Details of data from NSCLC clinical trials

Investigated (inv)

Comparator (comp)

NIVO+IPIL

chemo

583

Phase:

3

Randomisation:

Open label

Primary tumour:

NSCLC

Subtype (biomarker):

Any

Stage:

Line of therapy:

L1

Primary

NIVO+IPIL

chemo

HR

p

OS PD-L1≥1%

17.1 mo

14.9 mo

0.79 (0.65–0.96)

0.007 OS

—

Secondaries

NIVO+IPIL

chemo

HR

p

OS any PD-L1

17.1 mo

13.9 mo

0.73 (0.64–0.84)

—

DoR PD-L1≥1%

23.2 mo

6.2 mo

—

OS PD-L1<1%

17.2 mo

12.2 mo

0.62 (0.49–0.79)

—

PFS

7.2 mo

5.5 mo

0.58 (0.41-0.81)

<0.001

(all grades, %)

NIVO+IPIL

chemo

p

Any AE grade 3-4

31.2

36.1 NA

AE leading to discontinuation

17.4

8.9 NA

Rash

16.7

5.1 NA

Diarrhea

16.3

9.6 NA

Pruritus

14.1

0.9 NA

Hypothyroidism

11.6

0.0 NA

Nausea

9.7

36.0 NA

Vomiting

4.7

13.3 NA

Anemia

4.0

32.1 NA

Neutropenia

0.2

17.0 NA

Constipation

4.0

15.1 NA

—

Inclusion
Exclusion

- Subjects with histologically confirmed Stage IV or recurrent NSCLC squamous or non-squamous histology, with no prior systemic anticancer therapy - Subjects must have programmed death-ligand 1 (PD -L1) immunohistochemical (IHC) testing, with results, performed by the central lab during the Screening period - Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 1 - Measurable disease by CT or MRI per response evaluation criteria in solid tumors version 1.1 (RECIST 1.1) criteria Other protocol defined inclusion/exclusion criteria apply

- Subjects with untreated Central nervous system (CNS) metastases are excluded - Subjects with an active, known or suspected autoimmune disease are excluded - Any positive test for hepatitis B virus or hepatitis C virus or human immunodeficiency virus (HIV) indicating acute or chronic infection Other protocol defined inclusion/exclusion criteria apply

Characteristics

NIVO+IPIL

chemo

Age - no.(%)

Median (range)dc-comma yr

64.0 (26-87)

64.0 (29-87)

<65

306 (52.5)

305 (52.3)

≥65 to <75

219 (37.6)

223 (38.3)

≥75

58 (9.9)

55 (9.4)

Sex - no.(%)

Male

393 (67.4)

385 (66.0)

Female

190 (32.6)

198 (34.0)

—

Region - no.(%)

North America

56 (9.6)

70 (12.0)

Europe

302 (51.8)

293 (50.3)

Asia

121 (20.8)

124 (21.3)

Rest of the world

104 (17.8)

96 (16.5)

ECOG PS - no.(%)

0 204 (35.0)

191 (32.8)

1 377 (64.7)

386 (66.2)

≥2

2 (0.3)

4 (0.7)

Not reported

0 2 (0.3)

Smoking status - no.(%)

Never smoked

79 (13.6)

78 (13.4)

Current or former smoker

497 (85.2)

499 (85.6)

Unknown

7 (1.2)

6 (1.0)

—

Tumor histologic type - no.(%)

Squamous

163 (28.0)

162 (27.8)

Nonsquamous

419 (71.9)

421 (72.2)

Not reported

1 (0.2)

0 —

—

Metastasis - no.(%)

Liver

122 (20.9)

130 (22.3)

Bone

163 (28.0)

153 (26.2)

CNS

64 (11.0)

51 (8.7)

—

PD-L1 status - no.(%)

<1%

187 (32.1)

186 (31.9)

≥1%

396 (67.9)

397 (68.1)

1-49%

191 (32.8)

205 (35.2)

≥50%

205 (35.2)

192 (32.9)

TMB - no.(%)

Patients evaluated

330 (56.6)

349 (59.9)

≥10 mut/Mb

139 (42.1)

160 (45.8)

<10 mut/Mb

191 (57.9)

189 (54.2)

—

Ad-hoc:

no.pts inv.

no.pts comp.

