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.

Official title

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

Overview

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.

Interventions

• Biological ES2B-C001
  Vaccine; Administration with or without \[adjuvant\] every third week for a total of five vaccinations.
• Other ISA 51 VD
  Adjuvant; Administration together with ES2B-C001 every third week for a total of five vaccinations.

Primary outcome measures

• To determine the safety, tolerability, maximum tolerated dose (MTD) for ES2B-C001 alone or in combination with [adjuvant]. [Time frame: From enrolment to the end of study at week 18]

Secondary outcome measures (2)

• To investigate the immunogenicity of ES2B-C001 alone or in combination with [adjuvant]. [Time frame: From enrolment to the end of study at week 18]
• To investigate the immunogenicity of ES2B-C001 alone or in combination with [adjuvant]. [Time frame: From enrolment to the end of study at week 18]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

Austria · 3 centers

• Medical University of Graz — Graz
• Ordensklinikum Linz GmbH Barmherzige Schwestern — Linz
• Medical University Of Vienna — Vienna

Identifiers

NCT: NCT06746688 · ES2B-C001-S01 · 2024-516333-12-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