Abstract CT282: Immune checkpoint inhibitors plus personal dendritic cell vaccines in patients with metastatic melanoma

Abstract Metastatic melanoma patients treated with monoclonal antibody immune checkpoint inhibitors (ICI) have a response rate of 35% to 50% and a 5-year overall survival (OS) of about 50%. Personal DC-ATA vaccines are a promising investigational immunotherapy consisting of autologous dendritic cells (DCs) loaded ex vivo with autologous tumor antigens (ATA) from self-renewing autologous cancer cells. In metastatic melanoma clinical trials conducted in the pre-ICI era, DC-ATA was associated with increased 5-year OS compared to historical and contemporary randomized patients. NCT03743298 is a phase IB trial testing the combination of ICI + DC-ATA. Eligible patients have advanced melanoma, at least one resectable lesion, and a treatment plan that includes an anti-programmed death molecule (PD-1) regimen that does not include an anti-CTLA-4 antibody. A cell suspension from fresh resected metastatic melanoma tissue is incubated in liquid media containing growth factors that favor stem cells and progenitor cell proliferation. A lysate of irradiated tumor cells (ITC) from the short-term cell line serves as ATA. Patients’ peripheral blood mononuclear cells are enriched for monocytes that are differentiated into DC by culturing with interleukin-4 and granulocyte-macrophage colony-stimulating-factor. DC and ATA lysate are co-incubated for antigen loading. During the 8-9 weeks while DC-ATA is being manufactured, patients receive standard ICI-based therapy, then DC-ATA is injected s.c. for six months at weeks 1, 2, 3, 8, 12, 16, 20, and 24 concurrently with ICI-based treatment. Patients are monitored for adverse events (AEs); objective tumor response is determined in patients with measurable disease. 8 patients have completed treatment: 3 males, 5 females, mean age 75 years (62 to 89 years). At the time of enrollment, clinical stages were stage 3 regional recurrence (n=2), M1A (n=1), M1B (n=2), and M1C (n=3). Before starting concurrent DC-ATA, 3 patients received the anti-PD-1 pembrolizumab, 4 received opdualag (anti-PD-1 nivolumab + anti-LAG3 relatlimab), and 1 received pembrolizumab followed by opdualag. 61 of 64 possible DC-ATA doses were injected. One patient discontinued DC-ATA because of persistent rash and pruritus that began during pembrolizumab. All patients experienced local injection site reactions. No patient experienced grade 3 or 4 AEs; the highest-grade AEs experienced were 1 or 2 (both n=4). All patients experienced local injection site reactions. The RECIST response rate for the 6 patients with measurable disease is 100% (54% to 100% 95% CI), 2 complete and 4 partial. OS from enrollment is 56+, 36+, 30+, 19+, 17+, 14+, 14, and 11+ months. DC-ATA can be safely administered concurrently with ICI without increased toxicity and may increase efficacy over what might be expected with ICI alone. Additional testing of sequential/concurrent ICI + DC-ATA combination immunotherapy is warranted. Citation Format: Chaitali S. Nangia, Katrina L. Lopez, Gabriel I. Nistor, Robert O. Dillman. Immune checkpoint inhibitors plus personal dendritic cell vaccines in patients with metastatic melanoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(8_Suppl):Abstract nr CT282.