ライフサイエンスコーパス: ipilimumab

1 ollowed by a standard course of anti-CTLA-4 (ipilimumab).

2 e progression while receiving treatment with ipilimumab.

3 ed to T-VEC, and 21.1% had AEs attributed to ipilimumab.

4 nd early intervention for patients receiving ipilimumab.

5 mbrolizumab in combination with reduced-dose ipilimumab.

6 ompared with those that block CTLA-4 such as ipilimumab.

7 fficacy of androgen deprivation therapy plus ipilimumab.

8 before (i.e., baseline) and up to 4 wk after ipilimumab.

9 PD-L1, and previous best overall response to ipilimumab.

10 mmune-related adverse events associated with ipilimumab.

11 ty without additional safety concerns versus ipilimumab.

12 for death with nivolumab plus ipilimumab vs. ipilimumab, 0.55 [P<0.001]; hazard ratio for death with

13 ]; hazard ratio for death with nivolumab vs. ipilimumab, 0.65 [P<0.001]).

14 received intravenous nivolumab 3 mg/kg plus ipilimumab 1 mg/kg (N3I1), nivolumab 1 mg/kg plus ipilim

15 No patients in the nivolumab 1 mg/kg plus ipilimumab 1 mg/kg cohort had a grade 3 or 4 treatment-r

16 and ten (19%) in the nivolumab 3 mg/kg plus ipilimumab 1 mg/kg cohort; the most commonly reported gr

17 patient who received nivolumab 3 mg/kg plus ipilimumab 1 mg/kg died from treatment-related pneumonit

18 weeks, nivolumab 3 mg/kg every 2 weeks plus ipilimumab 1 mg/kg every 12 weeks, or nivolumab 3 mg/kg

19 enous pembrolizumab 2 mg/kg plus intravenous ipilimumab 1 mg/kg every 3 weeks for four doses, followe

20 eks, or nivolumab 3 mg/kg every 2 weeks plus ipilimumab 1 mg/kg every 6 weeks until disease progressi

21 receive nivolumab 1 mg/kg every 2 weeks plus ipilimumab 1 mg/kg every 6 weeks, nivolumab 3 mg/kg ever

22 and four (7%) in the nivolumab 3 mg/kg plus ipilimumab 1 mg/kg group discontinued treatment due to t

23 3 mg/kg, and 54 with nivolumab 3 mg/kg plus ipilimumab 1 mg/kg).

24 ee patients receiving nivolumab 1 mg/kg plus ipilimumab 1 mg/kg, 14 (23%) of 61 receiving nivolumab 1

25 R not calculable) for nivolumab 1 mg/kg plus ipilimumab 1 mg/kg, 361.0 days (273.0-470.0) for nivolum

26 b 3 mg/kg, three with nivolumab 1 mg/kg plus ipilimumab 1 mg/kg, 61 with nivolumab 1 mg/kg plus ipili

27 (19%) of 54 receiving nivolumab 3 mg/kg plus ipilimumab 1 mg/kg.

28 ipilimumab 3 mg/kg or nivolumab 3 mg/kg plus ipilimumab 1 mg/kg.

29 bination beginning at nivolumab 1 mg/kg plus ipilimumab 1 mg/kg.

30 ays (248.0-288.0) for nivolumab 3 mg/kg plus ipilimumab 1 mg/kg.

31 or unacceptable toxicity), or nivolumab plus ipilimumab (1 mg/kg plus 1 mg/kg, 1 mg/kg plus 3 mg/kg,

32 ients were enrolled and randomly assigned to ipilimumab 10 mg/kg (365 patients; 364 treated) or ipili

33 vival was 15.7 months (95% CI 11.6-17.8) for ipilimumab 10 mg/kg compared with 11.5 months (9.9-13.3)

34 atment-related grade 3-4 adverse events with ipilimumab 10 mg/kg compared with ipilimumab 3 mg/kg in

