Abstract
611 RP1 plus nivolumab in patients with and without prior BRAF-directed therapy: a subgroup analysis of patients with anti-PD-1-failed BRAF-mutant melanoma from the IGNYTE clinical trial
Journal for immunotherapy of cancer, Vol.13(Suppl 2), pp.A696-A696
11/01/2025
DOI: 10.1136/jitc-2025-SITC2025.0611
Abstract
BackgroundApproximately 50% of melanomas have BRAF mutations, which drive the proliferation and survival of tumor cells via constitutive activation of the MAPK pathway. BRAF inhibitors (BRAFi) ± MEK inhibitors (MEKi) may be used to treat advanced BRAF V600-mutant melanoma as first-line therapy or after progression on anti-PD-1 therapy. However, prior treatment with BRAF-directed therapy can diminish the efficacy of subsequent treatment with anti-PD-1 therapy. Vusolimogene oderparepvec (RP1; an HSV-1-based oncolytic immunotherapy) combined with nivolumab demonstrated clinically meaningful, durable antitumor activity (objective response rate [ORR], 32.9% by RECIST 1.1; median duration of response [DOR], 33.7 months) in patients with melanoma and confirmed progression on prior anti-PD-1 therapy. Here we report the impact of prior BRAFi/MEKi therapy on the efficacy of RP1 plus nivolumab.MethodsPatients with melanoma and confirmed progression on anti-PD-1 ± anti-CTLA-4 therapy for ≥8 weeks as the last prior treatment were enrolled. Prior treatment with BRAFi ± MEKi therapy was allowed for BRAF V600 mutation-positive melanoma. RP1 was given intratumorally at 1×106 PFU/mL initially, then at 1×107 PFU/mL Q2W (≤7 doses) with intravenous nivolumab (240 mg), followed by nivolumab alone (240 mg Q2W or 480 mg Q4W) for up to 2 years. This post hoc analysis evaluated ORR, DOR, and progression-free survival (PFS) by RECIST 1.1 per independent review, and overall survival (OS) in patients with BRAF-mutant melanoma, stratified by prior BRAFi treatment (data cutoff: March 8, 2024).ResultsOf 140 enrolled patients, 53 had BRAF-mutant melanoma, including 16 (30.2%) who had received BRAFi/MEKi prior to anti-PD-1 therapy (BRAFi-exposed) and 37 (69.8%) who were BRAFi-naïve. The confirmed ORR was 12.5% in the BRAFi-exposed group vs 43.2% in the BRAFi-naïve group (table 1). Median DOR was 3.9 months in the BRAFi-exposed group vs 33.7 months in the BRAFi-naïve group. Median PFS was 1.9 months in the BRAFi-exposed group vs 5.6 months in the BRAFi-naïve group; the 12-month PFS rate was 13.3% vs 40.4%, respectively. The 12-month OS was 71.4% in BRAFi-exposed patients and 85.9% in BRAFi-naïve patients. Fifteen of the 37 BRAFi-naïve patients were subsequently treated with BRAFi ± MEKi for a median of 13.9 months with an ORR of 66.7%.ConclusionsIn patients with advanced BRAF-mutant melanoma that progressed on prior anti-PD-1 therapy, RP1 plus nivolumab appeared to be more effective in BRAFi-naïve patients. This finding is consistent with literature showing that BRAF-directed therapy leads to cross-resistance to subsequent immunotherapy.Trial RegistrationClinicalTrials.gov NCT03767348Ethics ApprovalThe study was conducted in accordance with the ethical principles originating from the Declaration of Helsinki and was approved by the institutional review board/ethics committee at each participating site. Written informed consent was obtained from all patients prior to the conduct of any study-related procedures.Abstract 611 Table 1Efficacy by prior BRAFi/MEKi treatmentCR, complete response; NR, not reached; PD, progressive disease; PR, partial response; SD, stable disease.
Details
- Title: Subtitle
- 611 RP1 plus nivolumab in patients with and without prior BRAF-directed therapy: a subgroup analysis of patients with anti-PD-1-failed BRAF-mutant melanoma from the IGNYTE clinical trial
- Creators
- Katy Tsai - University of California, San FranciscoBartosz ChmielowskiJoseph Sacco - Clatterbridge Cancer Centre NHS Foundation TrustCaroline Robert - Institut Gustave RoussyJudith Michels - Institut Gustave RoussyGino K InEva CouseloDirk SchadendorfGeorgia Beasley - Duke UniversityJiaxin NiuAri VanderWalde - West Cancer CenterTrisha Wise-Draper - University of CincinnatiMohammed Milhem - University of IowaTawnya Bowles - Intermountain Medical CenterCéleste LebbéCaroline Gaudy-MarquesteJunhong ZhuChris TucciMarcus VianaJeannie HouMichael Wong - Roswell Park Comprehensive Cancer Center
- Resource Type
- Abstract
- Publication Details
- Journal for immunotherapy of cancer, Vol.13(Suppl 2), pp.A696-A696
- DOI
- 10.1136/jitc-2025-SITC2025.0611
- eISSN
- 2051-1426
- Publisher
- BMJ Publishing Group LTD
- Language
- English
- Date published
- 11/01/2025
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9985024248902771
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