ライフサイエンスコーパス: cobimetinib

1 downstream target MEK (through trametinib or cobimetinib).

2 triplet combination versus vemurafenib plus cobimetinib.

3 rrhage) was considered to be associated with cobimetinib.

4 emurafenib and the MAPK/ERK kinase inhibitor cobimetinib.

5 inhibitor vemurafenib and the MEK inhibitor cobimetinib.

6 the concomitant addition of a MEK inhibitor, cobimetinib.

7 t combined vemurafenib with a MEK inhibitor, cobimetinib.

8 treated with atezolizumab, vemurafenib, and cobimetinib.

9 of the azetidine-containing pharmaceutical, cobimetinib.

10 e BRAF-MEK inhibitor combination vemurafenib-cobimetinib.

11 fenib 960 mg twice a day in combination with cobimetinib 60 mg 21/7.

12 hedule of vemurafenib 960 mg twice a day and cobimetinib 60 mg 28/0 had dose-limiting toxic effects-o

13 hedule of vemurafenib 960 mg twice a day and cobimetinib 60 mg once a day 21/7 had a grade 3 prolonga

14 20 mg or 960 mg twice a day continuously and cobimetinib 60 mg, 80 mg, or 100 mg once a day for eithe

15 ng an interactive response system to receive cobimetinib (60 mg once daily for 21 days followed by a

16 ib (960 mg or 720 mg twice daily orally) and cobimetinib (60 mg once daily orally; 21 days on and 7 d

17 ays 1 and 15 of each 28-day cycle) plus oral cobimetinib (60 mg once daily, days 1-21).

18 l vemurafenib (720 mg twice daily) plus oral cobimetinib (60 mg once daily, days 1-21); atezolizumab

19 ab (840 mg intravenously every 2 weeks) plus cobimetinib (60 mg orally once daily for days 1-21 of a

20 patients in cohort I were randomized 1:1 to cobimetinib (60 mg, D3-D23 of each 28-day cycle) or plac

21 Patients were randomized 1 : 1 to receive cobimetinib (60 mg, days 1-21) plus anti-programmed deat

22 en dosing regimens combining vemurafenib and cobimetinib: 66 had recently progressed on vemurafenib a

23 s (95% CI 7.00-10.61) with atezolizumab plus cobimetinib, 7.10 months (6.05-10.05) with atezolizumab,

24 hedule of vemurafenib 960 mg twice a day and cobimetinib 80 mg once a day 14/14 had grade 3 fatigue f

25 n this genotype with GDC-0973 (also known as cobimetinib), a MEK inhibitor currently in phase III cli

26 hibitor of the PI3K/mTOR pathway, along with cobimetinib, a MEK/ERK pathway inhibitor.

27 Cobimetinib added to paclitaxel did not lead to a statis

28 urvival (PFS) compared with vemurafenib plus cobimetinib alone for treatment of BRAF V600 variation m

29 cant survival benefits over vemurafenib plus cobimetinib alone, and a price reduction would be encour

30 rafenib plus cobimetinib vs vemurafenib plus cobimetinib alone.

31 Cobimetinib, an MAPK/extracellular signal-regulated kina

32 through a proof-of-concept clinical trial of cobimetinib, an oral inhibitor of MEK1 and MEK2, in pati

33 lizumab (BRAF-mutated, Cohort A, n = 15), or cobimetinib and atezolizumab (BRAF-wild-type, Cohort B,

34 on in most patients: 109 (93%) of 117 in the cobimetinib and vemurafenib group and 133 (94%) of 142 i

35 of 259 patients have died: 117 (47%) in the cobimetinib and vemurafenib group and 142 (58%) in the v

36 events occurred in 92 patients (37%) in the cobimetinib and vemurafenib group and 69 patients (28%)

37 ing at a higher frequency in patients in the cobimetinib and vemurafenib group compared with the vemu

38 utamyl transferase increase (36 [15%] in the cobimetinib and vemurafenib group vs 25 [10%] in the pla

39 ommon serious adverse events reported in the cobimetinib and vemurafenib group.

