A Phase I, Multicenter, Open-label, First-in-Human Study of ITI-5000 (Self-Amplifying RNA Vaccine) Alone and in Combination With Pembrolizumab in Participants With Stage II-III Triple-Negative Breast Cancer (TNBC) Who Have Completed Standard Curative Intent Therapy (VITAL-TNBC Study)
Study Identifier:
5000-01-TNBC-P1
CT.gov Identifier:
EudraCT Identifier:
N/A
EU Trial (CTIS) Number:
N/A
Study Contact Information:
Recruiting
Considering participating in a START clinical trial?
Study Summary
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).
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 an approved immunotherapy drug called pembrolizumab (Keytruda®), every 21 days for 3 doses total.
To evaluate the safety, tolerability, and preliminary immunologic activity of ITI-5000 in patients with Stage II–III triple-negative breast cancer, both as a monotherapy and in combination with standard of care adjuvant therapy. To demonstrate the safety and immune activity of ITI-5000 and further establish its potential as a next-generation therapeutic cancer vaccine.
Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
N/A
Phase
The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
Phase I
Sex
Female
Age
18+ years
Study Drug
Drug: Participant Group/Arm Intervention/Treatment Experimental: Part A, Cohort 1 ITI-5000 1 µg Monotherapy
Study Status
Indicates the current recruitment status or the expanded access status
Recruiting
Requirements information
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.
Clinical Study Information for Healthcare Providers
By clicking the button below you will find in-depth information about this clinical trial, including study design, primary and secondary endpoints, and more. This information is intended for healthcare professionals seeking to review the scientific and operational aspects of the study.
Study Locations
Location
Investigator
Status
Condition(s) Treated at Site
Location
START Midwest
Grand Rapids, MI, United States, 49546
Investigator
Nehal Lakhani
Status
Recruiting
Condition(s) Treated at Site