ライフサイエンスコーパス: idelalisib

1 of mature B-cell lymphoma (e.g., ibrutinib, idelalisib).

2 R-1202 in aggressive lymphoma not found with idelalisib.

3 Administration-approved p110delta inhibitor idelalisib.

4 killing by the PI3K-delta-specific inhibitor idelalisib.

5 phenotype taken on by CLL cells treated with idelalisib.

6 fficiently by sunitinib than by ibrutinib or idelalisib.

7 available small molecule PI3Kdelta inhibitor idelalisib.

8 s that confer the potency and selectivity of idelalisib.

9 ocked by ibrutinib and fostamatinib, but not idelalisib.

10 ity of inhibiting the PI3Kdelta pathway with idelalisib.

11 Eligible subjects received idelalisib (100 mg twice daily) or placebo for 7 days, w

12 de 10 mg on days 1-21 every 28 days and oral idelalisib 150 mg twice a day with continuous 28-day cyc

13 e 15 mg on days 1-21 in a 28 day cycle, oral idelalisib 150 mg twice a day with continuous 28-day cyc

14 ted with rituximab 375 mg/m(2) weekly x8 and idelalisib 150 mg twice daily continuously for 48 weeks.

15 eive either idelalisib plus ofatumumab (oral idelalisib 150 mg twice daily continuously plus ofatumum

16 2-6) in addition to either twice-daily oral idelalisib (150 mg) or placebo until disease progression

17 receipt of those therapies were administered idelalisib, 150 mg twice daily, until the disease progre

18 s on 178 patients with CLL (ibrutinib = 143; idelalisib = 35) who discontinued KI therapy.

19 e assessed the efficacy and safety of adding idelalisib, a first-in-class targeted phosphoinositide-3

20 ased on CLL cells from patients treated with idelalisib, a phosphoinositide-3-kinase delta inhibitor

21 Idelalisib, a selective inhibitor of PI3Kdelta, is appro

22 ho had not received previous lenalidomide or idelalisib (A051201) were started with oral lenalidomide

23 into the blood through distinct mechanisms: idelalisib actively promotes egress by upregulating S1PR

24 Idelalisib (also known as GS-1101, CAL-101, IC489666, an

25 more, the PI3K p110delta-specific inhibitor, idelalisib, also demonstrates activity against primary l

26 Idelalisib, an oral inhibitor of phosphatidylinositol-3-

27 tudy, we assessed the efficacy and safety of idelalisib, an oral inhibitor of the delta isoform of ph

28 In a phase 1 study, idelalisib, an orally active selective PI3Kdelta inhibit

29 he safety and efficacy of the combination of idelalisib and entospletinib.

30 lity of the BCR-associated kinase inhibitors idelalisib and ibrutinib, approved for treatment of CLL

31 he past year with the regulatory approval of idelalisib and ibrutinib, with other therapeutic small m

32 ts occurred in 40% of the patients receiving idelalisib and rituximab and in 35% of those receiving p

33 The combination of idelalisib and rituximab was highly active, resulting in

34 The combination of idelalisib and rituximab, as compared with placebo and r

35 owed by 6 months of combination therapy with idelalisib and the anti-CD20 antibody ofatumumab.

36 In this work, we show that ibrutinib, idelalisib, and dasatinib, drugs that block B cell recep

37 naling pathway inhibitors such as ibrutinib, idelalisib, and fostamatinib (respective inhibitors of B

38 To evaluate idelalisib as front-line therapy, we enrolled 24 subject

39 To evaluate idelalisib as initial therapy, 64 treatment-naive older

40 e results support the further development of idelalisib as initial treatment of CLL.

41 short hairpin RNA complements the effects of idelalisib, as a single agent or in combination with car

42 ng illnesses to receive rituximab and either idelalisib (at a dose of 150 mg) or placebo twice daily.

43 n diseases, we needed a clear picture of how idelalisib binds to and inhibits PI3Kdelta.

44 se inhibitor ibrutinib or the PI3K inhibitor idelalisib block B-cell receptor induced activation of L

45 A crystal structure of idelalisib bound to the p110delta subunit of PI3Kdelta f

46 mphoma cell lines, and patients treated with idelalisib, but not ibrutinib, showed increased somatic

47 reatment with a specific PI3Kdelta inhibitor Idelalisib (CAL-101) suppresses E2F1 and c-Myc levels an

48 gs for leukaemia or lymphoma therapy such as idelalisib, duvelisib and ibrutinib block PI3Kdelta acti

49 shown that an oral PI3K p110delta inhibitor idelalisib exhibits promising activity in CLL.

50 approval of one isoform-selective inhibitor (idelalisib) for treatment of certain blood cancers and a

51 umonia, and pyrexia, were more common in the idelalisib group (140 [68%] of 207 patients) than in the

52 the placebo group and was not reached in the idelalisib group (hazard ratio for progression or death

53 al was 20.8 months (95% CI 16.6-26.4) in the idelalisib group and 11.1 months (8.9-11.1) in the place

54 o death occurred in 23 (11%) patients in the idelalisib group and 15 (7%) in the placebo group, inclu

55 including six deaths from infections in the idelalisib group and three from infections in the placeb

56 reased risk of infection was reported in the idelalisib group compared with the placebo group (grade

57 quent grade 3 or worse adverse events in the idelalisib group were neutropenia (124 [60%] of 207 pati

58 hazard ratio for progression or death in the idelalisib group, 0.15; P<0.001).

