First-in-human, Phase 1 Study of a Self-amplifying RNA Vaccine (ITI-5000) Alone or in Combination With Pembrolizumab in Stage II-- III Triple Negative Breast Cancer Following Standard Therapy ( VITAL-TNBC )

Inclusion criteria

• Age: Adults aged 18 years or over.
• Consent: Provided a signed and dated informed consent form (ICF).
• Diagnosis: Histologically confirmed stage 2-3 triple-negative breast cancer (TNBC), defined as HER2-negative, ER-negative, and PgR-negative by immunohistochemistry. BRCA mutations are allowed.
• Prior Treatment: Completed all planned standard therapy (surgery, chemotherapy, radiation, and/or pembrolizumab as applicable) and be within 36 months of definitive surgery.
• Performance Status: ECOG performance status of 0 or 1.
• Organ Function: Adequate organ function at baseline (hematology, biochemistry, etc.).
• Cardiac Function: No significant ischemic heart disease or myocardial infarction within 3 months before vaccination #1; QTc ≤470 msec for females or ≤450 msec for males.
• Pregnancy: Women of childbearing potential must have a negative serum pregnancy test within 3 days before vaccination #1 and agree to use highly effective contraception during the study and for 123 (Part A) or 137 (Part B) days after last study drug.
• Compliance: Able to attend required study visits and follow-up.
• Understanding: Able to understand and provide signed informed consent per IRB/IEC guidelines.
• Vaccinations: Agrees not to receive routine vaccinations until at least 30 days after the last study vaccine.
• Alternative Therapies: Agrees not to use alternative therapies from the time of informed consent through 30 days following vaccination #3.

Exclusion criteria

• Part B only: Discontinued prior treatment with an immune checkpoint inhibitor (ICI) due to immune-related adverse events (irAEs).
• Recent Surgery/Therapy: Major surgery within 4 weeks before vaccination #1 or received cancer-directed therapy or investigational drug/device within 4 weeks or 5 half-lives before vaccination #1.
• Part B only: Received other PD-1/PD-L1 inhibitors (besides pembrolizumab) without proper washout.
• Toxicities: Unresolved toxicities from prior immunotherapy or chemotherapy (must be ≤ Grade 1 or baseline, or deemed irreversible and not worsened by immunotherapy).
• Medical Illness: Significant medical illness, underlying health condition, or abnormal laboratory finding increasing risk.
• Autoimmune Disease: Active autoimmune disease requiring immunosuppressive treatment within the last year.
• Pregnancy/Lactation: Female participants trying to conceive, pregnant, or lactating.
• Positive Pregnancy Test: Positive serum pregnancy test at screening or positive urine test at baseline.
• Other Trials: Concurrent participation in any other interventional clinical trial.
• Allergies: Known allergies to any components of the study vaccine.
• Anaphylaxis: History of anaphylaxis requiring medical intervention (including severe reactions to other mRNA vaccines).
• Cardiac History: History of stroke, transient ischemic attack, unstable angina, or myocardial infarction within 3 months prior to first dose.
• Myocarditis/Pericarditis: History of myocarditis or pericarditis.
• Heart Failure: Symptomatic congestive heart failure (NYHA Class III or IV), significant arrhythmia, or LVEF \<45%.
• QT Risk: History of risk factors for torsade de pointes or use of QT-prolonging medications.
• Vaccines: Received mRNA or live virus vaccine within 28 days of planned vaccination #1 (flu and COVID boosters prohibited in that window).
• Prior Malignancy: Prior malignancy except adequately treated basal/squamous cell skin cancer, in situ cervical cancer, or disease-free for ≥3 years.
• Organ Transplant: History of organ transplant requiring immunosuppression; unstable HIV/AIDS.
• Hepatitis: Known active hepatitis B or C.
• Compliance: Unable or unwilling to comply with study schedule/procedures.
• Injection/Blood Draw: Contraindication to IM injections or blood draws.