35 ow-up was 14.5 months (IQR 4.6-42.3) for the ipilimumab 10 mg/kg group and 11.2 months (4.9-29.4) for

36 permuted block method using block size 4 to ipilimumab 10 mg/kg or 3 mg/kg, administered by intraven

37 ive voice response system, to receive either ipilimumab 10 mg/kg or placebo every 3 weeks for four do

38 al, patients were randomly assigned (2:1) to ipilimumab 10 mg/kg or placebo every 3 weeks for up to f

39 Ipilimumab 10 mg/kg or placebo maintenance therapy was a

40 ETATION: In patients with advanced melanoma, ipilimumab 10 mg/kg resulted in significantly longer ove

41 trial comparing the benefit-risk profile of ipilimumab 10 mg/kg versus 3 mg/kg.

42 10(6) cells administered intravenously) plus ipilimumab (10 mg/kg every 3 weeks for a total of four a

43 Of the 30 patients who received ipilimumab (17 [57%] male; median [range] age, 59.5 [30-

44 prostate-specific antigen response rate with ipilimumab (23%) than with placebo (8%).

45 umab 10 mg/kg (365 patients; 364 treated) or ipilimumab 3 mg/kg (362 patients; all treated).

46 /kg compared with 11.5 months (9.9-13.3) for ipilimumab 3 mg/kg (hazard ratio 0.84, 95% CI 0.70-0.99;

47 604), and the majority of patients received ipilimumab 3 mg/kg (n = 965) or 10 mg/kg (n = 706).

48 mumab 1 mg/kg (N3I1), nivolumab 1 mg/kg plus ipilimumab 3 mg/kg (N1I3), or nivolumab 3 mg/kg plus ipi

49 ab 3 mg/kg (N1I3), or nivolumab 3 mg/kg plus ipilimumab 3 mg/kg (N3I3) every 3 weeks for four doses f

50 hort, 18 (30%) in the nivolumab 1 mg/kg plus ipilimumab 3 mg/kg cohort, and ten (19%) in the nivoluma

51 patients who received nivolumab 1 mg/kg plus ipilimumab 3 mg/kg died from treatment-related adverse e

52 followed by a planned switch to intravenous ipilimumab 3 mg/kg every 3 weeks for four doses, or the

53 at least one dose of nivolumab 1 mg/kg plus ipilimumab 3 mg/kg every 3 weeks x 4 and then nivolumab

54 p, seven (11%) in the nivolumab 1 mg/kg plus ipilimumab 3 mg/kg group, and four (7%) in the nivolumab

55 /kg group and 11.2 months (4.9-29.4) for the ipilimumab 3 mg/kg group.

56 vents with ipilimumab 10 mg/kg compared with ipilimumab 3 mg/kg in patients with advanced melanoma.

57 In 120 patients treated prospectively with ipilimumab 3 mg/kg infused over 30 minutes, seven patien

58 travenous infusion of nivolumab 1 mg/kg plus ipilimumab 3 mg/kg or ipilimumab 3 mg/kg plus placebo, e

59 were then assigned to nivolumab 1 mg/kg plus ipilimumab 3 mg/kg or nivolumab 3 mg/kg plus ipilimumab

60 nivolumab 1 mg/kg plus ipilimumab 3 mg/kg or ipilimumab 3 mg/kg plus placebo, every 3 weeks for four

61 ays (273.0-470.0) for nivolumab 1 mg/kg plus ipilimumab 3 mg/kg, and 260.5 days (248.0-288.0) for niv

62 umab 1 mg/kg, 61 with nivolumab 1 mg/kg plus ipilimumab 3 mg/kg, and 54 with nivolumab 3 mg/kg plus i

63 (23%) of 61 receiving nivolumab 1 mg/kg plus ipilimumab 3 mg/kg, and ten (19%) of 54 receiving nivolu

64 gnificantly longer overall survival than did ipilimumab 3 mg/kg, but with increased treatment-related

65 patients who received nivolumab 1 mg/kg plus ipilimumab 3 mg/kg, every 3 weeks for four doses, follow

66 assigned patients in a 2:1 ratio to receive ipilimumab (3 mg per kilogram of body weight) combined w

67 Ipilimumab (3 mg/kg every 3 weeks; up to four doses) beg

68 Ipilimumab (3 mg/kg) was administered intravenously ever

69 heckpoint inhibitors nivolumab, 1 mg/kg, and ipilimumab, 3 mg/kg.