59 In a phase 1 trial, idelalisib (GS-1101, CAL-101), a selective inhibitor of

60 Idelalisib (GS-1101, CAL-101), an oral inhibitor of phos

61 The PI3Kdelta inhibitor, idelalisib, has been most widely studied in lymphoma, an

62 e currently applied inhibitors ibrutinib and idelalisib have limited capacity however to induce cell

63 mber of single agents, such as ibrutinib and idelalisib, have demonstrated impressive efficacy with a

64 esistance, both proven and hypothesized, for idelalisib, ibrutinib, and venetoclax, describe patterns

65 activation can be inhibited by ibrutinib or idelalisib.IMPORTANCE EBV establishes viral latency in B

66 e aimed to assess the efficacy and safety of idelalisib in combination with a second-generation anti-

67 INTERPRETATION: Idelalisib in combination with bendamustine plus rituxim

68 ibitor ibrutinib and the PI3Kdelta inhibitor idelalisib in more than half of the cases had only a par

69 findings support the further development of idelalisib in patients with CLL.

70 nalidomide in combination with rituximab and idelalisib in relapsed follicular and mantle cell lympho

71 e to selective PI3Kdelta inhibitor, CAL-101 (idelalisib), in mouse xenograft models.

72 linking, whereas treatment of CLL cells with idelalisib increased S1PR1 expression and migration towa

73 Idelalisib induced disease regression in 46/54 (85%) of

74 ritical to B-cell development (with CAL-101 [idelalisib]), interrupts a double-negative feedback loop

75 Idelalisib is a first-in-class oral inhibitor of PI3Kdel

76 Our data show that idelalisib is a potent and selective inhibitor of the ki

77 Idelalisib is a small-molecule inhibitor of PI3Kdelta wi

78 Idelalisib is an oral phosphatidylinositol 3-kinase delt

79 Idelalisib is well tolerated and active in heavily pretr

80 INTERPRETATION: The combination of idelalisib, lenalidomide, and rituximab in these trials

81 Idelalisib-mediated inhibition of PI3Kdelta led to abrog

82 in a phase 2 study consisting of 2 months of idelalisib monotherapy followed by 6 months of combinati

83 eived idelalisib/placebo (n = 21) or placebo/idelalisib (n = 20).

84 s were enrolled and randomly assigned to the idelalisib (n=207) and placebo (n=209) groups.

85 ct of the PI3K p110delta-selective inhibitor idelalisib on allergic responses.

86 ithout progression could continue to receive idelalisib on an extension study.

87 that treatment of primary mouse B cells with idelalisib or duvelisib, and to a lesser extent ibrutini

88 compared with placebo (treatment difference [idelalisib - placebo], -1.78; 95% CI, -2.53 to -1.03; P

89 one patients with allergic rhinitis received idelalisib/placebo (n = 21) or placebo/idelalisib (n = 2

90 ode, and assigned patients to receive either idelalisib plus ofatumumab (oral idelalisib 150 mg twice

91 INTERPRETATION: The idelalisib plus ofatumumab combination resulted in bette

92 22 treatment-related deaths occurred in the idelalisib plus ofatumumab group (the most common being

93 al was 16.3 months (95% CI 13.6-17.8) in the idelalisib plus ofatumumab group and 8.0 months (5.7-8.2

94 Serious infections were more common in the idelalisib plus ofatumumab group and included pneumonia

95 included pneumonia (23 [13%] patients in the idelalisib plus ofatumumab group vs nine [10%] in the of

96 quent grade 3 or worse adverse events in the idelalisib plus ofatumumab group were neutropenia (59 [3

97 hrombocytopenia (six [7%] vs 19 [11%] in the idelalisib plus ofatumumab group).

98 tients were treated at 6 dose levels of oral idelalisib (range 50-350 mg once or twice daily) and rem

99 In this single-group study, idelalisib showed antitumor activity with an acceptable

100 th grass pollen) was substantially lower for idelalisib-treated compared with placebo-treated subject

101 ymptom scores were lower during the combined idelalisib treatment periods compared with placebo (trea

102 Idelalisib treatment resulted in nodal responses in 81%

103 Median duration of idelalisib treatment was 3.5 months (range, 0.7-30.7), w

104 Idelalisib treatment was well tolerated in patients with

105 Idelalisib treatment was well tolerated.

106 ma CCL17 and CCL22 levels were reduced after idelalisib treatment.

107 ed from patients with acquired resistance to idelalisib treatment.

108 Patients receiving idelalisib versus those receiving placebo had improved r

109 were lower in patients taking steroids when idelalisib was reinitiated.

110 dose regimens of idelalisib were evaluated; idelalisib was taken once or twice daily continuously at

111 02, but not the approved PI3Kdelta inhibitor idelalisib, was highly synergistic with the proteasome i

112 Eight dose regimens of idelalisib were evaluated; idelalisib was taken once or

113 es were safety and tolerability of combining idelalisib with lenalidomide and rituximab in patients w