Details of data from Melanoma clinical trials

Investigated (inv)

Comparator (comp)

RELA+NIVO

NIVO

355

359

Phase:

3

Randomisation:

Double blind

Primary tumour:

Melanoma

Subtype (biomarker):

Any

Stage:

Line of therapy:

L1

Primary

RELA+NIVO

NIVO

HR

p

PFS

10.12 mo

4.63 mo

0.75 (0.62-0.92)

0.006 PFS @1yr

47.7%

36.0%

—

Secondaries

RELA+NIVO

NIVO

HR

p

OS @1yr

77.0%

71.6%

—

OS @2yr

63.7%

58.3%

—

OS

NR

34.1 mo.

0.80 (0.6–1.0)

0.0593

—

(all grades, %)

RELA+NIVO

NIVO

p

Any AE gr.3-4

40.3

33.4 NA

Treatment-related AE (gr.3-4)

18.9

9.7 NA

AE leading to discontinuation of treatment (gr.3-4)

8.5

3.1 NA

Pruritus

23.4

15.9 NA

Fatigue

23.1

12.8 NA

Rash

15.5

12.0 NA

Diarrhea

13.5

9.2 NA

Hypothyroidism or thyroiditis

18.0

13.9 NA

Hyperthyroidism

6.2

6.7 NA

Hepatitis

5.6

2.5 NA

Adrenal insufficiency

4.2

0.8 NA

Hypophysitis

2.5

0.8 NA

Nephritis and renal dysfunction

2.0

1.4 NA

Hypersensitivity

1.1

1.1 NA

Inclusion
Exclusion

- Participants must have histologically confirmed Stage III (unresectable) or Stage IV melanoma, per the AJCC staging system - Participants must not have had prior systemic anticancer therapy for unresectable or metastatic melanoma - Tumor tissue from an unresectable or metastatic site of disease must be provided for biomarker analyses Other protocol defined inclusion/exclusion criteria could apply

- Participants must not have active brain metastases or leptomeningeal metastases - Participants must not have uveal melanoma - Participants must not have an active, known, or suspected autoimmune disease Other protocol defined inclusion/exclusion criteria could apply

Characteristics

RELA+NIVO

NIVO

Agedc-comma sex

Median age (range) yr

63.0 (20–94)

62.0 (21–90)

Female - no.(%)

145 (40.8)

153 (42.6)

—

Previous systemic therapy - no.(%)

Adjuvant

31 (8.7)

26 (7.2)

Neoadjuvant

2 (0.6)

1 (0.3)

Unknown or other

0 2 (0.6)

—

Metastasis stage - no.(%)

M0

35 (9.9)

23 (6.4)

M1a or b

162 (45.6)

195 (54.3)

M1c

151 (42.5)

127 (35.4)

M1d

6 (1.7)

11 (3.1)

Melanoma subtype classification - no.(%)

Cutaneous acral

41 (11.5)

41 (11.4)

Cutaneous nonacral

249 (70.1)

254 (70.8)

Mucosal

23 (6.5)

28 (7.8)

Other

42 (11.8)

36 (10.0)

ECOG PS - no.(%)

0 236 (66.5)

242 (67.4)

1 119 (33.5)

117 (32.6)

—

LDH level - no.(%)

>ULN

130 (36.6)

128 (35.7)

>2x ULN

32 (9.0)

31 (8.6)

—

Sites with ≥1 lesion - no.(%)

1 127 (35.8)

158 (44.0)

2 111 (31.3)

102 (28.4)

≥3

112 (31.5)

87 (24.2)

—

LAG-3 expression - no.(%)

≥1%

268 (75.5)

269 (74.9)

<1%

87 (24.5)

90 (25.1)

—

PD-L1 expression - no.(%)

≥1%

146 (41.1)

147 (40.9)

<1%

209 (58.9)

212 (59.1)

≥5%

88 (24.8)

86 (23.9)

<5%

267 (75.2)

273 (76.0)

BRAF status - no.(%)

BRAF MTdc-plus

136 (38.3)

139 (38.7)

BRAF MT-

219 (61.7)

220 (61.3)

—

Metastasis stage with LDH level - no.(%)

M0dc-comma M1 and normal LDH level

232 (65.4)

237 (66.0)

M1 and elevated LDH level

123 (34.6)

122 (34.0)

—

Other

Median tumor burden (range) - mm

59.0 (10–317)

54.5 (10–548)

—

Ad-hoc:

no.pts inv.

no.pts comp.

RELA+NIVO

NIVO

HR

p

PFS (LAG-3 ≥1%)

268

269 12.58 mo.

4.76 mo.

0.75 (0.59–0.95)

—

PFS (LAG-3 <1%)

87

90 4.83 mo.

2.79 mo.

0.78 (0.54–1.15)

—

PFS
PFS @1yr

analisys of PFS

RELA+NIVO

NIVO

HR (95% CI)

LAG-3

≥1%

—

0.75 (0.59–0.95)

<1%

—

0.78 (0.54–1.15)

PD-L1

≥1%

—

0.95 (0.68–1.33)

<1% or nonquantifiable

—

0.66 (0.51–0.84)

PD-L1

≥5%

—

0.86 (0.54–1.38)

<5% or nonquantifiable

—

0.73 (0.58–0.90)

Metastasis stage

M0dc-comma M1 and normal LDH level

—

0.71 (0.55–0.92)

M1 and elevated LDH level

—

0.79 (0.58–1.09)

BRAF status

Mutant

—

0.74 (0.54–1.03)

Wild type

—

0.76 (0.59–0.98)

LDH

≤ULN

—

0.70 (0.54–0.91)

>ULN

—

0.80 (0.59–1.09)

LDH

≤2x ULN

—

0.75 (0.60–0.92)

>2x ULN

—

0.75 (0.42–1.35)

Age

<65 yr

—

0.83 (0.64–1.09)

≥65 yr

—

0.69 (0.51–0.93)

Sex

Male

—

0.68 (0.52–0.89)

Female

—

0.88 (0.65–1.19)

ECOG

0 —

—

0.74 (0.57–0.95)

1 —

—

0.78 (0.56–1.07)

analisys of PFS @1yr

RELA+NIVO

NIVO

HR (95% CI)

—

Melanoma: RELATIVITY-047 trial

EMA SPC links

2022-01-06

Hussein A. Tawbi

Relatlimab and Nivolumab versus Nivolumab in Untreated Advanced Melanoma

Investigated (inv)

Comparator (comp)

Randomisation:

Primary tumour:

Subtype (biomarker):

Stage:

Line of therapy:

Primary

RELA+NIVO

NIVO

HR

p

PFS

10.12 mo

4.63 mo

0.75 (0.62-0.92)

0.006

PFS @1yr

47.7%

36.0%

—

—

Secondaries

RELA+NIVO

NIVO

HR

p

OS @1yr

77.0%

71.6%

—

—

OS @2yr

63.7%

58.3%

—

—

OS

NR

34.1 mo.

0.80 (0.6–1.0)

0.0593

—

—

—

—

—

(all grades, %)

RELA+NIVO

NIVO

p

Any AE gr.3-4

40.3

33.4

NA

Treatment-related AE (gr.3-4)

18.9

9.7

NA

AE leading to discontinuation of treatment (gr.3-4)

8.5

3.1

NA

Pruritus

23.4

15.9

NA

Fatigue

23.1

12.8

NA

Rash

15.5

12.0

NA