy following ASCT.

23 week intervals, whereas in the IRD arm, oral ixazomib at a dose of 4 mg on days 1, 8, and 15 was adde

24 teasome inhibitors (bortezomib, carfilzomib, ixazomib), both in combination with rituximab, as well a

25 he less neurotoxic oral proteasome inhibitor ixazomib combined with rituximab, in patients with relap

26 evaluating the efficacy and tolerability of ixazomib-daratumumab-low-dose-dexamethasone (Ixa-Dara-de

27 heral neuropathy, and treated them with oral ixazomib (days 1, 8, 15) plus lenalidomide 25 mg (days 1

28 More importantly, ixazomib demonstrated potent anti-tumor efficacy in vivo

29 ith newly diagnosed MM receiving daratumumab-ixazomib-dexamethasone, even after adjusting for frailty

30 olled, 35 patients randomly assigned to each ixazomib dose.

31 m tolerated dose (MTD) of single-agent, oral ixazomib given weekly for 3 of 4 weeks.

32 e 4 severity occurred more frequently in the ixazomib group (12% and 7% of the patients, respectively

33 edian time to response was 1.1 months in the ixazomib group and 1.9 months in the placebo group, and

34 ence of peripheral neuropathy was 27% in the ixazomib group and 22% in the placebo group (grade 3 eve

35 similar in the two study groups (47% in the ixazomib group and 49% in the placebo group), as were th

36 108 (27%) of 394 patients in the ixazomib group and 51 (20%) of 259 patients in the place

37 he overall rates of response were 78% in the ixazomib group and 72% in the placebo group, and the cor

38 he treatment period, one patient died in the ixazomib group and none died in the placebo group.

39 Rash occurred more frequently in the ixazomib group than in the placebo group (36% vs. 23% of

40 ree survival was significantly longer in the ixazomib group than in the placebo group at a median fol

41 ve ixazomib plus lenalidomide-dexamethasone (ixazomib group) or placebo plus lenalidomide-dexamethaso

42 atio for disease progression or death in the ixazomib group, 0.74; P=0.01); a benefit with respect to

43 ted cells, the combination of venetoclax and ixazomib has unacceptable toxicity in primary cells, and

44 th creatinine clearance > 15 mL/min, whereas ixazomib in combination with lenalidomide and dexamethas

45 ss the safety, tolerability, and activity of ixazomib in combination with lenalidomide and dexamethas

46 nd Tat-B were significantly more potent than Ixazomib in inhibiting the human 20S proteasomes with IC

47 ormed the subsequent clinical development of ixazomib in multiple myeloma.

48 study illustrates the anti-tumor efficacy of ixazomib in NB both alone and in combination with dox, s

49 ficacy of the oral proteasome inhibitor (PI) ixazomib in patients with relapsed/refractory immunoglob

50 of a second-generation proteasome inhibitor, ixazomib, in T-cell lymphoma and Hodgkin lymphoma cells

51 We demonstrated that ixazomib induced potent cell death in all cell lines at

52 dose CsA, the CNI minimization strategy with ixazomib inhibited AMR and allograft injury as evidenced

53 Ixazomib inhibits dox-induced NF-kappaB activity and sen

54 dexamethasone (RD; 161 patients) vs RD plus ixazomib (IRD; 171 patients).

55 Ixazomib is an investigational, oral, proteasome inhibit

56 Ixazomib is an investigational, orally bioavailable 20S

57 Ixazomib is an oral proteasome inhibitor that is current

58 Ixazomib is an oral proteasome inhibitor which we have s

59 Ixazomib is ideally suited for maintenance therapy given

60 e, followed by maintenance with single agent ixazomib is superior to observation.

61 Ixazomib is the first investigational oral proteasome in

62 Ixazomib is the first oral proteasome inhibitor to enter

63 mined that the combination of venetoclax and ixazomib kills more latently HIV-infected cells and lead

64 single-arm I-PRISM phase II trial evaluated ixazomib, lenalidomide, and dexamethasone in 55 patients

65 daratumumab, bortezomib, and dexamethasone; ixazomib, lenalidomide, and dexamethasone; carfilzomib a

66 ment in progression-free survival (PFS) with ixazomib-lenalidomide-dexamethasone (IRd) compared with

67 mprovement in progression-free survival with ixazomib-lenalidomide-dexamethasone (ixazomib-Rd) versus

68 Ixazomib maintenance prolongs PFS and represents an addi

69 re enrolled and randomly assigned to receive ixazomib maintenance therapy (n=395) or placebo (n=261).

