IL-1 inhibition for early stage triple negative breast cancer

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

This study is testing if a 14-day treatment with Anakinra can change the tumor environment in people with early stage triple negative breast cancer and ER-low positive breast cancer before surgery.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 50 (estimated)
• Ages: 18 Years and up
• Sex: Female
• Sponsor: University Health Network, Toronto (Academic / other)
• Drugs / interventions: chemotherapy, prednisone
• Locations: 2 sites (Toronto, Ontario and 1 other locations)
• Trial ID: NCT06710197 on ClinicalTrials.gov

What this trial studies

This study investigates the effects of a 14-day pre-operative therapy using Anakinra, an IL-1 inhibitor, on the tumor microenvironment in patients with early stage triple negative breast cancer and ER-low positive breast cancer. The research will evaluate changes in key immune biomarkers such as tumor-infiltrating lymphocytes (TILs), tumor-associated macrophages (TAMs), and other inflammatory markers before and after treatment. Paired tissue specimens will be analyzed to assess the impact of the therapy on the tumor microenvironment.

Who should consider this trial

Good fit: Ideal candidates are women over 18 with non-metastatic invasive adenocarcinoma of the breast, specifically those with clinical stage T1a/b N0 triple negative or ER-low breast cancer.

Not a fit: Patients who are male, have HER2 positive breast cancer, or those with certain health conditions such as inflammatory arthritis or significant infections may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could enhance the understanding of immune responses in early breast cancer and potentially improve treatment outcomes.

How similar studies have performed: While this approach is novel in the context of early stage triple negative breast cancer, similar IL-1 inhibition strategies have shown promise in other cancer types.

Eligibility criteria

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.

Where this trial is running

Toronto, Ontario and 1 other locations

• University Health Network-Princess Margaret Cancer Center — Toronto, Ontario, Canada (Recruiting)
• University Health Network — Toronto, Ontario, Canada (Not_yet_recruiting)

Conditions Early Stage Triple Negative ER Low Breast Cancer; WOO