A First-in-human, Clinical Trial Assessing the Safety of ES2B-C001-S01 With or Without [Adjuvant] in Patients With HER2-expressing Metastatic Breast Cancer.

A First-In-Human Phase I, Open-Label, Dose-Escalating Trial to Assess the Safety, Tolerability and Immunogenicity/Preliminary Antitumor Activity of ES2B-C001 With or Without [Adjuvant] in HER2-expressing Metastatic Breast Cancer

The trial is a first-in-human, phase I, open-label, dose-escalating trial to assess the safety and tolerability of ES2B-C001 combined with or without [adjuvant], in patients with human epidermal growth factor receptor 2 (HER2) expressing metastatic breast cancer.

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer; Breast Cancer Metastatic
• Intervention / Treatment: Other: ISA 51 VD; Biological: ES2B-C001

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Bent U. Frandsen; Phone Number: +4522221019; Email: info@expres2ionbio.com

Study Locations

• Austria
  • Graz, Austria
    • Recruiting
    • Medical University of Graz
    • Contact: Gabriel Rinnerthaler, Assoz. Prof.; Phone Number: +43 316 385 13115; Email: onkologie@medunigraz.at
    • Principal Investigator: Gabriel Rinnerthaler, Assoz. Prof.
  • Linz, Austria, 4010
    • Recruiting
    • Ordensklinikum Linz GmbH Barmherzige Schwestern
    • Contact: Renate Pusch, Dr; Phone Number: +43 732 7677 7225; Email: interne1.bhs@ordensklinikum.at
    • Principal Investigator: Renate Pusch, Dr
  • Vienna, Austria, 1090
    • Recruiting
    • Medical University of Vienna
    • Principal Investigator: Bernd Jilma, Prof.
    • Contact: Bernd Jilma, Prof.; Phone Number: +434040029800; Email: klin-pharmakologie@meduniwien.ac.at

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients aged ≥18 years at screening visit.
• Diagnosis of HER2-expressing locally advanced, unresectable, or metastatic BC, with HER2 IHC level 1+, 2+ (either FISH negative or positive), or IHC level 3+, after undergoing 2-3 lines of anticancer therapy.
• Life expectancy of at least 3 months.
• ECOG performance status 0-2.
• Patients have adequate bone marrow, kidney, liver, heart, and lung function without clinically significant laboratory parameters as judged by the investigator.
• 12-lead ECG without clinically significant abnormalities and no LBBB, QRS duration >140ms, or evidence of prior infarction.
• Recovered from side effects, adverse reactions, or adverse events due to prior therapy and/or surgery; any residual toxicities and toxicities related to current anticancer treatment must be ≤ Grade 2, except for alopecia, neuropathy or lymphoedema.
• If female, non-pregnant, postmenopausal, or practicing reliable contraception.
• If male, sterilized or using reliable contraception.

Exclusion Criteria:

