Nivolumab/Relatlimab Elicit IC Activity in Anti–PD-L1–Refractory Melanoma Brain Mets

The median overall survival (OS) in patients with BICR-confirmed melanoma brain metastases who received nivolumab plus relatlimab was 21.5 months.

Nivolumab (Opdivo) plus relatlimab demonstrated intracranial activity in patients with anti–PD-(L)1 refractory melanoma who have melanoma brain metastases, though more data is needed to confirm efficacy, according to a presentation on the phase 1/2a RELATIVITY-020 trial (NCT01968109) shared at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting.¹

The clinical benefit rate was 63.0% (n = 17/27), with 3.7% of patients achieving a complete response and 18.5% achieving a partial response. The median time to intracranial response was 3.2 months (95% CI, 1.7-53.4), and the median duration of intracranial response was not reached (NR; 95% CI, 4.6-NR). Further, the overall response rate (ORR) was 22.2% (95% CI, 8.6%-42.3%); 40.7% of patients had stable disease, 18.5% had progressive disease, and 18.5% were unable to be determined.

Of the 17 patients with blinded independent central review (BICR)-confirmed central nervous system (CNS) lesions, 14 patients had baseline lesions and at least 1 on-treatment BICR brain tumor assessment up to progression or the start of subsequent chemotherapy. The median best reduction from baseline was –19.5% (range, –72% to 44%); 8 patients tumor burden demonstrated a sustained decrease.

The median intracranial progression-free survival (PFS) was NR (95% CI, 5.55-NR), and 63.3% of patients were free of intracranial progression for 1 year or more.

The median overall survival (OS) in patients with BICR-confirmed melanoma brain metastases was 21.5 months (95% CI, 10.9-29.4); the 12-month OS rate was 69.7%, the 24-month OS rate was 42.6%, and the 36-month OS rate was 27.1%.

“[Nivolumab plus relatlimab] demonstrates intracranial activity in an anti–PD-(L)1–refractory population; however, the retrospective nature of these data and sample size limitations warrant further prospective studies to confirm the effectiveness of [nivolumab plus relatlimab],” wrote lead study author Hussein A. Tawbi, MD, PhD, professor, deputy chair, and director of Personalized Cancer Therapy, in the Department of Melanoma Medical Oncology, Division of Cancer Medicine, at the University of Texas MD Anderson Cancer Center, in the presentation.¹

This post-hoc analysis identified a total of 39 patients from parts C, D, and E of the RELATIVITY-020 trial who had suspected intracranial lesions; of those patients, 27 had BICR-confirmed intracranial lesions and were included in the analysis. Also, 17 patients had at least 1 target intracranial lesion at baseline, and 14 patients had both a baseline lesion and at least 1 on-treatment brain scan.

Patients were eligible for the RELATIVITY-020 trial if they had histologic or cytologic confirmation of incurable metastatic and/or unresectable solid malignancy; those with treated brain metastases and no radiological evidence of progression for at least 4 weeks after treatment were also included.

The median age of patients was 63 years (range, 35-81), 59.3% were male, 59.3% had an ECOG performance status of 0, 100% had stage IV disease at entry, and 70.4% had BRAF status wild-type. Additionally, 51.9% did not have liver metastasis, 66.7% had a cutaneous melanoma subtype, 44.4% had PD-L1 status of less than 1%, and 51.9% had 1 intracranial target lesion. The median sum of target lesions at baseline was 18.0 mm (range, 10-54).

The median number of prior systemic therapies was 2 (range, 1-10); 92.6% of patients underwent prior surgery, 96.3% had prior radiotherapy, and 100% received prior immunotherapy. The time between radiotherapy and the first study dose was 3 or more months in 48.1% of patients.

This study’s objective was to evaluate the intracranial activity, through baseline and on-study scans, of nivolumab plus relatlimab in patients with melanoma brain metastases who progressed on prior anti–PD-(L)1 therapy in the RELATIVTY-020 trial.

Study investigators noted that prior results from part D of the RELATIVITY-020 trial showed an ORR of 12% in a cohort of patients with PD-(L)1–refractory melanoma who were treated with the study combination.²

References

1. Tawbi HA, Hodi SF, Lipson EJ, et al. RELATIVITY-020: intracranial activity of nivolumab + relatlimab in patients with anti-PD-(L)1 refractory melanoma with melanoma brain metastases. J Clin Oncol. 2025;43(suppl 16):9525. Doi:10.1200/JCO.2025.43.16_suppl.9525
2. Ascierto PA, Lipson EJ, Dummer R, et al. Nivolumab and relatlimab in patients with advanced melanoma that had progressed on anti-programmed death-1/programmed death ligand 1 therapy: results from the phase I/IIa RELATIVITY-020 trial. J Clin Oncol. 2023;41(15):2724-2735. doi:10.1200/JCO.22.02072