70 heckpoint inhibitor), alone or combined with ipilimumab (a cytotoxic T-lymphocyte antigen-4 checkpoin

71 VEC; an oncolytic virus) in combination with ipilimumab (a cytotoxic T-lymphocyte-associated antigen

72 Treatment with ipilimumab, a fully human CTLA-4-specific mAb, showed du

73 Immunologic checkpoint blockade with ipilimumab, a monoclonal antibody that blocks cytotoxic

74 most patients during the induction phase of ipilimumab administration, overall HRQoL, as measured by

75 d with four (9%) of 46 patients who received ipilimumab alone (including diarrhoea in two [4%] of 46

76 e laherparepvec plus ipilimumab (n = 98), or ipilimumab alone (n = 100).

77 weeks; up to four doses) began week 1 in the ipilimumab alone arm and week 6 in the combination arm.

78 patients) and hypophysitis (two [4%]) in the ipilimumab alone group.

79 al and a higher objective response rate than ipilimumab alone in a phase 3 trial involving patients w

80 imogene laherparepvec plus ipilimumab versus ipilimumab alone in patients with advanced melanoma in a

81 o improved outcomes compared with first-line ipilimumab alone in patients with advanced melanoma.

82 nivolumab plus ipilimumab was compared with ipilimumab alone in patients with metastatic melanoma.

83 able toxicity, whereas patients allocated to ipilimumab alone received placebo every 2 weeks during t

84 mumab alone, 42%), chills (combination, 53%; ipilimumab alone, 3%), and diarrhea (combination, 42%; i

85 alone, 3%), and diarrhea (combination, 42%; ipilimumab alone, 35%).

86 ts (AEs) included fatigue (combination, 59%; ipilimumab alone, 42%), chills (combination, 53%; ipilim

87 on-free survival compared with standard-dose ipilimumab alone, but increases toxicity.

88 ipilimumab or with nivolumab alone than with ipilimumab alone.

89 ients to nivolumab plus ipilimumab and 47 to ipilimumab alone.

90 with nine (20%) of 46 patients who received ipilimumab alone.

91 umab (an anti-CTLA-4 antibody) compared with ipilimumab alone.

92 volumab alone, nivolumab plus ipilimumab, or ipilimumab alone.

93 cantly longer progression-free survival than ipilimumab alone.

94 imogene laherparepvec plus ipilimumab versus ipilimumab alone.

95 talimogene laherparepvec plus ipilimumab or ipilimumab alone.

96 .6% (95% CI 38.1-66.8) for those assigned to ipilimumab alone; median overall survival had not been r

97 on of nivolumab (an anti-PD-1 antibody) plus ipilimumab (an anti-CTLA-4 antibody) compared with ipili

98 Ipilimumab, an immunoglobulin G1 monoclonal antibody dir

99 ab and 202 to placebo; 399 were treated with ipilimumab and 199 with placebo.

100 r hundred patients were randomly assigned to ipilimumab and 202 to placebo; 399 were treated with ipi

101 omly assigning 95 patients to nivolumab plus ipilimumab and 47 to ipilimumab alone.

102 3-72.6) for those assigned to nivolumab plus ipilimumab and 53.6% (95% CI 38.1-66.8) for those assign

103 ple of prostate cancer subjects treated with Ipilimumab and granulocyte macrophage colony stimulating

104 anoma who developed fatal myocarditis during ipilimumab and nivolumab combination immunotherapy; thes

105 7% of patients treated with a combination of ipilimumab and nivolumab, which suggests that our patien

106 He began systemic therapy with ipilimumab and nivolumab.

107 l myocarditis developed after treatment with ipilimumab and nivolumab.

