A phase I/II clinical study of DOC1021 (dubodencel) dendritic cell immunotherapy for refractory melanoma.

TPS9602 Background: DOC1021 is an autologous dendritic cell (DC)-based immunotherapy. Loading of DC in tandem with both patient autologous tumor protein and amplified mRNA induces p38MAPK and mTORC1 signaling cascades that initiate cDC1-like skewing of monocyte-derived DC, generating downstream development of highly cytolytic memory effectors. This approach targets the multitude of antigens in a patient’s own tumor, does not require myeloablative chemotherapy and has demonstrated a favorable safety profile in Phase I glioblastoma (NCT04552886) and pancreatic cancer trials (NCT04157127). Pre-clinical studies in a variety of animal models, including melanoma (subcutaneous B16F0-OVA tumors), have also shown improved tumor responses and evidence of antigen-specific immunity. While immune checkpoint inhibitors (ICI) have improved clinical outcomes in melanoma, many patients ultimately develop resistance, resulting in refractory disease. We hypothesize that DOC1021 may overcome ICI resistance in refractory melanoma through the generation of durable T cell responses with novel specificities, promoting long-term anti-tumor T cell surveillance and improved survival. Methods: This is a prospective, multi-center, open-label Phase I/II study in patients with refractory cutaneous melanoma, unresectable or metastatic, with progression following ≥1 prior systemic therapies including anti-PD-1. The study consists of two components: an initial Phase I study to confirm safety/tolerability of DOC1021 in refractory melanoma, and subsequently, a single-arm Phase II cohort to assess efficacy. Up to 12 patients will be enrolled in Phase I, and up to 35 evaluable patients will be enrolled in Phase II using a Simon’s optimal two-stage design. DOC1021 will be prepared from mobilized peripheral blood mononuclear cells (PBMC), loaded with autologous tumor lysate and amplified tumor mRNA. All patients will receive 2 courses of DOC1021 (12 x 10 6 cells per administration) 2 weeks apart via perinodal injections near active disease sites, plus peg-interferon (pIFN) adjuvant on the day of each DOC1021 administration and 1 week after for 4 total doses. An optional DOC1021 booster course may also be given approximately 6 months after the first DOC1021 administration. The primary endpoint of the Phase I study is dose-limiting toxicities of DOC1021, while the primary endpoint of the Phase II study is the overall response rate per RECIST 1.1 criteria. This study will also evaluate survival, tumor responses, changes in circulating tumor DNA, as well as further investigate DOC1021’s mechanism of action through biomarker-rich analyses of serial tumor biopsies and blood sampling. The first patient to enroll in the Phase I safety study is planned for early 2026. Clinical trial information: NCT07288112 .