Abstract A026: Single Arm Pilot Study of Tumor Treating Fields (TTFields) with Nivolumab and Ipilimumab (IpiNivo) in Patients with Metastatic Uveal Melanoma (mUM)

Abstract TTFields have current FDA approval in GBM, NSCLC, and MPM that is refractory to frontline therapies. TTFields have also been shown to induce immunogenic cell death in vitro. Given the limited benefit of IpiNivo in mUM, we performed a signal seeking study of TTFields with IpiNivo in patients with refractory mUM. Patients with liver predominant mUM were treated with standard Ipi3Nivo1 dosing. After the first infusion, TTField arrays were placed for direct hepatic treatment with 200kHZ of alternating electric fields using the NovoTTF-200(O) device (/= 18 hours daily); with imaging every 12 weeks for efficacy assessment. Fresh tissue and blood samples were collected for correlative work. 10 patients were enrolled. Patients were predominately Male (60%) with an ECOG of 0 (70%) and a median age of 60 and LDH of 575. The average number of prior lines of therapy was 1.5 with 70% of patients having prior checkpoint inhibitors (50% prior IpiNivo). Treatment was tolerated well with expected toxicity from IpiNivo. Rash due to TTFields was seen in 50% of patients with maximum severity of grade 2. A single partial response (10% ORR) was noted in one patient who had 5 prior lines of therapy, including IpiNivo without prior benefit. Four of five patients evaluable for ctDNA had at least a 0.5 log reduction with treatment, with one patient having full clearance of ctDNA. Median PFS and OS were 2.0 and 10 months for all patients. A PFS of 21 months was seen in one patient, who had previously progressed on two prior lines of therapy including immune checkpoint inhibitor and elected to come off study treatment after 1 cycle due to side effects from IpiNivo. Higher baseline peripheral interferon gamma levels were seen in patients who had PR or SD on imaging, while higher osteopontin levels were seen in patients who had PD. Following treatment, increases in macrophage and T-cell proportions were seen in two of the three patients with paired biopsy samples. Longer PFS was also seen in these patients. Additionally, increase in metabolic enzyme expression for mitochondrial metabolism and a corresponding decrease in glycolytic enzyme expression in macrophages and T-cells was seen after treatment. Overall, signs of clinical benefit from TTFields with IpiNivo were seen in this refractory and high disease burden patient population without signs of unexpected toxicity. Spatial transcriptomic data will be presented in the full presentation. Citation Format: Justin C. Moser, Joseph Lownik, Michael Gordon, Daniel Mocan, Chase Venable, Villamejor Anton, Ying Li, Sunil Sharma, Alexis Larsen, Justin Moyers, Omid Hamid, Akil Merchant, Inderjit Mehmi. Single Arm Pilot Study of Tumor Treating Fields (TTFields) with Nivolumab and Ipilimumab (IpiNivo) in Patients with Metastatic Uveal Melanoma (mUM) abstract. In: Proceedings of the AACR Immuno-Oncology Conference (AACR IO): Discovery and Innovation in Cancer Immunology: Revolutionizing Treatment through Immunotherapy; 2026 Feb 18-21; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Immunol Res 2026;14(2 Suppl):Abstract nr A026.