108 t-related AEs was higher with nivolumab plus ipilimumab and occurred earlier than historical experien

109 Ipilimumab and other immune therapies are effective trea

110 ndicating that direct steric overlap between ipilimumab and the B7 ligands is a major mechanistic con

111 Patients with melanoma that progresses on ipilimumab and, if BRAF(V600) mutant-positive, a BRAF or

112 [SD 17.05] for placebo vs 18.17 [28.35] for ipilimumab) and insomnia (15.17 [22.53] vs 25.60 [29.19]

113 olumab (anti-programmed death-1 antibody) to ipilimumab (anti-cytotoxic T-cell lymphocyte-associated

114 Nivolumab followed by ipilimumab appears to be a more clinically beneficial op

115 Nine (2%) deaths occurred in the ipilimumab arm due to treatment-related AEs; no deaths o

116 combination arm and 18 patients (18%) in the ipilimumab arm had an objective response (odds ratio, 2.

117 months (95% CI, 24.5 to 32.5 months) in the ipilimumab arm versus 29.7 months (95% CI, 26.1 to 34.2

118 gression-free survival was 5.6 months in the ipilimumab arm versus 3.8 with placebo arm (hazard ratio

119 e combination arm and 23% of patients in the ipilimumab arm.

120 and efficacy results from the nivolumab plus ipilimumab arms of the study are presented.

121 y and activity of combination nivolumab plus ipilimumab as first-line therapy for NSCLC.

122 ate, the majority of our knowledge regarding ipilimumab-associated side effects is based upon clinica

123 tients were randomly assigned 1:1 to receive ipilimumab at 10 mg/kg plus dacarbazine (n = 250) or pla

124 reexisting autoimmune disorders who received ipilimumab at 9 academic tertiary referral centers from

125 lanoma, we randomly assigned them to receive ipilimumab at a dose of 10 mg per kilogram (475 patients

126 anced melanoma, this phase 3 trial evaluated ipilimumab at a dose of 10 mg per kilogram in patients w

127 nt therapy for high-risk stage III melanoma, ipilimumab at a dose of 10 mg per kilogram resulted in s

128 ose of 1 mg per kilogram of body weight plus ipilimumab at a dose of 3 mg per kilogram every 3 weeks

129 per kilogram every 2 weeks plus placebo; or ipilimumab at a dose of 3 mg per kilogram every 3 weeks

130 Patients received induction therapy with ipilimumab at a dose of 3 or 10 mg per kilogram of body

131 trial that compared the checkpoint inhibitor ipilimumab at doses of 0.3 mg, 3 mg, and 10 mg per kilog

132 The risk-benefit ratio of adjuvant ipilimumab at this dose and schedule requires additional

133 ry 2 weeks or every 3 weeks or four doses of ipilimumab (at 3 mg per kilogram) every 3 weeks.

134 se-escalating safety phase for the nivolumab/ipilimumab combination beginning at nivolumab 1 mg/kg pl

135 ) of 94 patients who received nivolumab plus ipilimumab compared with nine (20%) of 46 patients who r

136 Investigator-reported toxic effects of ipilimumab consisted mainly of skin, gastrointestinal, e

137 This structure reveals that ipilimumab contacts the front beta-sheet of CTLA-4 and i

138 toxic T-lymphocyte-associated protein 4 with ipilimumab could restore antitumor reactivity through a

139 Conclusion Ipilimumab did not improve OS in patients with metastati

140 atients received all four pembrolizumab plus ipilimumab doses; 64 (42%) remained on pembrolizumab mon

141 Because ipilimumab enhances T-cell responses, we hypothesized th

142 gned to receive nivolumab every 2 weeks plus ipilimumab every 12 weeks (n=38) or nivolumab every 2 we

143 izumab every 3 weeks (n=277), or intravenous ipilimumab every 3 weeks (ipilimumab for four doses; n=2

144 weeks (n=38) or nivolumab every 2 weeks plus ipilimumab every 6 weeks (n=40).

