Melanoma: RELATIVITY-047 trial

Abbreviations

No EU-CTR

Investigated (inv)
Comparator (comp)

RELA+NIVO

NIVO

355

359

Phase:

3

Randomisation:

Double blind

Primary tumour:

Melanoma

Subtype (biomarker):

Any

Stage:

meta

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)