Triple-Negative Breast Cancer (TNBC)Phase 1/2NCT07698106
Enhancing ICB Efficacy Through IL-1 Inhibition in TNBC
A Phase 1/2 study testing Group 1-Isunakinra in people with Triple-Negative Breast Cancer (TNBC), run by University Health Network, Toronto.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Triple-Negative Breast Cancer (TNBC)
- What is being tested?
- Group 1-Isunakinra
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- No sites listed yet
- Study dates
- Oct 2026to Aug 2034
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 23Show fewer
- 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
- Is pregnant or breastfeeding, or expecting to conceive children within the duration of the study
- Has a known history of active tuberculosis (TB, Bacillus Tuberculosis)
- Platelets ≤ 100x109/L. ANC ≤ 1.5 x109/L. Hemoglobin ≤ 80 g/L
- ECOG≥2
- History of stroke or intracranial hemorrhage within 6 months prior to enrollment
- 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)
- Known hypersensitivity to E-coli derived proteins, isunakinra or any component of the product
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Rebooting Sensitivity to Checkpoint Blockade Therapy in Triple-Negative Breast Cancer With Isunakinra (RESETT- I)
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).
Read the detailed description
Pre-clinical work has found that tumor cell IL-1β drives TAM recruitment, immunosuppression, and tumor progression in TNBC. In fact, experimental evidence, across most cancer types, supports a tumor-promoting role for IL-1β making IL-1β a target with clear therapeutic potential. Roles for IL-1β in growth, invasion and angiogenesis, metastases, stemness and epithelial-mesenchymal transition (EMT) and tumoral recruitment of TAMs and other pro-tumoral inflammatory cells have been extensively described, and IL-1β upregulation is generally associated with poorer prognosis. The best available clinical information suggests that targeting IL-1β reduces cachexia and remarkably is associated with a greater than 50% reduction of death from all cancers (phase 3 Cantos trial, testing the IL-1β inhibitor canakinumab (Ilaris®) to treat heart failure in a cohort of 10,061 patients). We are the first to suggest that TNBCs are the "perfect storm" for IL-1β production, with Notch providing IL-1β priming and the inflammasome ensuring cleavage, making TNBC an ideal candidate for IL-1β blockade. Supporting this, our most recent pre-clinical work shows that IL1β antagonists can synergize with ICB to eliminate TNBC.
This study is a phase I/II open-label randomized clinical trial evaluating the immunologic effects within the tumor, microenvironment, and host blood of patients treated with either: Group 1 Study participants randomized to Group 1 treatment group will receive isunakinra at a dose of 25mg SC daily x 24 weeks in addition to standard pembrolizumab-based neoadjuvant chemotherapy (NAC/P). Group 2 Study participants randomized to Group 2, the control group, will receive standard pembrolizumab-based neoadjuvant chemotherapy (NAC/P).
A total of 60 patients will be recruited across 3 institutions, randomized 1:1 to treatment (n=30) versus control (n=30).
The proposed study may provide important data regarding the mechanism of action, safety, feasibility and efficacy of isunakinra when added to NAC/P. It will inform sample size for a definitive phase 3 study designed to prove that isunakinra improves patient outcome.
- Conditions
- Triple-Negative Breast Cancer (TNBC)
- Being tested
- Group 1-Isunakinra
- Medical subject headings
- Triple Negative Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Group 1-IsunakinraDrug
isunakinra at a dose of 25mg SC daily x 24 weeks in addition to standard pembrolizumab-based neoadjuvant chemotherapy (NAC/P).
| Study group | Role | What they receive |
|---|---|---|
| Group 1-Isunakinra treatment Group | Experimental | Study participants randomized to Group 1 treatment group will receive isunakinra at a dose of 25mg SC daily x 24 weeks in addition to standard pembrolizumab-based neoadjuvant chemotherapy (NAC/P). Receives: 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). |
What is being measured
The primary outcome is the main question the study is designed to answer.