145 ts were reported in 12 (32%) patients in the ipilimumab every-12-weeks cohort and 11 (28%) patients i

146 p times of 12.8 months (IQR 9.3-15.5) in the ipilimumab every-12-weeks cohort and 11.8 months (6.7-15

147 events occurred in 14 (37%) patients in the ipilimumab every-12-weeks cohort and 13 (33%) patients i

148 e achieved in 12 (57%) of 21 patients in the ipilimumab every-12-weeks cohort and 13 (57%) of 23 pati

149 d in 18 (47% [95% CI 31-64]) patients in the ipilimumab every-12-weeks cohort and 15 (38% [95% CI 23-

150 off on Jan 7, 2016, 29 (76%) patients in the ipilimumab every-12-weeks cohort and 32 (82%) in the ipi

151 ients actually received treatment (38 in the ipilimumab every-12-weeks cohort; 39 in the ipilimumab e

152 ab every-12-weeks cohort and 32 (82%) in the ipilimumab every-6-weeks cohort had discontinued treatme

153 One patient in the ipilimumab every-6-weeks cohort was excluded before trea

154 ipilimumab every-12-weeks cohort; 39 in the ipilimumab every-6-weeks cohort).

155 ks cohort and 13 (57%) of 23 patients in the ipilimumab every-6-weeks cohort.

156 eks cohort and 11.8 months (6.7-15.9) in the ipilimumab every-6-weeks cohort.

157 and 15 (38% [95% CI 23-55]) patients in the ipilimumab every-6-weeks cohort; median duration of resp

158 limumab (n=70) or to the reverse sequence of ipilimumab followed by nivolumab (n=70), of whom 68 and

159 95% CI 37.6-62.4] of 68 patients) and in the ipilimumab followed by nivolumab group (30 [43%; 31.1-55

160 hieved 12-month overall survival than in the ipilimumab followed by nivolumab group (76%; 95% CI 64-8

161 llow-up of 14.7 months (IQR 5.6-23.9) in the ipilimumab followed by nivolumab group, median overall s

162 combination with four doses of reduced-dose ipilimumab followed by standard-dose pembrolizumab has a

163 7), or intravenous ipilimumab every 3 weeks (ipilimumab for four doses; n=278).

164 g treatment with the CTLA4-blocking antibody ipilimumab for metastatic melanoma.

165 he same event and five (3%) who discontinued ipilimumab for one event and later discontinued pembroli

166 igands is a major mechanistic contributor to ipilimumab function.

167 ed at least 5 years and continued to receive ipilimumab, grade 3 or 4 immune-related adverse events w

168 25 were similar in the nivolumab followed by ipilimumab group (34 [50%; 95% CI 37.6-62.4] of 68 patie

169 was not reached in the nivolumab followed by ipilimumab group (95% CI 23.7-not reached), whereas over

170 b group, as compared with 19.9 months in the ipilimumab group (hazard ratio for death with nivolumab

171 ion of patients in the nivolumab followed by ipilimumab group achieved 12-month overall survival than

172 -50.8) patients in the nivolumab followed by ipilimumab group and 43 (61%; 49.0-72.8) patients in the

173 e randomly assigned to treatment: 475 in the ipilimumab group and 476 in the placebo group.

174 ate at 3 years was 58% in the nivolumab-plus-ipilimumab group and 52% in the nivolumab group, as comp

175 r 4 occurred in 41.6% of the patients in the ipilimumab group and in 2.7% of those in the placebo gro

176 r 4 occurred in 54.1% of the patients in the ipilimumab group and in 26.2% of those in the placebo gr

177 l and overall survival in the nivolumab-plus-ipilimumab group and in the nivolumab group versus the i

178 l had not been reached in the nivolumab-plus-ipilimumab group and was 37.6 months in the nivolumab gr

179 ee survival, was significantly longer in the ipilimumab group than in the placebo group.

