Phase 1 Study of a Self-amplifying RNA Vaccine (ITI-5000) in Stage 2-3 Triple Negative Breast Cancer

This study tests an investigational cancer vaccine called ITI-5000 in people who have completed standard treatment for early-stage triple-negative breast cancer (TNBC). ITI-5000 is a self-amplifying RNA (saRNA) vaccine that instructs the immune system to recognize and attack cancer cells expressing two proteins found on TNBC cells-HERV-K and CT83-fused with a molecule called LAMP-1 that helps the immune system respond more strongly. The vaccine is delivered inside lipid nanoparticles (LNPs), similar to other approved mRNA vaccines. The study has two parts: * Part A: Participants receive ITI-5000 alone at one of two dose levels (1 µg or 10 µg), given as an injection into the upper arm muscle every 28 days for 3 doses total. The goal is to find the safest dose. * Part B: Participants receive ITI-5000 at the best dose identified in Part A, combined with the following approved immunotherapy drugs pembrolizumab (Keytruda) and either olaparib or capecitabine.

Inclusion Criteria: 1. Applicable to Part A only. Participants must have completed adjuvant pembrolizumab if they were receiving it before enrolling in the study. 2. Applicable to Cohort 3A and Part B only. Participant must have received neoadjuvant chemotherapy with pembrolizumab, then undergone definitive surgery. At the time of surgery, participant must not have achieved pCR. 3. Applicable to Part B only. Participant is currently receiving or is planned to receive standard of care adjuvant therapy, including pembrolizumab in combination with capecitabine or olaparib in accordance with the FDA-approved label, with ≥3 cycles remaining if receiving 200mg Q3W or ≥2 cycles remaining if receiving 400 mg Q6W at the time of first ITI-5000 dose. 4. Adults aged 18 years or over. 5. Participants provided a signed and dated ICF. 6. Participant agrees not to receive any routine vaccinations until at least 30 days after receiving the last study vaccine. 7. TNBC diagnosed as pathologic stage 2-3 according to American Joint Committee on Cancer (AJCC) and confirmed by histological examination, e.g., negative for HER2 as defined by ASCO CAP 2023 guidelines. ER and PgR receptor negative by immunohistochemistry. Participants with BRCA mutations will be allowed. a. Concurrent endocrine therapy (e.g., tamoxifen, aromatase inhibitors, ovarian suppression) is not permitted during study participation. Concurrent CDK4/6 inhibitors (ribociclib/abemaciclib) are not allowed. 8. Applicable to Part A only. Participants with more than 4 weeks since last active therapy (chemotherapy, radiation therapy, or surgery) and 36 months or less following definitive surgery, based on the period of highest risk for recurrence in participants with stages 2-3 TNBC. 9. Applicable to Part A only. Participants completed all planned previous cancer treatment (e.g., chemotherapy, radiation, therapy, surgery). 10. Participant's ECOG performance status is 0 or 1. 11. Participant had no significant ischemic heart disease or myocardial infarction within 3 months before vaccination #1 and has adequate cardiac function during eligibility evaluation, as evidenced by QTc of ≤470 msec for females or ≤450 msec for males assessed by the Fridericia method (QTcF) and evidenced by the average of measurements from triplicate ECGs at the screening visit. a. The eligibility of participants with ventricular pacemakers for whom the QT interval may not be accurately measurable will be determined on a case-by-case basis by the sponsor in consultation with the medical monitor. 12. Participant has an adequate organ function, as evidenced by the following tests conducted within 7 days before enrollment: i. Hematology examination (excluding blood transfusion or use of hematopoietic stimulating agents for correction): 1\. Hemoglobin ≥8.0 g/L 2. Absolute neutrophil count (ANC) ≥1.0 × 109/L 3. Platelet count ≥100 × 109/L ii. Serum biochemistry examination (excluding recent blood transfusion or albumin administration): 1\. Alanine aminotransferase and AST ≤1.5 times the ULN 2. Alkaline phosphatase ≤2.5 ULN 3. Total bilirubin ≤ 1.5 ULN 4. Serum creatinine ≤1.5 ULN, with creatinine clearance ≥ 50 mL/min (calculated using the Cockcroft-Gault formula) 13. Women of childbearing potential have a negative serum pregnancy test within 3 days before vaccination #1, and they and their partners agree to use highly effective methods of contraception during the study and for 6 months after the last administration of the study drug. a. NOTE: A woman is considered of non-childbearing potential if she has had a documented bilateral oophorectomy, tubal ligation, or hysterectomy, or if she is postmenopausal, defined as ≥12 months of spontaneous amenorrhea without an alternative medical cause (with serum FSH confirmation if \