Nivolumab immune checkpoint inhibition

Description Results

OS 0.63 [0.51; 0.78] median 5.26 vs. 4.14

nivolumab at 3 mg/kg every 2 weeks (n=330)

vs.

placebo (n=163)

double blind

Parallel groups

Sample size: 330/163

Primary endpoint: OS

FU duration:

OS 0.70 [0.51; 0.96] median 7.5 mo vs. 5.1 mo Demonstrated

PFS 0.89 [0.70; 1.13] median 2.0 mo vs. 2.3 mo

nivolumab (at a dose of 3 mg per kilogram of body weight) every 2 weeks (n=361)

vs.

standard, single-agent systemic therapy (methotrexate, docetaxel, or cetuximab). (n=0)

open-label

Parallel groups

Sample size: 361/0

Primary endpoint: overall survival

FU duration:

overall survival 0.73 [0.59; 0.90] median 12.2 mo vs. 9.4 mo

grade 3–5 drug-related AEs 0.19 [0.14; 0.28]

PFS 0.92 [0.77; 1.10] median 2.3 mo vs. 4.2 mo

overall survival 1.02 [0.80; 1.30] median 14.4 mo vs. 13.2 mo

PFS 1.15 [0.91; 1.45] median 4.2 mo vs. 5.9 mo

overall survival 0.59 [0.44; 0.79] median 9.2 mo vs. 6.0 mo

PFS 0.62 [0.47; 0.81] median 3.5 mo vs. 2.8 mo

ORR 2.28 [1.21; 4.32]

grade 3–5 drug-related AEs 0.12 [0.07; 0.24]

Endocrine disorders ∞ [NaN; ∞]

Hypothyroidism ∞ [NaN; ∞]

Pneumonitis or interstitial lung disease 6.89 [0.86; 55.24]

Severe skin reactions 1.07 [0.49; 2.35]

Colitis ∞ [NaN; ∞]

PFS 0.58 [0.41; 0.82] median 7.2 mo vs. 5.5 mo

PFS 0.74 [0.58; 0.94] median 5.6 vs. 4.7

Nivolumab 3 mg/kg solution intravenously every 2 weeks until documented disease progression (n=292)

vs.

Docetaxel 75 mg/m² concentrate for solution for intravenous infusion every 3 weeks until documented disease progression (n=290)

open

Parallel groups

Sample size: 292/290

Primary endpoint: OS

FU duration:

Nivolumab solution for Injection 3 mg/kg Intravenous every 2 weeks until disease progression (n=271)

vs.

platinum-based chemotherapy (administered once every 3 weeks for up to six cycles). (n=270)

Patients who progressed on chemotherapy could crossover to nivolumab as second line treatment.

open design

Parallel groups

Sample size: 271/270

Primary endpoint: PFS

FU duration:

cross over were permitted, a total of 128 of 212 patients (60%) in the chemotherapy group received nivolumab as subsequent therapy

Nivolumab 3 mg/kg solution intravenously every 2 weeks until documented disease progression (n=135)

vs.

Docetaxel 75 mg/m2 solution intravenously every 3 weeks until documented disease progression (n=137)

open

Sample size: 135/137

Primary endpoint: OS

FU duration:

nivolumab plus ipilimumab (n=139)

vs.

chemotherapy (n=160)

4 arms: Nivolumab, or Nivolumab Plus Ipilimumab, or Nivolumab Plus Platinum-doublet Chemotherapy, Compared to Platinum Doublet Chemotherapy

Tumor mutational burden was determined by the FoundationOne CDx assay

No masking

Parallel groups

Sample size: 139/160

Primary endpoint: PFS, OS

FU duration:

Nivolumab + chemotherapy (n=177)

vs.

chemotherapy (n=186)

4 arms: Nivolumab, or Nivolumab Plus Ipilimumab, or Nivolumab Plus Platinum-doublet Chemotherapy, Compared to Platinum Doublet Chemotherapy

No masking

Sample size: 177/186

Primary endpoint: Overall survival (OS)

FU duration:

PFS 0.42 [0.31; 0.57] median 11.5 mo vs. 2.9 mo Demonstrated

Adverse events leading to discontinuation of drug 2.46 [1.82; 3.34]

Grade 3 or 4 drug-related adverse events 2.01 [1.63; 2.47]

OS 0.42 [0.25; 0.71] median not reached vs. 10.8 mo Demonstrated

PFS 0.43 [0.34; 0.55] median 5.1 mo vs. 2.2 mo

Vitiligo any grade 21.89 [2.98; 160.92]

Adverse events leading to discontinuation of drug 0.58 [0.31; 1.09]

Grade 3 or 4 drug-related adverse events 0.66 [0.41; 1.07]

Vitiligo grade 3-4 NaN [NaN; NaN]

overall response rate 3.72 [1.41; 9.85]

Grade 3 or 4 drug-related adverse events 0.29 [0.18; 0.46]

recurrence free survival 0.65 [0.51; 0.83] Demonstrated

PFS 0.65 [0.51; 0.83]