180 al was 26.1 months (95% CI 19.3-39.3) in the ipilimumab group versus 17.1 months (95% CI 13.4-21.6) i

181 survival was 46.5% (95% CI 41.5-51.3) in the ipilimumab group versus 34.8% (30.1-39.5) in the placebo

182 tis (ten [15%]) in the nivolumab followed by ipilimumab group vs 14 [20%] in the reverse sequence gro

183 olizumab 2 week group and 22 patients in the ipilimumab group withdrew consent and did not receive tr

184 D 19] in the placebo group vs 72 [22] in the ipilimumab group) and week 10 (77 [20] vs 70 [23]).

185 In the ipilimumab group, 5 patients (1.1%) died owing to immune

186 of recurrence-free survival was 40.8% in the ipilimumab group, as compared with 30.3% in the placebo

187 is-free survival at 5 years was 48.3% in the ipilimumab group, as compared with 38.9% in the placebo

188 overall survival at 5 years was 65.4% in the ipilimumab group, as compared with 54.4% in the placebo

189 in 59% of the patients in the nivolumab-plus-ipilimumab group, in 21% of those in the nivolumab group

190 oup, 55% in the 3-week group, and 43% in the ipilimumab group.

191 group and in the nivolumab group versus the ipilimumab group.

192 nivolumab group, as compared with 34% in the ipilimumab group.

193 nivolumab group, and in 28% of those in the ipilimumab group.

194 ETATION: In NSCLC, first-line nivolumab plus ipilimumab had a tolerable safety profile and showed enc

195 In NSCLC, first-line nivolumab plus ipilimumab had a tolerable safety profile and showed enc

196 T-VEC with ipilimumab had a tolerable safety profile, and the combi

197 The combination of nivolumab and ipilimumab has a higher rate of irAEs than either approa

198 e immune checkpoint inhibitors nivolumab and ipilimumab has shown greater efficacy than either agent

199 identified as non-responders to anti-CTLA-4 (ipilimumab) have tumors with genomic defects in IFN-gamm

200 pembrolizumab group and was 16.0 months with ipilimumab (hazard ratio [HR] 0.68, 95% CI 0.53-0.87 for

201 Nine years after treatment with ipilimumab, he is alive and shows no evidence of melanom

202 nivolumab in combination with standard-dose ipilimumab improves objective response and progression-f

203 led to discontinuation of pembrolizumab and ipilimumab in 22 (14%) patients, including 17 (11%) who

204 demonstrate a durable survival benefit with ipilimumab in advanced melanoma.

205 We evaluated treatment with ipilimumab in asymptomatic or minimally symptomatic pati

206 elanoma who received nivolumab combined with ipilimumab in clinical trials discontinued treatment bec

207 ed the efficacy and safety of nivolumab plus ipilimumab in combination, and nivolumab plus a tyrosine

208 ss the efficacy and safety of nivolumab plus ipilimumab in patients who discontinued treatment becaus

209 ession-free survival of pembrolizumab versus ipilimumab in patients with advanced melanoma.

210 al and had less high-grade toxicity than did ipilimumab in patients with advanced melanoma.

211 stigated the combination of TriMixDC-MEL and ipilimumab in patients with pretreated advanced melanoma

212 tudy to determine the safety and efficacy of ipilimumab in patients with relapsed hematologic cancer

213 and activity of nivolumab and nivolumab plus ipilimumab in patients with SCLC who progressed after on

214 e evaluation of nivolumab and nivolumab plus ipilimumab in phase 3 randomised controlled trials in SC

215 his study was initiated, the clinical use of ipilimumab in refractory patients with unmet medical nee

216 Adjuvant treatment with ipilimumab in this setting was approved in October, 2014

217 ) of 94 patients who received nivolumab plus ipilimumab (including colitis in ten [11%] of 94 patient