40 22.3 months (95% CI 20.3-not estimable) for cobimetinib and vemurafenib versus 17.4 months (95% CI 1

41 rvival was 12.3 months (95% CI 9.5-13.4) for cobimetinib and vemurafenib versus 7.2 months (5.6-7.5)

42 The safety profile for cobimetinib and vemurafenib was tolerable and manageable

43 We find that coinhibition of MEK (using cobimetinib) and autophagy (using mefloquine), but not e

44 either 12 weeks of neoadjuvant vemurafenib, cobimetinib, and atezolizumab (BRAF-mutated, Cohort A, n

45 iving different MEK inhibitors (selumetinib, cobimetinib, and trametinib) developed an eruption, all

46 with the doublet regimen of vemurafenib plus cobimetinib, at an ICER of $271 669 per QALY, which is n

47 day cycles of atezolizumab, vemurafenib, and cobimetinib (atezolizumab group) or atezolizumab placebo

48 al (PFS) with atezolizumab, vemurafenib, and cobimetinib (atezolizumab group) versus placebo, vemuraf

49 th first-line atezolizumab, vemurafenib, and cobimetinib (atezolizumab group) versus placebo, vemuraf

50 tients with RDD who underwent treatment with cobimetinib between January 1, 2013, and December 1, 202

51 inatorial therapy involving bromosporine and cobimetinib (bromo/cobi) showed synergistic anti-tumor e

52 positive melanoma to receive vemurafenib and cobimetinib (combination group) or vemurafenib and place

53 These data confirm the clinical benefit of cobimetinib combined with vemurafenib and support the us

54 improved with atezolizumab, vemurafenib, and cobimetinib compared with placebo, vemurafenib, and cobi

55 umab group) versus placebo, vemurafenib, and cobimetinib (control group) in patients with BRAF(V600)

56 umab group) versus placebo, vemurafenib, and cobimetinib (control group) in patients with BRAF(V600)-

57 p) or atezolizumab placebo, vemurafenib, and cobimetinib (control group).

58 atezolizumab combined with vemurafenib plus cobimetinib could be cost-effective at 20-year (ICER, $1

59 n of 7 in combination with the MEK inhibitor cobimetinib demonstrated synergistic pathway inhibition

60 pictilisib (GDC-0941) and the MEK inhibitor cobimetinib (GDC-0973) suppresses cell proliferation and

61 1%) of 179 patients in the atezolizumab plus cobimetinib group, 28 (31%) of 90 in the atezolizumab gr

62 olled (183 patients in the atezolizumab plus cobimetinib group, 90 in the atezolizumab group, and 90

63 e BRAF-MEK inhibitor combination vemurafenib-cobimetinib in 28-day cycles.

64 udy was designed to assess atezolizumab plus cobimetinib in metastatic colorectal cancer.

65 ion with vemurafenib and MEK inhibition with cobimetinib in patients with advanced BRAF-mutated melan

66 inib compared with placebo, vemurafenib, and cobimetinib in patients with BRAF(V600) mutation-positiv

67 ination with cobimetinib or vemurafenib plus cobimetinib in patients with melanoma with CNS metastase

68 received atezolizumab plus vemurafenib plus cobimetinib in the BRAF(V600) mutation-positive cohort,

69 received atezolizumab plus vemurafenib plus cobimetinib in the BRAF(V600) mutation-positive cohort,

70 f 15 patients treated with atezolizumab plus cobimetinib in the BRAF(V600) wild-type cohort had treat

71 free survival (PFS), adverse events (AEs) of cobimetinib in the entire cohort, and ORRs and PFS based

72 total of 16 patients (median [range] age at cobimetinib initiation, 57 [31-74] years; 11 [69%] women

73 Triple therapy (cobimetinib + mefloquine + aCD40) achieved cytotoxic T-c

74 PD-L1) as monotherapy or in combination with cobimetinib (MEK inhibitor).

75 cle 1, all patients received vemurafenib and cobimetinib only; atezolizumab placebo was added from cy

76 e report the comparison of atezolizumab plus cobimetinib or atezolizumab monotherapy versus regorafen

77 oved overall survival with atezolizumab plus cobimetinib or atezolizumab versus regorafenib.

