Details of data from Melanoma clinical trials

Investigated (inv)

Comparator (comp)

NIVO

DACA

210

208

Phase:

3

Randomisation:

Double blind

Primary tumour:

Melanoma

Subtype (biomarker):

Any

Stage:

Line of therapy:

L1

Primary

NIVO

DACA

HR

p

OS (@1yr)

72.9 %

42.1%

0.42 (0.25-0.73)

<0.001

—

Secondaries

NIVO

DACA

HR

p

PFS

5.1 mo

2.2 mo

0.43 (0.34-0.56)

<0.001

ORR

40%

13.9%

4.06 <0.001

CR

7.6%

1.0%

—

DoR

NR

6.0 mo

—

(all grades, %)

NIVO

DACA

p

Fatigue

19.9

14.6 NA

Pruritus

17

5.4 NA

Nausea

16.5

41.5 NA

Diarrhea

16

15.6 NA

Rash

15

2.9 NA

Vitiligo

10.7

0.5 NA

AE leading to discontinuation

6.8

11.7 NA

Pyrexia

7.3

4.9 NA

Hypothyroidism

4.4

0.5 NA

Hyperthyroidism

3.4

0 NA

Constipation

10.7

12.2 NA

Vomiting

6.3

21.0 NA

Neutropenia

0

11.2 NA

Thrombocytopenia

0

10.2 NA

Inclusion
Exclusion

- Men and women ≥18 years of age - Eastern Cooperative Oncology Group Performance Status of 0 or 1 - Untreated and histologically confirmed unresectable Stage III or Stage IV melanoma, as per the staging system of the American Joint Committee on Cancer - Measurable disease as per Response Evaluation Criteria in Solid Tumors 1.1 - Tumor tissue from an unresectable or metastatic site of disease must be provided for biomarker analyses - Known BRAF wild-type, as per regionally acceptable V600 mutational status testing. BRAF mutant patients and those with indeterminate or unknown BRAF status are not permitted to randomize

- Active brain metastases or leptomeningeal metastases - Ocular melanoma - Any active, known, or suspected autoimmune disease

Characteristics

NIVO

DACA

Age & sex

Median agedc-comma yr (range)

64 (18 - 86)

66 (26 - 87)

Maledc-comma no.

121 (57.6%)

125 (60.1%)

Femaledc-comma no.

89 (42.4%)

83 (39.9%)

—

ECOG PS

0 148 (70.5%)

121 (58.2%)

1 60 (28.6%)

84 (40.4%)

2 1 (0.5%)

3 (1.4%)

—

Metastasis stage

M1c

128 (61.0%)

127 (61.1%)

M0dc-comma M1adc-comma or M1b

82 (39.0%)

81 (38.9%)

—

Lactate dehydrogenase

≤ULN

120 (57.1%)

125 (60.1%)

>ULN

79 (37.6%)

74 (35.6%)

≤2xULN

178 (84.8%)

177 (85.1%)

>2xULN

21 (10.0%)

22 (10.6%)

History of brain metastases

Yes

7 (3.3%)

8 (3.8%)

No

203 (96.7%)

200 (96.2%)

—

PD-L1 status (min. 5%)

Positive

74 (35.2%)

74 (35.6%)

Negative or indeterminate

136 (64.8%)

134 (64.4%)

—

BRAF status

Mutation

0.0

0.0 No mutation

202 (96.2%)

204 (98.1%)

Not reported

8 (3.8%)

4 (1.9%)

—

Prior systemic therapy

Adjuvant therapy

32 (15.2%)

36 (17.3%)

Neoadjuvant therapy

1 (0.5%)

—

Geographic region

Europe or Canada

145 (69.0%)

145 (69.7%)

Israeldc-comma Australiadc-comma or South America

65 (31.0%)

63 (30.3%)

—

Ad-hoc:

no.pts inv.

no.pts comp.

NIVO

DACA

HR

p

—

OS (@1yr)
—

analisys of OS (@1yr)

NIVO

DACA

HR (95% CI)

PD-L1 status

positive

NR

12.39 0.30 (0.15-0.60)

negative or indeterminate

NR

10.22 0.48 (0.32-0.71)

M stage at study entry

M0/M1a/M1b

NR

12.39 0.31 (0.16-0.63)

M1c

NR

9.33 0.47 (0.32-0.71)

Age

< 65 yr

NR

11.17 0.52 (0.32-0.85)

≥ 65 and < 75 yr

NR

11.7 0.44 (0.24-0.81)

Gender

Male

NR

9.2 0.34 (0.22-0.54)

Female

NR

12.39 0.56 (0.33-0.95)

ECOG at entry

0 NR

11.83 0.32 (0.20-0.53)

1

12.68

7.43 0.64 (0.40-1.04)

LDH baeline

≤ ULN

NR

14.85 0.35 (0.19-0.62)

> ULN

NR

6.31 0.41 (0.26-0.65)

Region

W. Europe & Canada

NR

9.92 0.36 (0.23-0.56)

Rest of World

NR

11.17 0.53 (0.30-0.93)

History of brain metastases

Yes

NR

NE

No

NR

10.41 0.41 (0.29-0.58)

—

analisys of —

NIVO

DACA

HR (95% CI)

—

Melanoma: CheckMate 066 trial

EMA SPC links

2015-01-22

Caroline Robert

Nivolumab in Previously Untreated Melanoma without BRAF Mutation

Investigated (inv)

Comparator (comp)

Randomisation:

Primary tumour:

Subtype (biomarker):

Stage:

Line of therapy:

Primary

NIVO

DACA

HR

p

OS (@1yr)

72.9 %

42.1%

0.42 (0.25-0.73)

<0.001

—

—

—

—

—

Secondaries

NIVO

DACA

HR

p

PFS

5.1 mo

2.2 mo

0.43 (0.34-0.56)

<0.001

ORR

40%

13.9%

4.06

<0.001

CR

7.6%

1.0%

—

—

DoR

NR

6.0 mo

—

—

(all grades, %)

NIVO

DACA

p

Fatigue

19.9

14.6

NA

Pruritus

17

5.4

NA

Nausea

16.5

41.5

NA

Diarrhea

16

15.6

NA

Rash

15

2.9

NA

Vitiligo

10.7

0.5

NA