218 Purpose Ipilimumab increases antitumor T-cell responses by bindi

219 Immune checkpoint therapies, such as ipilimumab, induce dramatic antitumor responses in a sub

220 ll repertoire to a limited number of clones, ipilimumab induced greater diversification in the T-cell

221 tions of autoimmune disease and conventional ipilimumab-induced irAEs that were readily manageable wi

222 concurrent therapy with nivolumab (NIVO) and ipilimumab (IPI) in patients with previously treated or

223 Ipilimumab is a fully human antibody targeting CTLA-4 th

224 Ipilimumab is a standard treatment for metastatic melano

225 Ipilimumab is the first-in-class immunotherapeutic for b

226 The immune checkpoint inhibitor ipilimumab is the standard-of-care treatment for patient

227 The combination of TriMixDC-MEL and ipilimumab is tolerable and results in an encouraging ra

228 tandard-dose pembrolizumab plus reduced-dose ipilimumab might be a tolerable, efficacious treatment o

229 the combination of first-line nivolumab plus ipilimumab might lead to improved outcomes compared with

230 o have greater efficacy than either T-VEC or ipilimumab monotherapy.

231 combined treatment was comparable to that of ipilimumab monotherapy.

232 atients who received nivolumab combined with ipilimumab (n = 35, mucosal melanoma; n = 326, cutaneous

233 ly assigned to talimogene laherparepvec plus ipilimumab (n = 98), or ipilimumab alone (n = 100).

234 2011, 951 patients were randomly assigned to ipilimumab (n=475) or placebo (n=476), all of whom were

235 d randomly assigned to nivolumab followed by ipilimumab (n=70) or to the reverse sequence of ipilimum

236 ed] and 520 from randomized cohorts [n = 226 ipilimumab naive; n = 294 ipilimumab treated]).

237 nts (135 from a nonrandomized cohort [n = 87 ipilimumab naive; n = 48 ipilimumab treated] and 520 fro

238 Patients and Methods Patients with ipilimumab-naive or -treated advanced/metastatic melanom

239 lanoma, who progressed on ipilimumab or were ipilimumab-naive, before and after nivolumab initiation

240 ected stage III MMel patients after adjuvant ipilimumab + nivolumab (but not nivolumab alone).

241 12 (8%) patients discontinued ipilimumab only and 14 (9%) discontinued pembrolizumab o

242 1:1 to receive talimogene laherparepvec plus ipilimumab or ipilimumab alone.

243 atment, suggesting its improvement by adding ipilimumab or other strategies of Treg ablation to promo

244 the average score reported during induction (ipilimumab or placebo at a dose of 10 mg/kg, administere

245 ts with advanced melanoma, who progressed on ipilimumab or were ipilimumab-naive, before and after ni

246 with combination therapy with nivolumab plus ipilimumab or with nivolumab alone than with ipilimumab

247 To date, anti-CTLA-4 (ipilimumab) or anti-PD-1 (nivolumab) monotherapy has not

248 melanoma to nivolumab alone, nivolumab plus ipilimumab, or ipilimumab alone.

249 tial administration of nivolumab followed by ipilimumab, or the reverse sequence, could improve safet

250 0.53-0.86 for pembrolizumab every 3 weeks vs ipilimumab; p=0.0008).

251 0.53-0.87 for pembrolizumab every 2 weeks vs ipilimumab; p=0.0009 and 0.68, 0.53-0.86 for pembrolizum

252 I, 13.6% to 23.4%) for patients treated with ipilimumab plus dacarbazine versus 8.8% (95% CI, 5.7% to

253 quently, patients assigned to nivolumab plus ipilimumab received nivolumab 3 mg/kg every 2 weeks unti

254 a new standard of care for the treatment of ipilimumab-refractory melanoma.

255 ponse compared with chemotherapy regimens in ipilimumab-refractory patients with advanced melanoma.

256 afety profile of the approved nivolumab plus ipilimumab regimen.

