RELATIVITY-047: trial | Bending the Curve: Trial by Trial

RELATIVITY-047

A Study of Relatlimab Plus Nivolumab Versus Nivolumab Alone in Participants With Advanced Melanoma

Population

Previously untreated metastatic or unresectable melanoma

Design

Double-blind randomised phase 2/3 trial of a fixed-dose combination of relatlimab and nivolumab versus nivolumab alone, given intravenously every 4 weeks. Primary end point progression-free survival by blinded independent central review. Control was nivolumab alone; there was no nivolumab-plus-ipilimumab arm.

Primary endpoint

PFS

Arms

Relatlimab plus nivolumab (experimental, n = 355): Fixed-dose combination of relatlimab 160 mg plus nivolumab 480 mg intravenously every 4 weeks
Nivolumab (control, n = 359): Nivolumab 480 mg intravenously every 4 weeks

People

Tawbi HA, senior author Long GV

PFSHR 0.75 (95% CI 0.62–0.92)Δ median PFS+5.5 monthsΔ 12-month PFS+11.7 pointsOSHR 0.80 (95% CI 0.66–0.99)Δ median OS+16.9 monthsΔ ORR+10 points

Show the numbers

Results reported for RELATIVITY-047
Endpoint	Analysis	Relatlimab plus nivolumab	Nivolumab	Effect
PFSRandomised population as described in the abstract (analysis population not stated there)	primaryTawbi 2022	median 10.1 months (6.4–15.7); 47.7% at 12 mo (41.8–53.2%)	median 4.6 months (3.4–5.6); 36% at 12 mo (30.5–41.6%)	HR 0.75 (95% CI 0.62–0.92)P=0.006P value by the log-rank test. Grade 3 or 4 treatment-related adverse events: 18.9% with relatlimab plus nivolumab versus 9.7% with nivolumab.
OSRandomised patients, median follow-up 33.8 months, as described in the abstract	long term-updatemedian follow-up 33.8 monthsTawbi 2025	median 51 months	median 34.1 months (25.2–44.7)	HR 0.80 (95% CI 0.66–0.99)Descriptive update. The abstract recalls the overall survival improvement as clinically meaningful but not statistically significant and notes that the upper bound of the hazard-ratio interval is now below 1. The 95% confidence interval of the combination median is printed as 34.0 to not reached and is not recorded as a numeric interval.
ORRRandomised patients, median follow-up 33.8 months, as described in the abstract	long term-updatemedian follow-up 33.8 monthsTawbi 2025	43.7% (38.4–49.0%)	33.7% (28.8–38.9%)	Described in the abstract as a numerically higher objective response rate.
OSRandomised patients, minimum follow-up 45.3 months, as described in the abstract	long term-updateLipson 2025	52% at 4 y (46.6–57.1%)	42.8% at 4 y (37.5–47.9%)	Descriptive 4-year update; the abstract states overall survival was numerically better. Minimum follow-up 45.3 months.

Results reported for RELATIVITY-047
Endpoint	Analysis	Relatlimab plus nivolumab	Nivolumab	Effect
PFSRandomised population as described in the abstract (analysis population not stated there)	primaryTawbi 2022	median 10.1 months (6.4–15.7); 47.7% at 12 mo (41.8–53.2%)	median 4.6 months (3.4–5.6); 36% at 12 mo (30.5–41.6%)	HR 0.75 (95% CI 0.62–0.92)P=0.006P value by the log-rank test. Grade 3 or 4 treatment-related adverse events: 18.9% with relatlimab plus nivolumab versus 9.7% with nivolumab.
OSRandomised patients, median follow-up 33.8 months, as described in the abstract	long term-updatemedian follow-up 33.8 monthsTawbi 2025	median 51 months	median 34.1 months (25.2–44.7)	HR 0.80 (95% CI 0.66–0.99)Descriptive update. The abstract recalls the overall survival improvement as clinically meaningful but not statistically significant and notes that the upper bound of the hazard-ratio interval is now below 1. The 95% confidence interval of the combination median is printed as 34.0 to not reached and is not recorded as a numeric interval.
ORRRandomised patients, median follow-up 33.8 months, as described in the abstract	long term-updatemedian follow-up 33.8 monthsTawbi 2025	43.7% (38.4–49.0%)	33.7% (28.8–38.9%)	Described in the abstract as a numerically higher objective response rate.
OSRandomised patients, minimum follow-up 45.3 months, as described in the abstract	long term-updateLipson 2025	52% at 4 y (46.6–57.1%)	42.8% at 4 y (37.5–47.9%)	Descriptive 4-year update; the abstract states overall survival was numerically better. Minimum follow-up 45.3 months.

Hazard ratio (95% CI) by endpoint. Values below 1 favour the experimental arm.

Data table

Endpoint	HR	95% CI
PFS	0.75	0.62–0.92
OS	0.8	0.66–0.99

Illustrative — modelled from reported values, not trial data. PFS, primary.

Show curves

Relatlimab plus nivolumab (experimental)
Nivolumab (control)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)

Months	Relatlimab plus nivolumab	Nivolumab
0	100.0%	100.0%
6	66.2%	40.5%
13	41.0%	14.1%
19	27.1%	5.7%
25	18.0%	2.3%

Illustrative — modelled from reported values, not trial data. OS, long term-update.

Show curves

Relatlimab plus nivolumab (experimental)
Nivolumab (control)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)

Months	Relatlimab plus nivolumab	Nivolumab
0	100.0%	100.0%
32	64.7%	52.2%
64	41.9%	27.2%
96	27.1%	14.2%
128	17.6%	7.4%

Appears in

2022 Relatlimab plus nivolumab: RELATIVITY-047 and LAG-3 blockade (2022)

Sources

Tawbi HA, Schadendorf D, Lipson EJ, Ascierto PA, Matamala L, Castillo Gutiérrez E, et al. Relatlimab and Nivolumab versus Nivolumab in Untreated Advanced Melanoma. N Engl J Med. 2022;386(1):24-34.
PubMed DOI
Tawbi HA, Hodi FS, Lipson EJ, Schadendorf D, Ascierto PA, Matamala L, et al. Three-Year Overall Survival With Nivolumab Plus Relatlimab in Advanced Melanoma From RELATIVITY-047. J Clin Oncol. 2025;43(13):1546-1552.
PubMed DOI
Lipson EJ, Stephen Hodi F, Tawbi H, Schadendorf D, Ascierto PA, Matamala L, et al. Nivolumab plus relatlimab in advanced melanoma: RELATIVITY-047 4-year update. Eur J Cancer. 2025;225:115547.
PubMed DOI