Enhancing ICB Efficacy Through IL-1 Inhibition in TNBC

NCT07698106 | Not Yet Recruiting Phase 1 DMC

• 1 other identifier: RESETT-I
• Study Type: interventional
• Target: 60
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study is a phase I/II open-label randomized clinical trial to examine whether administration of isunakinra (EBI-005), a modified recombinant IL1 receptor antagonist, can sensitize human TNBC to the PD1 inhibitor-pembrolizumab-based neoadjuvant chemotherapy (NAC/P) by changing the tumor microenvironment (TME) via reducing the recruitment of immunosuppressive tumorassociated macrophages (TAMs) and increasing activated cytotoxic T-lymphocytes (CTLs).

Conditions

Triple-Negative Breast Cancer (TNBC)

Outcome Measures

Primary Outcomes (1)

• Outcome-Study will test whether IL1 blockade can reduce TAM and sensitize human TNBCs to ICB. Outcome measure-changes in the TME induced by the addition of isunakinra to NAC/P will be determined.

  The following biomarkers will be evaluated, examining the changes in their expression level between baseline and after 8 weeks of NAC/P ± isunakinra: 1. TAMs 2. Lymphocyte subsets 3. Natural Killer cells 4. Polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) 5. Inflammasome expression 6. Cytokines: IL-1β, IL-1α, IL-6, IL-8 and C-reactive protein (CRP)

  6 years

Study Arms (2)

Group 1-Isunakinra treatment Group

EXPERIMENTAL

Study participants randomized to Group 1 treatment group will receive isunakinra at a dose of 50mg SC daily x 24 weeks in addition to standard pembrolizumab-based neoadjuvant chemotherapy (NAC/P).

Drug: Group 1-Isunakinra

Group 2-Standard of care treatment group

NO INTERVENTION

Study participants randomized to Group 2, the control group, will receive standard pembrolizumab-based neoadjuvant chemotherapy (NAC/P).

Interventions

Group 1-Isunakinra DRUG

isunakinra at a dose of 50mg SC daily x 24 weeks in addition to standard pembrolizumab-based neoadjuvant chemotherapy (NAC/P).

Group 1-Isunakinra treatment Group

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• Male Gender
• Luminal A/B and HER2 positive breast cancer
• Multifocal early breast cancer
• 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
• 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
• Participated in an interventional clinical study with an investigational compound or device within 4 weeks of randomization for this study
• Pre-existing inflammatory arthritis
• Has received a live vaccine within 30 days of the first dose of study treatment
• 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)
• 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
• 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

Sponsors & Collaborators

• Buzzard Pharmaceuticals: collaborator
• University Health Network, Toronto: lead

MeSH Terms

Conditions

Triple Negative Breast Neoplasms

Condition Hierarchy (Ancestors)

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Central Study Contacts

Michael Reedijk, MD

CONTACT

416-946-4432; Michael.Reedijk@uhn.ca

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 24, 2026
• First Posted: July 13, 2026
• Study Start: August 1, 2026
• Primary Completion (Estimated): August 1, 2034
• Study Completion (Estimated): August 1, 2034
• Last Updated: July 13, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share