Privately held Rockville, Maryland-based Immunomic Therapeutics, Inc. has initiated a first-in-human Phase I trial of ITI-5000, a self-amplifying RNA vaccine targeting two antigens selectively expressed in triple-negative breast cancer, in patients who have completed standard curative-intent therapy. The trial's adjuvant setting — enrolling women who have already finished surgery, chemotherapy, and radiation — reflects a strategic bet that vaccine-primed immunity may reduce relapse risk in a subtype where residual micrometastatic disease drives poor outcomes despite aggressive upfront treatment.
The two-part VITAL-TNBC study (NCT07652242) will enroll around 60 adults with histologically confirmed stage II–III TNBC within 36 months of definitive surgery. Part A will determine maximum tolerated dose, while Part B will see pembrolizumab (Keytruda) added to ITI-5000 at the selected dose. Exploratory endpoints include immune response measures and changes in circulating tumor DNA. The trial is currently recruiting at START Midwest in Grand Rapids, Michigan, with primary completion anticipated in February 2028.
ITI-5000 encodes a fusion construct linking two tumor-associated antigens — HERV-K, a human endogenous retroviral protein aberrantly re-expressed in TNBC, and CT83 (also known as KK-LC-1), a cancer-testis antigen reported among the most selectively expressed genes in the TNBC subtype — to LAMP-1, a lysosomal membrane protein that directs the expressed antigen into the endolysosomal compartment. This LAMP-1 trafficking signal, the core of Immunomic Therapeutics' UNITE platform originally licensed from Johns Hopkins University in 2006, enhances MHC class II antigen presentation and is intended to broaden the T cell response beyond what cytoplasmic antigen expression alone would generate. The saRNA backbone amplifies the antigen transcript intracellularly from microgram-range doses, a property that distinguishes the format from conventional mRNA vaccines and could reduce the dose burden needed to sustain immunogenicity. The combination with pembrolizumab in Part B is premised on the hypothesis that checkpoint blockade may prevent exhaustion of the vaccine-primed T cell population.