• Any planned intravenous chemotherapy regimens or check point inhibitors, or previous therapy with those agents during the past 1 month and the patients are neutropenic. Maintenance therapy with a stable dose of HER2-directed mAbs or treatment with antibody drug conjugates (ADCs) for metastatic BC is allowed at the discretion of the treating physician.
• Symptomatic CNS metastatic disease requiring treatment with high dose steroids (i.e., above 10 mg of prednisone or equivalent) within 14 days prior to first administration of ES2B-C001 (with or without adjuvant).
• Concurrent or recent (within 21 days or 5 half-lives) involvement in any other clinical trial with an investigational drug, device, or other experimental intervention.
• Concomitant severe or uncontrolled underlying medical and/or mental disease unrelated to the tumor, which in the opinion of the investigator is likely to compromise patient safety and affect the trial's outcome.
• Previous documented coronary artery disease or congestive heart failure (>NYHA II).
• Echocardiography with LVEF <55%.
• Uncontrolled hypertension.
• Active, known, or suspected autoimmune disease, except thyroid conditions sufficiently controlled on thyroid hormone therapy, and controlled insulin dependent diabetes.
• Necessity for long-term immunosuppression (≤ 4 mg dexamethasone may be used transiently).
• Systemic infection requiring intravenous antibiotics within 14 days before dosing.
• Chronic use of anti-viral agents, except for human immunodeficiency virus (HIV) or hepatitis B or C virus (HBV, HCV) treatments.
• History of severe hypersensitivity reactions to any of the trial drug components.
• Has received a live or live-attenuated vaccine within 30 days prior to the first dose of trial treatment. Note: Administration of inactivated or recombinant vaccines/killed vaccines are allowed.
• Birthmarks, tattoos, wounds, or skin conditions on deltoid region/buttocks that may obscure the assessment of injection site reactions.
• Female patients who are pregnant, or lactating.
• Any infection (including SARS-CoV-2), that in the opinion of the investigator would, upon inclusion in the trial, lead to potentially harming patients' safety or integrity.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort C1: 50µg ES2B-C001 with [adjuvant]	Other: ISA 51 VD; Adjuvant; Administration together with ES2B-C001 every third week for a total of five vaccinations.; Biological: ES2B-C001; Vaccine; Administration with or without [adjuvant] every third week for a total of five vaccinations.
Experimental: Cohort C2: 150µg ES2B-C001 with [adjuvant]	Other: ISA 51 VD; Adjuvant; Administration together with ES2B-C001 every third week for a total of five vaccinations.; Biological: ES2B-C001; Vaccine; Administration with or without [adjuvant] every third week for a total of five vaccinations.
Experimental: Cohort C3: 450µg ES2B-C001 with or without [adjuvant]	Other: ISA 51 VD; Adjuvant; Administration together with ES2B-C001 every third week for a total of five vaccinations.; Biological: ES2B-C001; Vaccine; Administration with or without [adjuvant] every third week for a total of five vaccinations.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To determine the safety, tolerability, maximum tolerated dose (MTD) for ES2B-C001 alone or in combination with [adjuvant].	Nature and frequency of dose-limiting toxicities (DLTs).; Incidence, nature and severity of AEs graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0.; Incidence, nature and severity of injection site reactions according to FDA Guidance on Toxicity Grading Scales in Vaccine Trials (FDA, 2007).	From enrolment to the end of study at week 18

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To investigate the immunogenicity of ES2B-C001 alone or in combination with [adjuvant].	Immunogenicity as humoral immune response: Total anti-HER2 Immunoglobulin G (IgG) and IgG lambda titers in sera by enzyme-linked immunosorbent assay (ELISA).	From enrolment to the end of study at week 18
To investigate the immunogenicity of ES2B-C001 alone or in combination with [adjuvant].	Optionally, characterization of anti-HER2 immunoglobulins in selected sera, including isotyping (e.g. IgM, IgG and IgG subclasses IgG1-4, IgD, IgE, IgA) and analysis of HER2 epitope recognition profiles.	From enrolment to the end of study at week 18

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
To determine the preliminary antitumor activity of ES2B-C001 alone or in combination with [adjuvant] observed.	Percentage of patients with measurable disease at baseline achieving Complete Remission (CR) or Partial Response (PR) according to RECIST 1.1 as assessed by the investigator during routine follow up.	From enrolment to the end of study at week 18
To determine the preliminary antitumor activity of ES2B-C001 alone or in combination with [adjuvant] observed.	Percentage of patients with Disease Control Rate (DCR) according to RECIST 1.1 as assessed by the investigator during routine follow up.	From enrolment to the end of study at week 18
To determine the preliminary antitumor activity of ES2B-C001 alone or in combination with [adjuvant] observed.	Overall survival (OS)	From enrolment to the end of study at week 18
To determine the preliminary antitumor activity of ES2B-C001 alone or in combination with [adjuvant] observed.	Progression free survival (PFS) in patients with Stable Disease (SD), or PR, at the time of first dosing of ES2B-C001 alone or in combination with [adjuvant] according to RECIST 1.1.	From enrolment to the end of study at week 18

Collaborators and Investigators

• Sponsor: ExpreS2ion Biotechnologies
• Collaborators: Gouya Insights; KKS MedUni Vienna; VelaLabs
• Investigators: Study Director: Thomas K. Jorgensen, ExpreS2ion Biotechnologies

Study record dates

Study Major Dates

• Study Start (Actual): June 3, 2025
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: December 12, 2024
• First Submitted That Met QC Criteria: December 17, 2024
• First Posted (Actual): December 24, 2024

Study Record Updates

• Last Update Posted (Actual): April 13, 2026
• Last Update Submitted That Met QC Criteria: April 7, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: breast cancer; MBC; metastatic breast cancer
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms
• Other Study ID Numbers: ES2B-C001-S01; 2024-516333-12-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Within the study de-identified patient data will be shared with

• the operational study team, sponsor, auditor and for reporting of safety events to the regulatory agencies and EC
• Data Monitoring Committees/ or other independent committees during the study
• At the end - data listings are part of the Appendices of the CSR which will be shared to regulatory agencies and EC

• IPD Sharing Supporting Information Type: SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No