257 Nivolumab combined with ipilimumab resulted in longer progression-free survival

258 c melanoma, nivolumab alone or combined with ipilimumab resulted in significantly longer progression-

259 lts from this trial show that treatment with ipilimumab results in longer recurrence-free survival co

260 seven patients received subsequent doses of ipilimumab safely, the majority with premedication.

261 Nivolumab combined with ipilimumab seemed to have greater efficacy than either a

262 Nivolumab monotherapy and nivolumab plus ipilimumab showed antitumour activity with durable respo

263 s who had received anti-CTLA4 immunotherapy (ipilimumab) showed upregulation of an IFNG-response gene

264 phase Ib trial of T-VEC in combination with ipilimumab, T-VEC was administered intratumorally in wee

265 In ex vivo assays, ipilimumab targeted CTLA-4(+) Treg and restored cytolyti

266 Because ipilimumab targets T lymphocytes and not the tumor itsel

267 were more immune-related adverse events with ipilimumab than with placebo.

268 eek 25 was higher with nivolumab followed by ipilimumab than with the reverse sequence (28 [41%; 95%

269 rts enrolling 190 MMel patients treated with ipilimumab, that PD-L1 expression on peripheral T cells

270 Conclusion Nivolumab plus ipilimumab therapy demonstrated manageable safety, notab

271 s are common, and the safety and efficacy of ipilimumab therapy in patients with preexisting autoimmu

272 Ipilimumab therapy may be considered in this setting wit

273 of immune-related adverse effects related to ipilimumab therapy, dermatomyositis associated with this

274 ressive therapy at the time of initiation of ipilimumab therapy, most commonly low-dose prednisone or

275 inhibitory pathway in prostate tumors after ipilimumab therapy.

276 responsible for the selectivity exhibited by ipilimumab toward CTLA-4 relative to the homologous and

277 ized cohort [n = 87 ipilimumab naive; n = 48 ipilimumab treated] and 520 from randomized cohorts [n =

278 d cohorts [n = 226 ipilimumab naive; n = 294 ipilimumab treated]).

279 ed adverse event (AE) reported in >/= 10% of ipilimumab-treated patients.

280 microenvironment, we evaluated untreated and ipilimumab-treated tumors from patients in a presurgical

281 patients with metastatic melanoma undergoing ipilimumab treatment and correlate the pre-inflammation

282 present predictors of survival benefit after ipilimumab treatment as well as therapeutic targets.

283 een patients who discontinued nivolumab plus ipilimumab treatment because of AEs during the induction

284 g T cells, we examined in this study whether ipilimumab treatment leads to clonal expansion of tissue

285 With ipilimumab treatment, 8 patients (27%) experienced exace

286 Specifically, ipilimumab triggered increases in the numbers of clonoty

287 regimens of pembrolizumab, or one regimen of ipilimumab, using a centralised, computer-generated allo

288 combination of talimogene laherparepvec plus ipilimumab versus ipilimumab alone in patients with adva

289 ly higher with talimogene laherparepvec plus ipilimumab versus ipilimumab alone.

290 (hazard ratio for death with nivolumab plus ipilimumab vs. ipilimumab, 0.55 [P<0.001]; hazard ratio

291 atients treated with nivolumab combined with ipilimumab was 5.9 months (95% CI, 2.8 months to not rea

292 Ipilimumab was clinically active and was associated with

293 e 3 study, nivolumab alone or nivolumab plus ipilimumab was compared with ipilimumab alone in patient

294 rly-phase data showed that administration of ipilimumab was feasible in patients with recurrent hemat

295 HD) that precluded further administration of ipilimumab was observed in 4 patients (14%).

296 Prostate-specific antigen responses to ipilimumab were also associated with increased T-cell di

297 Two courses of ipilimumab were each followed by a clinical episode of M

298 y crystal structure of the complex formed by ipilimumab with its human CTLA-4 target.

299 EORTC 18071 phase 3 trial compared adjuvant ipilimumab with placebo in patients with stage III melan

300 to provide superior overall survival versus ipilimumab, with no difference between pembrolizumab dos