Adverse events leading to discontinuation of drug 0.23 [0.17; 0.31]

Grade 3 or 4 drug-related adverse events 0.31 [0.24; 0.40]

PFS 0.57 [0.43; 0.76] median 6.9 mo vs. 2.9 mo Demonstrated

Adverse events leading to discontinuation of drug 0.52 [0.32; 0.83]

Grade 3 or 4 drug-related adverse events 0.60 [0.44; 0.81]

PFS 0.65 [0.51; 0.82]

recurrence free survival 0.65 [0.51; 0.82]

distant metastasis free survival 0.73 [0.56; 0.96]

1mg of nivolumab per kilogram every 3 weeks plus 3 mg of ipilimumab per kilogram every 3 weeks for 4 doses, followed by 3 mg of nivolumab per kilogram every 2 weeks for cycle 3 and beyond (n=314)

vs.

3 mg of ipilimumab per kilogram every 3 weeks for 4 doses (n=315)

3 arms: nivolumab alone, nivolumab combined with ipilimumab, ipilumab alone

double-blind

Parallel groups

Sample size: 314/315

Primary endpoint: PFS, OS

FU duration:

nivolumab at a dose of 3 mg per kilogram of body weight every 2 weeks (n=210)

vs.

dacarbazine at a dose of 1000 mg per square meter of body-surface area every 3 weeks (n=208)

double-blind

Parallel groups

Sample size: 210/208

Primary endpoint: OS

FU duration:

ntravenous infusion of nivolumab 3 mg/kg every 2 weeks until progression or unacceptable toxic eff ects (n=272)

vs.

investigator’s choice of chemotherapy (dacarbazine 1000 mg/m² every 3 weeks or paclitaxel 175 mg/m² combined with carboplatin area under the curve 6 every 3 weeks) (n=133)

open-label

Parallel groups

Sample size: 272/133

Primary endpoint: ORR, OS

FU duration:

phase 3

nivolumab at a dose of 3 mg per kilogram of body weight every 2 weeks (n=453)

vs.

ipilimumab at a dose of 10 mg per kilogram every 3 weeks for four doses and then every 12 weeks (n=453)

double-blind

Parallel groups

Sample size: 453/453

Primary endpoint: Recurrence free survival

FU duration: 18 months (median)

nivolumab (1 mg per kilogram)and ipilimumab (3 mg per kilogram of body weight) combined once every 3 weeks for four doses followed by nivolumab (3 mg per kilogram) every 2 weeks until the occurrence of disease progression or unacceptable toxic effects (n=-9)

vs.

(n=-9)

double-blind

Parallel groups

Sample size: -9/-9

Primary endpoint: investigator-assessed, confirmed objective response

FU duration:

phase 2. The primary end point was the rate of investigator-assessed, confirmed objective response among patients with BRAF V600 wild-type tumors

3 mg of nivolumab per kilogram of body weight every 2 weeks (n=316)

vs.

3 mg of ipilimumab per kilogram every 3 weeks for 4 doses (n=315)

3 arms: nivolumab alone, nivolumab combined with ipilimumab, ipilumab alone

double-blind

Parallel groups

Sample size: 316/315

Primary endpoint: PFS, OS

FU duration:

Nivolumab + ipilumab (n=314)

vs.

nivolumab alone (n=316)

3 arms: nivolumab alone, nivolumab combined with ipilimumab, ipilumab alone

double-blind

Parallel groups

Sample size: 314/316

Primary endpoint: PFS, OS

FU duration:

this comparison (nivo+ipi versus nivo) was not planned and could not be considered as interential

(n=-9)

vs.

(n=-9)

Sample size: -9/-9

Primary endpoint:

FU duration:

OS 0.73 [0.57; 0.93] median 25.0 mo vs. 19.6 mo

PFS 0.88 [0.75; 1.03] median 4.6 mo vs. 4.4 mo

OS 0.68 [0.49; 0.95] median not reached vs. 32.9 mo Demonstrated

PFS 0.82 [0.64; 1.05] median 11.56 mo vs. 8.38 mo

3 mg of nivolumab per kilogram of body weight intravenously every 2 weeks (n=-9)

vs.

10-mg everolimus tablet orally once daily (n=-9)

open-label

Parallel groups

Sample size: -9/-9

Primary endpoint: OS

FU duration:

nivolumab 3 mg/kg plus ipilimumab 1 mg/kg every 3 weeks for 4 doses followed by Opdivo 3 mg/kg every 2 weeks (n=-9)

vs.

sunitinib 50 mg once daily for 4 weeks, followed by 2 weeks off before continuation of treatment (n=-9)

open-label

Parallel groups

Sample size: -9/-9

Primary endpoint: ORR, PFS, OS

FU duration:

phase 3

nivolumab 3 mg/kg intravenously every 2 weeks until disease progression and clinical deterioration, unacceptable toxicity, or other protocol-defined reasons (n=270)

vs.

(n=-9)

Single-arm study

Sample size: 270/-9

Primary endpoint: ORR

FU duration: