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

NCT07652242 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 5000-01-TNBC-P1
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 2

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.

Conditions

Triple Negative Breast Cancer (TNBC)

Keywords

TNBC; saRNA; Pembrolizumab; Phase I Clinical Trial; Immunotherapy; HERV-K; First in Human (FIH); CT83

Outcome Measures

Primary Outcomes (1)

• Incidence of Dose-Limiting Toxicities as Assessed by CTCAE v5.0

  21-28 days after the first vaccination

Secondary Outcomes (1)

• Incidence and severity of TEAEs, SAEs, treatment-related TEAEs, AESIs, and clinically significant abnormalities in laboratory parameters, vital signs, and ECGs

  From first dose through end of safety follow-up

Study Arms (5)

Part A, Cohort 1 ITI-5000 1 µg Monotherapy

EXPERIMENTAL

Participants receive ITI-5000 1 µg as an intramuscular injection every 28 days for 3 doses.

Biological: ITI-5000 mRNA Vaccine

Part A, Cohort 2 ITI-5000 10 µg Monotherapy

EXPERIMENTAL

Participants receive ITI-5000 10 µg as an intramuscular injection every 28 days for 3 doses.

Biological: ITI-5000 mRNA Vaccine

Part B ITI-5000 and Pembrolizumab + Olaparib

EXPERIMENTAL

Participants receive ITI-5000 at the dose determined in Part A as an injection every 21 days for 3 doses. Participants will also receive pembrolizumab 200 mg or 400 mg per FDA-approved package insert plus Olaparib.

Drug: Pembrolizumab; Drug: Olaparib; Biological: ITI-5000 MTD (Maximum Tolerated Dose)

Part A, Cohort 3 ITI-5000 Monotherapy Expansion

EXPERIMENTAL

Participants receive ITI-5000 Maximum Tolerated Dose (MTD) as an intramuscular injection every 28 days for three doses

Biological: ITI-5000 MTD (Maximum Tolerated Dose)

Part B ITI-5000 and Pembrolizumab+Capecitabine

EXPERIMENTAL

Participants receive ITI-5000 at the dose determined in Part A as an injection every 21 days for three doses. Participants also receive Pembrolizumab 200 mg or 400 mg per FDA-approved package insert plus Capecitabine

Drug: Pembrolizumab; Drug: Capecitabine; Biological: ITI-5000 MTD (Maximum Tolerated Dose)

Interventions

ITI-5000 mRNA Vaccine BIOLOGICAL

Participants receive ITI-5000. Cohort 1 will receive 1 ug of vaccine

Part A, Cohort 1 ITI-5000 1 µg Monotherapy

Pembrolizumab DRUG

Participants will receive ITI-5000 as an intramuscular injection every 21 days for 3 doses. Participants will also receive pembrolizumab as per the FDA-approved package insert.

Part B ITI-5000 and Pembrolizumab + Olaparib; Part B ITI-5000 and Pembrolizumab+Capecitabine

Olaparib DRUG

Participants will receive Olaparib in combination with Pembrolizumab and ITI-5000

Part B ITI-5000 and Pembrolizumab + Olaparib

Capecitabine DRUG

Participants will receive Capecitabine in combination with Pembrolizumab and ITI-5000

Part B ITI-5000 and Pembrolizumab+Capecitabine

ITI-5000 MTD (Maximum Tolerated Dose) BIOLOGICAL

Participants receive ITI-5000 Maximum Tolerated Dose (MTD)

Part A, Cohort 3 ITI-5000 Monotherapy Expansion; Part B ITI-5000 and Pembrolizumab + Olaparib; Part B ITI-5000 and Pembrolizumab+Capecitabine

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Applicable to Part A only. Participants must have completed adjuvant pembrolizumab if they were receiving it before enrolling in the study.
• 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.
• 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.
• Adults aged 18 years or over.
• Participants provided a signed and dated ICF.
• Participant agrees not to receive any routine vaccinations until at least 30 days after receiving the last study vaccine.
• 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.
• 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.
• Applicable to Part A only. Participants completed all planned previous cancer treatment (e.g., chemotherapy, radiation, therapy, surgery).
• Participant's ECOG performance status is 0 or 1.
• 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.
• 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):

