Phase 1 Study of a Self-amplifying RNA Vaccine (ITI-5000) in Stage 2-3 Triple Negative Breast Cancer
brief 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 the following approved immunotherapy drugs pembrolizumab (Keytruda) and either olaparib or capecitabine.
detailed description
This will be a phase 1, FIH, multicenter, open-label, two-part, ascending dose study to evaluate the safety, tolerability, and immune response of the ITI-5000 vaccine in adult participants with TNBC (stage 2-3). The study will be divided into 2 parts: in Part A, participants will receive the ITI-5000 vaccine as a single agent in the post-adjuvant setting, and in Part B, participants will receive the ITI-5000 vaccine in combination with standard of care adjuvant therapy.
Part A will be divided into 2 dose level cohorts - Cohort 1A conducted at the dose of 1 μg (low dose) per vaccination and Cohort 2A conducted at the dose of 10 μg (high dose) per vaccination. In Part A, three vaccinations of ITI-5000 will be administered with a 28-day interval.
The first 3-6 participants will be enrolled sequentially, with the first participant designated as a sentinel participant who will be monitored for 28 days after receiving the first ITI-5000 vaccination before subsequent participants are enrolled. If 0/3 participants experience a DLT, Cohort 2A may proceed. If 1/3 of the participants experience a DLT, the cohort will expand to include 3 additional participants (total of 6). If ≥2/6 participants experience a DLT, the dose will be considered not tolerable, and the cohort will be stopped.
At the conclusion of each cohort, the safety review committee (SRC) will review safety signals and determine a rationale for dose escalation, de-escalation, or potential intermediate doses to be evaluated. The SRC will also determine the dose to be evaluated in Cohort 3A and Part B.
The MTD will be evaluated in Cohort 3A which will enroll up to 15 participants who did not achieve pathological complete response (pCR) following neoadjuvant therapy. This expansion will allow further assessment of safety and immunogenicity in a participant population that is at high risk of disease recurrence.
Part B will evaluate the MTD of ITI-5000 in combination with standard of care (SOC) adjuvant therapy among participants who did not achieve a pathological complete response (pCR) following neoadjuvant therapy.
A safety lead-in group comprising 3 participants will be enrolled at the beginning of Cohort 1B and 2B to assess the safety of the combination treatment. Unlike Part A, no sentinel participant will be required, as the safety of ITI-5000 alone will already have been established in Part A. The safety lead-in will provide an early evaluation of the tolerability of the combination regimen before enrolling additional participants.
official title
A Phase 1, Multicenter, Open-label, First-in-Human Study of ITI-5000 (Self-Amplifying RNA Vaccine) Alone and in Combination With Standard of Care Adjuvant Therapy in Participants With Stage II-III Triple-Negative Breast Cancer (TNBC)