Details of data from Melanoma clinical trials

Investigated (inv)

Comparator (comp)

NIVO

IPIL

453

Phase:

3

Randomisation:

Double blind

Primary tumour:

Melanoma

Subtype (biomarker):

Any

Stage:

early

Line of therapy:

ADJ

Primary

NIVO

IPIL

HR

p

RFS @1yr

70.5%

60.8%

0.65 (0.51-0.83)

<0.001

—

Secondaries

NIVO

IPIL

HR

p

RFS (PD-L1≥5%) @1yr

81.9%

73.8%

0.50 (0.32–0.78)

—

RFS (PD-L1<5%) @1yr

64.3%

53.7%

0.71 (0.56–0.91)

—

RFS @18mo.

66.4%

52.7%

—

dMFS @1yr

80.2%

73.4%

0.73 (0.55-0.95)

—

(all grades, %)

NIVO

IPIL

p

Any AE grade 3 or 4

25.4

55.2 NA

Treatment discontinuation due to AE

9.7

42.6 NA

Fatigue

34.5

32.9 NA

Diarrhea

24.3

45.9 NA

Pruritus

23.2

33.6 NA

Rash

19.9

29.4 NA

Nausea

15.0

20.1 NA

Hypothyroidism

10.8

6.8 NA

ALT increased

6.2

14.6 NA

AST increased

5.5

13.2 NA

Arthralgia

12.6

10.8 NA

Maculopapular rash

5.3

11.0 NA

Hypophysitis

1.5

10.6 NA

Pyrexia

1.5

11.9 NA

Inclusion
Exclusion

- At least 15 years of age Except: where local regulations and/or institutional policies do not allow for subjects < 18 years of age (pediatric population) to participate. For those sites, the eligible subject population is ≥ 18 years of age - Completely removed melanoma by surgery performed within 12 weeks of randomization - Stage IIIb/C or Stage IV before complete resection - No previous anti-cancer treatment Other protocol-defined inclusion/exclusion criteria apply

- Ocular or uveal melanoma - History of carcinomatosis meningitis - History of auto-immune disease - Treatment directed against the resected melanoma that is administrated after the surgery Other protocol-defined inclusion/exclusion criteria apply

Characteristics

NIVO

IPIL

Agedc-comma sex

Median age (range) yr

56 (19–83)

54 (18–86)

Male - no.(%)

258 (57.0)

269 (59.4)

Female - no.(%)

195 (43.0)

184 (40.6)

—

Disease stage - no.(%)

IIIB

163 (36.0)

148 (32.7)

IIIC

204 (45.0)

218 (48.1)

IV

82 (18.1)

87 (19.2)

Other or not reported

4 (1.0)

0 Lymph-node involvement in stage III — no./total no.(%)

Microscopic

125/369 (33.9)

134/366 (36.6)

Macroscopic

219/369 (59.3)

214/366 (58.5)

Not reported

25/369 (6.8)

18/366 (4.9)

—

Tumor ulceration in stage III - no./total no.(%)

Yes

153/369 (41.5)

135/366 (36.9)

No

201/369 (54.5)

216/366 (59.0)

Not reported

15/369 (4.1)

15/366 (4.1)

—

Metastasis status in stage IV - no./total no.(%)

M1a

50/82 (61.0)

51/87 (58.6)

M1b

12/82 (14.6)

15/87 (17.2)

M1c

20/82 (24.4)

21/87 (24.1)

—

Tumor PD-L1 expression - no.(%)

<5%

275 (60.7)

286 (63.1)

≥5%

152 (33.6)

154 (34.0)

Could not be determined or not reported

26 (5.7)

13 (2.9)

—

BRAF status - no.(%)

Mutation

187 (41.3)

194 (42.8)

No mutation

197 (43.5)

214 (47.2)

Not reported

69 (15.2)

45 (9.9)

—

Melanoma subtype - no.(%)

Cutaneous

388 (85.7)

378 (83.4)

Acral

16 (3.5)