78 to evaluate atezolizumab in combination with cobimetinib or vemurafenib plus cobimetinib in patients

79 rafenib plus cobimetinib), RAS/NF (cohort 2, cobimetinib), or non-BRAF/RAS/NF (cohort 3, bevacizumab)

80 rt I, ORR was 38.3% (95% CI 24.40-52.20) for cobimetinib/paclitaxel and 20.9% (95% CI 8.77-33.09) for

81 ansion stages, median PFS was 5.5 months for cobimetinib/paclitaxel versus 3.8 months for placebo/pac

82 domized (1:1) to cohort II or III to receive cobimetinib plus atezolizumab (840 mg, D1 and D15) and e

83 tated BRAF V600E tumors received vemurafenib/cobimetinib plus atezolizumab (cohort 1); those with mut

84 RAS, KRAS, or HRAS) or NF1/2 tumors received cobimetinib plus atezolizumab (cohort 2).

85 019, 446 patients were randomized to receive cobimetinib plus atezolizumab (n = 222) or pembrolizumab

86 rious AEs occurred in 44.1% of patients with cobimetinib plus atezolizumab and 20.8% with pembrolizum

87 nths [interquartile range (IQR) 4.8-9.9] for cobimetinib plus atezolizumab and 7.2 months (IQR 4.9-10

88 Cobimetinib plus atezolizumab and a taxane did not appea

89 Cobimetinib plus atezolizumab did not improve PFS compar

90 sed blood creatine phosphokinase (10.0% with cobimetinib plus atezolizumab versus 0.9% with pembroliz

91 [95% confidence interval (CI) 3.8-7.2] with cobimetinib plus atezolizumab versus 5.7 months (95% CI

92 -cohort phase II study evaluating first-line cobimetinib plus chemotherapy, with or without atezolizu

93 s were enrolled and randomly assigned to the cobimetinib plus vemurafenib group (n=247) or placebo pl

94 Adding atezolizumab to vemurafenib and cobimetinib provided an additional 3.267 QALYs compared

95 Atezolizumab plus vemurafenib and cobimetinib provided intracranial activity in patients w

96 Adding atezolizumab to vemurafenib plus cobimetinib provided promising intracranial activity in

97 llow: BRAF V600E (cohort 1, vemurafenib plus cobimetinib), RAS/NF (cohort 2, cobimetinib), or non-BRA

98 t that the atezolizumab and vemurafenib plus cobimetinib regimen provides significant survival benefi

99 nib, encorafenib/binimetinib, or vemurafenib/cobimetinib should be offered in BRAF-mutant disease.

100 tment with atezolizumab and vemurafenib plus cobimetinib significantly improved progression-free surv

101 The addition of cobimetinib to vemurafenib was associated with a signifi

102 Cobimetinib treatment was efficacious regardless of geno

103 Exploratory biomarker data show that the cobimetinib + vemurafenib run-in was associated with an

104 iple combination therapy with atezolizumab + cobimetinib + vemurafenib, after a 28-d run-in period wi

105 vemurafenib, after a 28-d run-in period with cobimetinib + vemurafenib, had substantial but manageabl

106 nation of atezolizumab with vemurafenib plus cobimetinib vs vemurafenib plus cobimetinib alone.

107 Cobimetinib was administered at a dosage of 20 to 60 mg

108 Vemurafenib and cobimetinib was associated with a nonsignificantly highe

109 In this cohort study, treatment with cobimetinib was associated with positive outcomes in KRA

110 The safety of atezolizumab plus cobimetinib was consistent with those of the individual

111 Recently, the MEK1/2 inhibitor cobimetinib was FDA-approved for patients with adult his

112 mab to targeted therapy with vemurafenib and cobimetinib was safe and tolerable and significantly inc

113 The combination of vemurafenib and cobimetinib was safe and tolerable when administered at

114 All patients treated with vemurafenib and cobimetinib were included in safety and efficacy analyse

115 The combination of cobimetinib with vemurafenib improves progression-free s