NIVO+IPIL

chemo

HR

p

PFS @1yr TMB high

139

160 43%

13%

0.58 (0.41–0.81)

<0.001

PFS@1yr PD-L1≥1%

101

112 42%

16%

0.62 (0.44–0.88)

—

PFS@1yr PD-L1<1%

38

48 45%

8%

0.48 (0.27–0.85)

—

OS PD-L1≥1%
OS

analisys of OS PD-L1≥1%

NIVO+IPIL

chemo

HR (95% CI)

Agedc-comma yr

<65 (n=406)

19.7 mo

16.0 mo

0.70 (0.55–0.89)

65 to <75 (n=306)

16.6 mo

14.5 mo

0.91 (0.70–1.19)

Sex

Male (n=515)

18.7 mo

14.0 mo

0.75 (0.61–0.93)

Female (n=278)

16.6 mo

16.2 mo

0.91 (0.69–1.21)

ECOG

0 (n=269)

24.4 mo

17.5 mo

0.66 (0.48–0.89)

1 (n=519)

14.6 mo

12.7 mo

0.89 (0.73–1.09)

Tumor histologic type

Squamous (n=236)

14.8 mo

9.2 mo

0.69 (0.52–0.92)

Nonsquamous (n=557)

19.4 mo

17.2 mo

0.85 (0.69–1.04)

Liver metastases

Yes (n=156)

9.5 mo

11.9 mo

1.05 (0.74–1.49)

No (n=637)

19.9 mo

16.3 mo

0.76 (0.63–0.92)

Bone metastases

Yes (n=208)

13.4 mo

10.0 mo

0.75 (0.55–1.03)

No (n=585)

18.8 mo

16.7 mo

0.81 (0.67–0.99)

CNS metastases

Yes (n=81)

16.8 mo

13.4 mo

0.68 (0.41–1.11)

No (n=712)

17.1 mo

14.9 mo

0.82 (0.68–0.98)

Smoking status

Never smoked

15.2 mo

19.6 mo

1.23 (0.76–1.98)

Current or former smoker

18.1 mo

14.1 mo

0.77 (0.64–0.92)

—

analisys of OS

NIVO+IPIL

chemo

HR (95% CI)

PD-L1 expression level (ITT)

≥1%

17.1 mo

14.9 mo

0.79 (0.65–0.96)

<1%

17.2 mo

12.2 mo

0.62 (0.49–0.79)

PD-L1 expression level

1-49%

15.1 mo

0.94 (0.75–1.18)

≥50%

21.2 mo

14.0 mo

0.70 (0.55–0.90)

Tumor mutational burden

Lowdc-comma <10 mut/Mb

16.2 mo

12.6 mo

0.75 (0.59–0.94)

Highdc-comma ≥10 mut/Mb

23.0 mo

16.4 mo

0.68 (0.51–0.91)

PD-L1<1% dc-and TMB

TMB <10 mut/Mb

15.5 mo

13.0 mo

0.69 (0.46–1.05)

TMB ≥10 mut/Mb

20.4 mo

11.2 mo

0.51 (0.30–0.87)

PD-L1≥1% dc-and TMB

TMB <10 mut/Mb

16.2 mo

12.1 mo

0.78 (0.59–1.02)

TMB ≥10 mut/Mb

24.4 mo

18.1 mo

0.77 (0.54–1.09)

PD-L1≥50% dc-and TMB

TMB <10 mut/Mb

18.1 mo

8.1 mo

0.67 (0.44–1.03)

TMB ≥10 mut/Mb

NR

17.2 mo

0.63 (0.37–1.07)

—

NSCLC: CheckMate 227 trial

EMA SPC links

2018-05-31

M.D. Hellmann

Nivolumab plus Ipilimumab in Lung Cancer with a High Tumor Mutational Burden

2019-11-21

M.D. Hellmann

Nivolumab plus Ipilimumab in Advanced Non–Small-Cell Lung Cancer

Investigated (inv)

Comparator (comp)

Randomisation:

Primary tumour:

Subtype (biomarker):

Stage:

Line of therapy:

Primary

NIVO+IPIL

chemo

HR

p

OS PD-L1≥1%

17.1 mo

14.9 mo

0.79 (0.65–0.96)

0.007

OS

—

—

—

—

Secondaries

NIVO+IPIL

chemo

HR

p

OS any PD-L1

17.1 mo

13.9 mo

0.73 (0.64–0.84)

—

DoR PD-L1≥1%

23.2 mo

6.2 mo

—

—

OS PD-L1<1%

17.2 mo

12.2 mo

0.62 (0.49–0.79)

—

PFS

7.2 mo

5.5 mo

0.58 (0.41-0.81)

<0.001

(all grades, %)

NIVO+IPIL

chemo

p

Any AE grade 3-4

31.2

36.1

NA

AE leading to discontinuation

17.4

8.9

NA

Rash

16.7

5.1

NA

Diarrhea

16.3

9.6

NA

Pruritus

14.1

0.9

NA

Hypothyroidism