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Nivolumab and Relatlimab in Patients With Advanced Melanoma That Had Progressed on Anti-Programmed Death-1/Programmed
Paolo Antonio Ascierto1, Evan J Lipson2, Reinhard Dummer3
1Melanoma, Cancer Immunotherapy, and Development Therapeutics Unit, Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale," Naples, Italy.
Purpose:
Nivolumab and relatlimab activity in advanced melanoma with prior progression on anti-programmed death-1/programmed death ligand 1 (PD-(L)1)-containing regimens is under investigation. RELATIVITY-047 demonstrated significantly improved progression-free survival (PFS) for nivolumab and relatlimab over nivolumab in previously untreated advanced melanoma.
Methods:
The phase I/IIa, open-label RELATIVITY-020 trial part D assessed efficacy and safety of nivolumab and relatlimab in advanced melanoma with progression during, or within 3 months of, 1 (D1) or ≥ 1 (D2) anti-PD-(L)1-containing regimens. Safety was a primary end point. Objective response rate (coprimary end point) and PFS by blinded independent central review (BICR) were assessed.
Results:
Five hundred eighteen patients (D1 = 354; D2 = 164) received nivolumab and relatlimab. Among evaluable patients, the objective response rate by BICR was 12.0% (95% CI, 8.8 to 15.8) in D1 (n = 351) and 9.2% (95% CI, 5.2 to 14.7) in D2 (n = 163). Responses appeared to be enriched among patients with tumors expressing programmed death ligand 1 or lymphocyte activation gene 3; however, responses were observed regardless of programmed death ligand 1 and lymphocyte activation gene 3 expression (1%). The median duration of response was not reached (95% CI, 12.9 to not reached) in D1 and 12.8 months (95% CI, 6.9 to 12.9) in D2. The median PFS by BICR was 2.1 months (95% CI, 1.9 to 3.5) in D1 and 3.2 months (95% CI, 1.9 to 3.6) in D2; the 6-month PFS rate was 29.1% (95% CI, 24.2 to 34.1) and 27.7% (95% CI, 20.5 to 35.4), respectively. The grade 3-4 treatment-related adverse event incidence was 15.0% in D1 and 12.8% in D2. One case of grade 3 myocarditis and no treatment-related deaths occurred across part D.
Conclusion:
Nivolumab and relatlimab had a manageable safety profile and demonstrated durable clinical activity in a proportion of patients with heavily pretreated advanced melanoma with prior progression on anti-PD-(L)1-containing regimens.
Abstract:
[Media: see text].
Insights
Nivolumab and relatlimab show manageable safety and durable activity in advanced melanoma patients who progressed on prior anti-PD-(L)1 therapy. This combination offers a new option for heavily pretreated patients.
Area of Science:
- Oncology
- Immunotherapy
- Melanoma Research
Background:
- Advanced melanoma remains a challenge, particularly after progression on anti-programmed death-1/programmed death ligand 1 (PD-(L)1) therapies.
- Investigating novel combinations is crucial for improving outcomes in heavily pretreated patients.
Purpose of the Study:
- To assess the efficacy and safety of nivolumab and relatlimab in advanced melanoma patients with prior progression on anti-PD-(L)1 regimens.
- To evaluate response rates and progression-free survival in this difficult-to-treat population.
Main Methods:
- Phase I/IIa, open-label RELATIVITY-020 trial, part D.
- Patients with advanced melanoma and progression on 1 (D1) or ≥1 (D2) anti-PD-(L)1 regimens received nivolumab and relatlimab.
- Efficacy (objective response rate, progression-free survival) and safety were assessed by blinded independent central review.
Main Results:
- Objective response rates were 12.0% (D1) and 9.2% (D2).
- Median progression-free survival was 2.1 months (D1) and 3.2 months (D2).
- Grade 3-4 treatment-related adverse events occurred in 15.0% (D1) and 12.8% (D2), with a manageable safety profile.
Conclusions:
- Nivolumab and relatlimab demonstrate durable clinical activity in a subset of heavily pretreated advanced melanoma patients.
- The combination offers a manageable safety profile and potential benefit for patients progressing on prior anti-PD-(L)1 therapies.
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