70 hat the proteasome inhibitors bortezomib and ixazomib markedly increased protein levels of the osteob

71 t the second generation proteasome inhibitor ixazomib (MLN9708) not only inhibits NB cell proliferati

72 ib (NCT01339871) or the proteasome inhibitor ixazomib (NCT02042989) in patients with metastatic TP53

73 (Velcade(R)), carfilzomib (Kyprolis(R)), and ixazomib (Ninlaro(R)), confirms that proteasome inhibito

74 ents were noted in phase 1: one at a dose of ixazomib of 2.97 mg/m(2) and three at 3.95 mg/m(2).

75 ere randomly assigned in a 3:2 ratio to oral ixazomib or matching placebo on days 1, 8, and 15 in 28-

76 l patients who received at least one dose of ixazomib or placebo, according to treatment actually rec

77 ), followed by maintenance with single agent ixazomib (oral ixazomib 4 mg per day on days 1, 8, and 1

78 possibilities (pomalidomide, carfilzomib and ixazomib, panobinostat, elotuzumab, and daratumumab).

79 The all-oral combination of weekly ixazomib plus lenalidomide and dexamethasone was general

80 d and refractory multiple myeloma to receive ixazomib plus lenalidomide-dexamethasone (ixazomib group

81 that a combination of investigational agents-ixazomib plus venetoclax-which reactivate latent virus a

82 f new primary malignancies were similar with ixazomib-Rd (10.3%) and placebo-Rd (11.9%).

83 Patients were randomly assigned to ixazomib-Rd (n = 360) or placebo-Rd (n = 362), stratifie

84 ysis; progression-free survival benefit with ixazomib-Rd versus placebo-Rd did not translate into a s

85 edian follow-up of 85 months, median OS with ixazomib-Rd versus placebo-Rd was 53.6 versus 51.6 month

86 Following ixazomib-Rd versus placebo-Rd, 71.7% versus 69.9% of pat

87 dicating larger magnitude of OS benefit with ixazomib-Rd versus placebo-Rd, were seen in predefined s

88 al with ixazomib-lenalidomide-dexamethasone (ixazomib-Rd) versus placebo-Rd in patients with relapsed

89 gression-free survival was observed with the ixazomib regimen, as compared with the placebo regimen,

90 onducted a multicenter phase I/II trial with ixazomib, rituximab, and dexamethasone (IRD).

91 in modification, and DNA repair processes in ixazomib-sensitive lymphoma cells.

92 Altogether, ixazomib significantly downregulates MYC and induces pot

93 genes from global transcriptome analysis for ixazomib strongly favored tumor inhibition via downregul

94 s were assigned (1:1) to consolidation using ixazomib, thalidomide, and dexamethasone (oral ixazomib

95 idation after salvage autologous HSCT, using ixazomib, thalidomide, and dexamethasone, followed by ma

96 e, the second-generation PIs carfilzomib and ixazomib, the DACI panobinostat, and 2 mAbs, elotuzumab

97 crease in second malignancies was noted with ixazomib therapy (12 [3%] patients) compared with placeb

98 The addition of ixazomib to a regimen of lenalidomide and dexamethasone

99 Furthermore, in ixazomib-treated lymphoma cells, we identified that CHK1

100 ion in the risk of progression or death with ixazomib versus placebo (median PFS 26.5 months [95% CI

101 The terminal half-life of ixazomib was 3.3 to 7.4 days; plasma exposure increased

102 Ixazomib was administered to adult patients with relapse

103 The maximum tolerated dose of ixazomib was established as 2.97 mg/m(2) and the recomme

104 Overall, the ixazomib with dexamethasone has good efficacy in relapse

105 uggesting that combination therapy including ixazomib with traditional therapeutic agents such as dox

106 20S proteasome (delanzomib, carfilzomib and ixazomib) with better pharmacologic profiles as well as