What question did this study set out to answer?

This analysis aims to evaluate the immune and clinical responses following RP1 treatment in melanoma patients with bone metastases.

April 23, 2026Open Access

Bone metastases in melanoma: a real-world clinical and radiological descriptive analysis

Key Points

This analysis aims to evaluate the immune and clinical responses following RP1 treatment in melanoma patients with bone metastases.
Analyzed data from an ongoing clinical trial with advanced melanoma patients who previously failed anti-PD-1 therapy.
Conducted biomarker analyses using tumor biopsies and blood samples to assess immune responses and gene expression.
Performed RNA sequencing and immunohistochemistry to analyze the tumor microenvironment and T-cell functionality.
Observed an overall response rate (ORR) of 33.6%, with increased CD8 and PD-L1 expression in biopsies from many patients.
Identified upregulated genes linked to T-cell activation and cytotoxicity, indicating a more active tumor environment.
Noted systemic anti-tumor immunity with the expansion of specific T cells in blood, primarily in responding patients.

Abstract

Background: RP1 (vusolimogene oderparepvec) is a herpes simplex virus type 1 (HSV-1)-based oncolytic immunotherapy expressing GM-CSF and a fusogenic glycoprotein (GALV-GP-R-) 1.The primary analysis from the IGNYTE trial (data cutoff: March 8, 2024) showed an objective response rate (ORR) of 32.9% (15.0%complete response CR) in patients with anti-PD-1-failed melanoma treated with RP1 plus nivolumab by blinded independent central review using RECIST 1.1; median duration of response (DOR) was 33.7 months 2.Here we present pharmacodynamic data from paired tumor biopsies and blood samples supporting a follow-up efficacy analysis with a data cutoff of October 15, 2024.Methods: Patients with advanced melanoma and confirmed disease progression during 8 weeks of anti-PD-1 anti-CTLA-4 as the last prior treatment were enrolled (N = 140; NCT03767348) 2.For biomarker analysis, tumor biopsies were taken from the same lesion pretreatment and 43 days after the first RP1 dose.The tumor microenvironment was analyzed by immunohistochemistry (CD8 n = 46, PD-L1 n = 45) and multiplex immunofluorescence.RNA sequencing (NovaSeq 6000) was performed on pre-and post-treatment biopsies from 19 patients, with same-lesion biopsies available from 9 non-responders and 10 responders.Correlation analyses assessed baseline vs on-treatment gene expression and baseline tumor mutation burden (TMB) by clinical response.The CDR3 regions of TCR chains were sequenced from peripheral blood mononuclear cell DNA using the ImmunoSEQ assay.Results: By the data cutoff, 1 additional response had been documented as compared to the primary analysis, giving an ORR of 33.6% (16.4% CR) and median DOR (95% confidence interval) of 24.8 (14.1-not reached) months.Increased CD8 and PD-L1 expression was observed in paired biopsies from 17/46 (37%) and 25/45 (56%) patients, respectively.RNA sequencing demonstrated increased T-cell functionality, with upregulation of genes linked to activation, cytotoxicity (GZMA, TNF, IFNG, PRF1), IFN- signaling, and antigen presentation, confirming conversion to a more immunologically active tumor microenvironment.Increased PD-L1CD68 macrophages and PD-1CD8 T cells were also observed.Systemic anti-tumor immunity was evidenced by the expansion of tumor-and HSV-1-specific T cells in blood.These pharmacodynamic changes occurred predominantly in responders, including patients with no response to prolonged use of prior ipilimumab/nivolumab.No correlation was seen between TMB and clinical response.Conclusions: Biomarker data demonstrated increased expression of a range of genes known to be associated with responsiveness to anti-PD-1 therapy, which is consistent with and provides a mechanistic basis for the observed clinical responses to RP1 plus nivolumab after prior anti-PD-1 failure.

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