Immunomic Therapeutics, Inc. has opened a first-in-human Phase I study of ITI-5000, a self-amplifying RNA vaccine targeting two antigens expressed in triple-negative breast cancer, in patients who have completed standard curative-intent therapy. The trial's significance lies in its antigen selection: HERV-K, an endogenous retroviral protein with limited normal tissue expression, and CT83, a cancer-testis antigen, represent targets with a theoretical therapeutic window that conventional chemotherapy cannot exploit. Applying self-amplifying RNA technology to a tumor-associated antigen vaccine in the adjuvant TNBC setting is a design that has not previously reached human testing, according to the trial record.
The Phase I VITAL-TNBC study (NCT07652242) enrolls up to 60 female adults with histologically confirmed stage II–III TNBC who have completed surgery, chemotherapy, radiation, and, where applicable, pembrolizumab (Keytruda), within 36 months of definitive surgery. The two-part study opens with a modified 3+3 dose-escalation in Part A, testing ITI-5000 monotherapy at 1 µg and 10 µg administered intramuscularly every 28 days for three doses. Part B combines ITI-5000 at the identified maximum tolerated dose with pembrolizumab at standard FDA-approved dosing — either 200 mg intravenously every three weeks or 400 mg every six weeks — given every 21 days for three doses. Primary endpoints assess dose-limiting toxicities and overall safety and tolerability, with primary completion anticipated in February 2028.
ITI-5000 encodes a fusion construct of HERV-K and CT83 antigens linked to LAMP-1, a lysosomal targeting signal that routes antigen toward MHC class II presentation and is intended to amplify both CD4 and CD8 T-cell responses. The self-amplifying RNA backbone, delivered in lipid nanoparticles, replicates within transfected cells to produce sustained antigen expression from a substantially lower RNA dose than conventional mRNA platforms — a property that may be particularly relevant for the low microgram doses tested in Part A. The rationale for pairing with pembrolizumab in Part B rests on the hypothesis that vaccine-primed tumor-specific T cells will encounter a less immunosuppressive microenvironment when PD-1/PD-L1 signaling is blocked, though this interaction has not been characterized for this specific antigen combination in human subjects.
The adjuvant TNBC setting is strategically meaningful. Patients who have completed standard therapy, including neoadjuvant pembrolizumab where eligible under current guidelines, remain at substantial risk of relapse without further immune intervention. Olaparib (Lynparza) is approved for BRCA-mutated TNBC in the adjuvant setting, and capecitabine (Xeloda) is used for residual disease, but neither engages the adaptive immune system. A vaccine capable of establishing durable tumor-antigen-specific memory in the minimal residual disease context would occupy a distinct mechanistic niche from existing options — though whether ITI-5000 can generate clinically meaningful immune responses in post-treatment patients, whose immune systems may be partially depleted by prior chemotherapy, remains to be established in this trial.