A Phase 1, 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)
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). 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 an approved immunotherapy drug called pembrolizumab (Keytruda®), every 21 days for 3 doses total.
Detailed description
This is a Phase 1, first-in-human (FIH), multicenter, open-label, two-part, ascending-dose study . Part A evaluates ITI-5000 as a single agent using a modified 3+3 dose-escalation design across two sequential cohorts: * Cohort 1: 1 µg (low dose) per vaccination * Cohort 2: 10 µg (high dose) per vaccination Each cohort begins with a sentinel participant monitored for 28 days after Vaccination #1 before additional participants are enrolled. The dose-limiting toxicity (DLT) observation window is Day 1-28 following Vaccination #1. If ≤1/6 participants experience a DLT, the dose is deemed tolerable and the cohort expands to further characterize safety and immunogenicity. The Safety Review Committee (SRC) reviews safety data between cohorts. After participants complete Part A, without dose-limiting toxicity, Part B will commence. Part B participants will receive ITI-5000 (dose selected after Part A) in combination with pembrolizumab. Pembrolizumab is administered per its FDA-approved label at either: * 200 mg intravenously every 3 weeks (Q3W), or * 400 mg intravenously every 6 weeks (Q6W)
Arms & interventions
- BiologicalITI-5000 TNBC Vaccine
For Arms 1 and 2, Participants receive ITI-5000 at two different doses for Part A. Cohort 1 will receive 1 ug of the vaccine. Cohort two, will receive 10 ug of the ITI-5000 Vaccine if the 1 ug dose is tolerated.
- DrugITI-5000 TNBC Vaccine + Pembrolizumab
Participants will receive ITI-5000 TNBC vaccine at the MTD (determined in Part A) as an intramuscular injection every 21 days for 3 doses, plus pembrolizumab 200 mg IV Q3W or 400 mg IV Q6W per FDA-approved label.
Outcome measures
Primary
Part A: To establish the dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD) of ITI-5000 and to characterize the safety and tolerability of ITI-5000 administered as a single agent. Part B: same as Part A but in combination with Pembrolizumab
Time frame: From enrollment to end of treatment at 6 months
Secondary
Safety and Tolerability of ITI-5000 when administered in combination with pembrolizumab.
Time frame: From enrollment to end of treatment at 12 months
Eligibility criteria
Study locations (2)
START Midwest
Grand Rapids, Michigan, 49546
START Midwest
Grand Rapids, Michigan, 49546