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:
- TAMs
- Lymphocyte subsets
- Natural Killer cells
- Polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs)
- Inflammasome expression
- Cytokines: IL-1β, IL-1α, IL-6, IL-8 and C-reactive protein (CRP)
Measured: 6 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jul 2026
- Study startOct 2026 (estimated)
- Primary completionAug 2034 (estimated)
- Study completionAug 2034 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Triple-Negative Breast Cancer (TNBC)Studies of the same condition, open and under way.
- More trials run by University Health Network, TorontoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Health Network, Toronto
- Sponsor type
- University, hospital or other
- Collaborators
- Buzzard Pharmaceuticals
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07698106
- Sponsor's protocol ID
- RESETT-I
- Status last verified
- Oct 2026
- First submitted
- 24 Jun 2026
- Last updated
- 22 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Rebooting Sensitivity to Checkpoint Blockade Therapy in Triple-Negative Breast Cancer With Isunakinra (RESETT- I)
- ClinicalTrials.gov ID
- NCT07698106
- Acronym / sponsor ID
- RESETT-I
- Conditions
- Triple-Negative Breast Cancer (TNBC)
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- University Health Network, TorontoUniversity, hospital or other
- Collaborators
- Buzzard Pharmaceuticals
- Study start
- Oct 2026 (estimated)
- Primary completion
- Aug 2034 (estimated)
- Study completion
- Aug 2034 (estimated)
- First posted
- 13 Jul 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed description
Pre-clinical work has found that tumor cell IL-1β drives TAM recruitment, immunosuppression, and tumor progression in TNBC. In fact, experimental evidence, across most cancer types, supports a tumor-promoting role for IL-1β making IL-1β a target with clear therapeutic potential. Roles for IL-1β in growth, invasion and angiogenesis, metastases, stemness and epithelial-mesenchymal transition (EMT) and tumoral recruitment of TAMs and other pro-tumoral inflammatory cells have been extensively described, and IL-1β upregulation is generally associated with poorer prognosis. The best available clinical information suggests that targeting IL-1β reduces cachexia and remarkably is associated with a greater than 50% reduction of death from all cancers (phase 3 Cantos trial, testing the IL-1β inhibitor canakinumab (Ilaris®) to treat heart failure in a cohort of 10,061 patients). We are the first to suggest that TNBCs are the "perfect storm" for IL-1β production, with Notch providing IL-1β priming and the inflammasome ensuring cleavage, making TNBC an ideal candidate for IL-1β blockade. Supporting this, our most recent pre-clinical work shows that IL1β antagonists can synergize with ICB to eliminate TNBC.
This study is a phase I/II open-label randomized clinical trial evaluating the immunologic effects within the tumor, microenvironment, and host blood of patients treated with either: Group 1 Study participants randomized to Group 1 treatment group will receive isunakinra at a dose of 25mg SC daily x 24 weeks in addition to standard pembrolizumab-based neoadjuvant chemotherapy (NAC/P). Group 2 Study participants randomized to Group 2, the control group, will receive standard pembrolizumab-based neoadjuvant chemotherapy (NAC/P).
A total of 60 patients will be recruited across 3 institutions, randomized 1:1 to treatment (n=30) versus control (n=30).
The proposed study may provide important data regarding the mechanism of action, safety, feasibility and efficacy of isunakinra when added to NAC/P. It will inform sample size for a definitive phase 3 study designed to prove that isunakinra improves patient outcome.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group 1-Isunakinra treatment Group | Experimental | Drug: Group 1-IsunakinraStudy participants randomized to Group 1 treatment group will receive isunakinra at a dose of 25mg SC daily x 24 weeks in addition to standard pembrolizumab-based neoadjuvant chemotherapy (NAC/P). |
| 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). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (23 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Group 1-Isunakinraisunakinra at a dose of 25mg SC daily x 24 weeks in addition to standard pembrolizumab-based neoadjuvant chemotherapy (NAC/P). | Drug | Group 1-Isunakinra treatment Group |
Primary outcome
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.
Time frame: 6 years
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)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Oct 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Group 1-Isunakinra in people with Triple-Negative Breast Cancer (TNBC), run by University Health Network, Toronto.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 22 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Michael Reedijk, MD (416-946-4432, Michael.Reedijk@uhn.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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. (time frame: 6 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Oct 2026.