IL-1 Inhibition in Early TNBC (OZM-034)

IL-1 Inhibition for Patients With Early Stage Triple Negative and ER-low Breast Cancer: a Window-of-opportunity Study

This study will examine changes in the tumor microenvironment (TME) induced by 14 days of pre-operative IL-1-inhibiting therapy among patients with early breast cancer (including TNBC and ER-low positive). Key immune biomarkers (TILs, TAMs, NK cells, IL1[beta] and inflammasome component expression) will be evaluated at baseline and following 14 days of IL-1 antagonist therapy (Anakinra) using paired tissue specimens.

Study Overview

• Status: Withdrawn
• Conditions: Early Stage Triple Negative ER Low Breast Cancer
• Intervention / Treatment: Drug: Anakinra (Kineret®)

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • University Health Network-Princess Margaret Cancer Center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• For inclusion in this study, patients must fulfill all the following criteria:

  1. Age > 18 years

  2. Histologically confirmed non-metastatic invasive adenocarcinoma of the breast meeting one of the following criteria:

     i. Clinical stage T1a/b N0 TNBC ii. Clinical stage T1a/b N0 ER-low (1-9%)

  3. Not planned for neoadjuvant chemotherapy

Exclusion Criteria:

Patients who satisfy any of the following exclusion criteria are NOT eligible for this study.

1. Male Gender
2. HER2 positive breast cancer
3. Second primary cancer
4. Multifocal early breast cancer
5. Pre-existing inflammatory arthritis
6. Pregnancy or lactating.
7. Platelets ≤ 100x109/L. ANC ≤ 1.5 x109/L. Hemoglobin ≤ 80 g/L
8. ECOG≥2
9. Clinically significant bacterial, fungal, parasitic or viral infection, which require therapy. Patients with acute bacterial infections requiring antibiotic use should delay screening/enrollment until the course of antibiotic therapy has been completed.
10. Known active hepatitis A, B, C or who are HIV-positive or who are at risk for HBV reactivation. At risk for HBV reactivation is defined as hepatitis B surface antigen positive or anti-hepatitis B core antibody positive. Prior test results obtained as part of standard of care that confirm a subject is immune and not at risk for reactivation (i.e., hepatitis B surface antigen negative, surface antibody positive) may be used for purposes of eligibility and tests do not need to be repeated. Subjects with prior positive serology results must have negative polymerase chain reaction results. Subjects whose immune status is unknown or uncertain must have results confirming immune status before enrollment.
11. Primary immunodeficiency such as X-linked agammaglobulinemia or common variable immunodeficiency.
12. Active and inactive ('latent') tuberculosis infection or suspicion of active tuberculosis. If no suspicion of active tuberculosis, testing is not required.
13. Use of glucocorticoids above the equivalent of 10 mg of prednisone daily within 4 weeks prior to treatment with Anakinra.
14. Major surgery within 4 weeks prior to treatment.
15. History of malignancy in the past 3 years except for treated, early-stage squamous or basal cell carcinoma of the skin or carcinoma-in-situ of the cervix.
16. History or current diagnosis of uncontrolled or significant cardiac disease, including any of the following: a. myocardial infarction within last 6 months. b. uncontrolled congestive heart failure. c. unstable angina within last 6 months. d. exertional angina. e. clinically significant (symptomatic) cardiac arrhythmias (e.g., bradyarrhythmia, sustained ventricular tachycardia, and clinically significant second or third degree AV block without a pacemaker).
17. History of stroke or intracranial hemorrhage within 6 months prior to enrollment.
18. Presence of moderate or severe renal function impairment (estimated creatinine clearance <60 mL/min/1.73m2).
19. Patients with mild, moderate, or severe hepatic impairment or inadequate liver function defined by any of direct bilirubin, alanine amino transferase (ALT), or aspartate aminotransferase (AST)>2.5 x upper limit of normal (ULN). Patients with Child-Pugh score >5 are also excluded.
20. Patients under ongoing treatment with another investigational medication or having been treated with an investigational medication within 30 days of screening or 5 half-lives (whichever is longer) prior to the first dose of investigational product.
21. Significant concurrent, uncontrolled medical condition which, in the investigator's opinion, would jeopardize the safety of the patient or compliance with the protocol.
22. Known hypersensitivity to E-coli derived proteins, Anakinra or any component of the product.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1; Anakinra SC injection 100mg daily x 14 days	Drug: Anakinra (Kineret®); 100 mg/daily subcutaneously
No Intervention: Group 2; Patients will receive standard of care treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To determine the changes in the breast cancer TME in paired patient samples (core biopsy and surgical specimen) before and after 14 days of treatment with the IL-1 receptor antagonist, Anakinra.	2 years

Collaborators and Investigators

• Sponsor: University Health Network, Toronto

Study record dates

Study Major Dates

• Study Start (Actual): March 5, 2025
• Primary Completion (Actual): February 12, 2026
• Study Completion (Actual): February 12, 2026

Study Registration Dates

• First Submitted: November 25, 2024
• First Submitted That Met QC Criteria: November 25, 2024
• First Posted (Actual): November 29, 2024

Study Record Updates

• Last Update Posted (Actual): March 5, 2026
• Last Update Submitted That Met QC Criteria: March 3, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: WOO
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Breast Neoplasms; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Intercellular Signaling Peptides and Proteins; Cytokines; Interleukin 1 Receptor Antagonist Protein
• Other Study ID Numbers: WOO-11-2023

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

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