Nivolumab in combination with RP1 (vusolimogene oderparepvec), a herpes simplex virus type 1–based oncolytic immunotherapy, showed activity in patients with advanced melanoma who experienced disease progression on standard anti‒PD-1‒based immunotherapy, according to findings from the phase I/II IGNYTE trial published in the Journal of Clinical Oncology.
“This study provides evidence that the combination of intratumoral RP1 and intravenous nivolumab is effective in patients with advanced melanoma when the disease was resistant to initial treatment with conventional immunotherapy,” stated lead study author Michael Wong, MD, PhD, FRCPC, Physician-in-Chief and Professor of Oncology, Department of Medicine, Roswell Park Comprehensive Cancer Center. “The treatment is well tolerated, and there is a very low incidence of significant side effects.”
Study Methods
One hundred and forty patients with unresectable stage IIIB–IV cutaneous melanoma and confirmed progression on a prior anti‒PD-1‒containing regimen were enrolled in the trial. Patients must have received at least 8 weeks of treatment with a PD-1 immune checkpoint inhibitor either as monotherapy or as part of a combination regimen as their most recent therapy.
All patients received an initial intratumoral dose of 1 x 106 plaque-forming units (PFU)/mL of RP1 followed by up to seven additional doses of RP1 at 1 x 107 PFU/mL every 2 weeks. Intravenous nivolumab was administered at 240 mg once every 2 weeks, which began with the second dose of RP1 for up to eight cycles followed by up to 21 additional cycles at a dose of 480 mg once every 4 weeks.
Key Study Findings
The confirmed objective response rate was 32.9% (95% confidence interval [CI] = 25.2%‒41.3%), including a complete response rate of 15%. Responses were observed with similar frequency, depth, duration, and kinetics in both injected and noninjected lesions—even including visceral lesions. The median duration of response was 33.7 months (95% CI = 14.1 to not reached). Deep and durable responses were even seen in patients with poor prognostic factors. At 1 year, the overall survival rate was 75.3% (95% CI = 66.9%‒81.9%; at 2 years, it was 63.3% (95% CI = 53.6%‒71.5%).
Biomarker analysis showed broad immune activation, including increased CD8+ T-cell infiltration and PD-L1 expression, that was associated with response.
The rates of treatment-related adverse events were 77.1% for grade 1 or 2 events, 9.3% for grade 3 events, and 3.6% for grade 4 events; no grade 5 events were reported.
Although the combination regimen needs to be studied further in randomized trials, if it continues to show significant activity, it could become a new standard approach for patients with melanoma who fail standard immunotherapy, according to the study authors.
Disclosure: The study was funded by Replimune Group Inc. For full disclosures of the study authors, visit ascopubs.org.