You may not qualify if:

• Applicable to Part B only. Participant discontinued prior treatment with an ICI due to irAEs.
• Participant underwent major surgery within 4 weeks before the planned day of vaccination #1 or received any other investigational drug or device within 4 weeks or 5 half-lives of that agent (whichever is shorter) before the planned day of Vaccination #1.
• i. Applicable to Part A only. Participant received cancer-directed therapy (chemotherapy, radiotherapy, biologic or immunotherapy, etc.) within 4 weeks or 5 half-lives of that agent (whichever is shorter) before the planned day of Vaccination #1. ii. Applicable to Part B only. Participants who received any PD-1 or PD-L1 inhibitor other than pembrolizumab will be excluded unless they have completed a washout period of ≥ 4 weeks or 5 half-lives of that agent (whichever is shorter) before Vaccination #1.
• Participant has toxicities due to prior immunotherapy. For the participant to be eligible, these toxicities must either have returned to ≤ Grade 1 or baseline or been deemed irreversible and in the opinion of the investigator not worsened by immunotherapy (e.g., ICI-endocrinopathies). Participants with any cardiac toxicities (regardless of the grade, etc.) will be excluded.
• Participant has toxicities due to prior chemotherapy that have not been resolved or considered stable and clinically manageable (e.g., neuropathies). Participants with any cardiac toxicities will be excluded.
• Participant has a significant medical illness, underlying health condition, or abnormal laboratory finding that, in the investigator's opinion, would increase the risk of participating in the study.
• Participants with an active autoimmune disease requiring immunosuppressive treatment within the last year (excluding irAEs), such as chronic prolonged systemic corticosteroid use (defined as corticosteroid use lasting one month or more).
• Female participants who are trying to conceive, are pregnant, or lactating.
• A positive serum pregnancy test at screening and/ or a positive human chorionic gonadotropin (hCG) urine test at baseline in women of childbearing potential.
• Participant concurrently participates in any other interventional clinical trial.
• Participant has known allergies to any of the components of the study vaccine.
• Participant has a history of anaphylaxis requiring medical intervention (including severe reactions to other mRNA vaccines, such as those against SARS-COV-2, etc.).
• Participant has a history of stroke, transient ischemic attack, unstable angina, or myocardial infarction within 3 months prior to the first dose of study treatment.
• Participant has a history of myocarditis or pericarditis.
• Participant has symptomatic congestive heart failure according to New York Heart Association (NYHA) classification, Class III or IV (per NYHA Classification), clinically significant cardiac arrhythmia, or a known left ventricular ejection fraction \<45%.

Sponsors & Collaborators

• Immunomic Therapeutics, Inc.: lead

Study Sites (2)

START Midwest

Grand Rapids, Michigan, 49546, United States

RECRUITING

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

RECRUITING

MeSH Terms

Conditions

Triple Negative Breast Neoplasms

Interventions

pembrolizumab; olaparib; Capecitabine; Maximum Tolerated Dose

Condition Hierarchy (Ancestors)

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Toxicity Tests; Investigative Techniques; Toxicological Phenomena; Pharmacological and Toxicological Phenomena; Physiological Phenomena

Central Study Contacts

Scott L Wehage, M.S.

CONTACT

301-968-3501; clinicaloperations@immunomix.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is a Phase 1, multicenter, open-label, parallel assignment clinical trial evaluating the safety, tolerability, and immunogenicity of ITI-5000, a self-amplifying RNA vaccine, administered alone or in combination with pembrolizumab plus either OIaparib or Capecitabine in adults with stage II-III triple-negative breast cancer (TNBC) who have completed standard curative-intent therapy; participants are assigned to either low- or high-dose ITI-5000 monotherapy cohorts (Part A) or to a combination therapy cohort with pembrolizumab at the maximum tolerated dose determined from Part A (Part B), with the primary objectives focused on dose-limiting toxicities and safety, and exploratory endpoints assessing immune response.

Study Record Dates

• First Submitted: June 11, 2026
• First Posted: June 17, 2026
• Study Start: June 1, 2026
• Primary Completion (Estimated): February 1, 2028
• Study Completion (Estimated): August 1, 2028
• Last Updated: July 30, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)