17 (3.8)

Mucosal

16 (3.5)

13 (2.9)

Other

33 (7.3)

45 (9.9)

LDH level - no.(%)

≤ULN

413 (91.2)

411 (90.7)

>ULN

32 (7.1)

37 (8.2)

≤2x ULN

445 (98.2)

446 (98.5)

>2x ULN

0 2 (0.4)

Melanoma subtype – no.(%)

Cutaneous

388 (85.7)

378 (83.4)

Acral

16 (3.5)

17 (3.8)

Mucosal

16 (3.5)

13 (2.9)

Other

33 (7.3)

45 (9.9)

—

Ad-hoc:

no.pts inv.

no.pts comp.

NIVO

IPIL

HR

p

RFS (PD-L1≥5%) @1yr

152

154 81.9%

73.8%

0.50 (0.32–0.78)

—

RFS (PD-L1<5%) @1yr

275

286 64.3%

53.7%

0.71 (0.56–0.91)

—

RFS (IIIBdc-comma IIIC) @1yr

367

366 72.3%

61.6%

0.65 (0.51–0.82)

—

RFS @1yr
—

analisys of RFS @1yr

NIVO

IPIL

HR (95% CI)

Stage

IIIB

—

0.67 (0.44–1.00)

IIIC

—

0.65 (0.49–0.87)

Stage

IV M1a or M1b

—

0.63 (0.38–1.05)

IV M1c

—

1.00 (0.37–2.66)

Lymph-node involvement in stage III

Microscopic

—

0.71 (0.47–1.07)

Macroscopic

—

0.62 (0.46–0.84)

Ulceration according to lymph-node involvement in stage III

Presentdc-comma microscopic

—

1.00 (0.58–1.72)

Presentdc-comma macroscopic

—

0.55 (0.34–0.89)

Ulceration according to lymph-node involvement in stage III

Absentdc-comma microscopic

—

0.51 (0.27–0.96)

Absentdc-comma macroscopic

—

0.63 (0.43–0.94)

Subtype

Mucosal

—

1.57 (0.57–4.33)

Cutaneous

—

0.61 (0.48–0.77)

BRAF status

Mutation

—

0.72 (0.52–1.00)

No mutation

—

0.58 (0.43–0.79)

PD-L1 status

<5% or indeterminate

—

0.71 (0.56–0.90)

≥5%

—

0.50 (0.32–0.78)

Age

<65 yr

—

0.65 (0.51–0.84)

≥65 yr

—

0.66 (0.45–0.97)

Sex

Male

—

0.68 (0.53–0.88)

Female

—

0.63 (0.44–0.89)

analisys of —

NIVO

IPIL

HR (95% CI)

—

Melanoma: CheckMate 238 trial

EMA SPC links

2017-11-09

J. Weber

Adjuvant Nivolumab versus Ipilimumab in Resected Stage III or IV Melanoma

Investigated (inv)

Comparator (comp)

Randomisation:

Primary tumour:

Subtype (biomarker):

Stage:

Line of therapy:

Primary

NIVO

IPIL

HR

p

RFS @1yr

70.5%

60.8%

0.65 (0.51-0.83)

<0.001

—

—

—

—

—

Secondaries

NIVO

IPIL

HR

p

RFS (PD-L1≥5%) @1yr

81.9%

73.8%

0.50 (0.32–0.78)

—

RFS (PD-L1<5%) @1yr

64.3%

53.7%

0.71 (0.56–0.91)

—

RFS @18mo.

66.4%

52.7%

—

—

dMFS @1yr

80.2%

73.4%

0.73 (0.55-0.95)

—

(all grades, %)

NIVO

IPIL

p

Any AE grade 3 or 4

25.4

55.2

NA

Treatment discontinuation due to AE

9.7

42.6

NA

Fatigue

34.5

32.9

NA

Diarrhea

24.3

45.9

NA

Pruritus

23.2

33.6

NA

Rash

19.9

29.4

NA