Isunakinra Plus Pembrolizumab Neoadjuvant Therapy for TNBC

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This is a phase 1/2 open-label, randomized trial in adults with newly diagnosed, locally advanced triple-negative breast cancer. The study evaluates whether isunakinra, an IL-1 receptor antagonist, can modify the tumor microenvironment to enhance response to a PD-1 inhibitor–based neoadjuvant chemotherapy regimen. Primary goals include assessing immunologic changes within the tumor and blood, safety, and preliminary efficacy. Participants are randomized to receive isunakinra at a specified dose in combination with the pembrolizumab-based NAC and standard care. The trial is sponsored by University Health Network with Buzzard Pharmaceuticals and is conducted at Princess Margaret Cancer Centre in Toronto.

Why it matters

Who can join: the full rules

Inclusion Criteria:

1. Age \> 18 years
2. Newly diagnosed, locally advanced, previously untreated and centrally confirmed TNBC, as defined by the most recent American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines, and staging per current AJCC staging criteria for breast cancer as assessed by the investigator based on radiological and/or clinical assessment:

   Clinical stage T1c/N1-N2, T2-4/N0-2
3. Provides core needle biopsies consisting of at least 2 separate tumor cores from the primary tumor to the central laboratory
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
5. Demonstrates adequate organ function
6. Participants of childbearing potential must be willing to use an adequate method of contraception for the course of the study

Exclusion Criteria:

1. Male Gender
2. Luminal A/B and HER2 positive breast cancer
3. Multifocal early breast cancer
4. History of invasive malignancy ≤5 years prior to signing informed consent, except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer
5. Received prior chemotherapy, targeted therapy, and radiation therapy within the past 12 months
6. Has received prior therapy with an anti-PD1, anti-PDL1/-PDL2 agent or with an agent directed to another co-inhibitory T-cell receptor
7. Participated in an interventional clinical study with an investigational compound or device within 4 weeks of randomization for this study
8. Pre-existing inflammatory arthritis
9. Has received a live vaccine within 30 days of the first dose of study treatment
10. Has an active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs)
11. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy (i.e., dosing exceeding 10 mg daily of prednisone or equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment
12. Active or uncontrolled Human Immunodeficiency Virus (HIV), Hepatitis B or Hepatitis C
13. Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis
14. Has an active infection requiring systemic therapy
15. Has significant cardiovascular disease
16. Is pregnant or breastfeeding, or expecting to conceive children within the duration of the study
17. Has a known history of active tuberculosis (TB, Bacillus Tuberculosis)
18. Platelets ≤ 100x109/L. ANC ≤ 1.5 x109/L. Hemoglobin ≤ 80 g/L
19. ECOG≥2
20. History of stroke or intracranial hemorrhage within 6 months prior to enrollment
21. Presence of moderate or severe renal function impairment (estimated creatinine clearance \<60 mL/min/1.73m2)
22. Patients with mild, moderate, or severe hepatic impairment or inadequate liver function (total bilirubin \> 23 umol/L, serum albumin \< 35 g/L, INR \> 1.70)
23. Known hypersensitivity to E-coli derived proteins, isunakinra or any component of the product

Where it's running

• Princess Margaret Cancer Centre
  Toronto, Ontario, Canada Recruiting

Study contacts

• Study coordinator: Dr. Michael Reedijk
• Email: Michael.Reedijk@uhn.ca
• Phone: 416-946-4432

Similar studies

Other studies for the same condition or treatment. Recruiting studies are listed first.

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• BL-B01D1 plus PD-1 therapy vs nab-paclitaxel plus PD-1 therapy in untreated PD-L1-positive locally advanced or metastatic TNBC

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• Self-amplifying RNA vaccine ITI-5000 for stage 2-3 TNBC (two-part study)

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• Predicting immunochemotherapy response in early TNBC

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.