Enhancing ICB Efficacy Through IL-1 Inhibition in TNBC

Prior treatment

• Received prior chemotherapy, targeted therapy, and radiation therapy within the past 12 months
• Has received prior therapy with an anti-PD1, anti-PDL1/-PDL2 agent or with an agent directed to another co-inhibitory T-cell receptor
• Has received a live vaccine within 30 days of the first dose of study treatment
• 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
• History of stroke or intracranial hemorrhage within 6 months prior to enrollment

Other illness

• Luminal A/B and HER2 positive breast cancer
• Multifocal early breast cancer
• 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)
• Active or uncontrolled Human Immunodeficiency Virus (HIV), Hepatitis B or Hepatitis C
• Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis
• Has an active infection requiring systemic therapy
• Has significant cardiovascular disease
• Has a known history of active tuberculosis (TB, Bacillus Tuberculosis)
• Known hypersensitivity to E-coli derived proteins, isunakinra or any component of the product

Lab values

• Platelets ≤ 100x109/L. ANC ≤ 1.5 x109/L. Hemoglobin ≤ 80 g/L
• Presence of moderate or severe renal function impairment (estimated creatinine clearance \<60 mL/min/1.73m2)
• 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)

Age

• 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

Other

• Male Gender
• Participated in an interventional clinical study with an investigational compound or device within 4 weeks of randomization for this study
• Pre-existing inflammatory arthritis
• Is pregnant or breastfeeding, or expecting to conceive children within the duration of the study
• ECOG≥2

• Age \> 18 years
• 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
• Provides core needle biopsies consisting of at least 2 separate tumor cores from the primary tumor to the central laboratory
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Demonstrates adequate organ function
• Participants of childbearing potential must be willing to use an adequate method of contraception for the course of the study