Pre-surgery intratumoral mitazalimab for resectable breast cancer

Window of Opportunity Study of Intratumoral CD40 Agonist (Mitazalimab) With or Without PD-1 Inhibitor (Nivolumab) in Patients With Resectable Breast Cancer (WINIT-BC)

This test gives a single intratumoral dose of mitazalimab, with or without nivolumab, to adults with resectable stage I–III breast cancer at least 7 days before their planned surgery.

Quick facts

• Phase: Early Phase 1
• Study type: Interventional
• Enrollment: 32 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University of Pennsylvania (Academic / other)
• Drugs / interventions: prednisone, Mitazalimab
• Locations: 1 site (Philadelphia, Pennsylvania)
• Trial ID: NCT07319195 on ClinicalTrials.gov

What this trial studies

This is an early-phase, preoperative window approach delivering a single intratumoral injection of the CD40 agonist mitazalimab, alone or combined with the PD‑1 inhibitor nivolumab, prior to surgical resection. Participants receive the injection seven or more days before their planned surgery and are followed for safety, feasibility, immune changes in the tumor, and pathological response. The trial collects core biopsy and surgical tissue for histologic and immunologic correlative studies. It is conducted at the Hospital of the University of Pennsylvania under institutional oversight.

Who should consider this trial

Good fit: Adults (≥18 years) with resectable stage I–III or recurrent breast cancer planning upfront surgery at the University of Pennsylvania, weighing >40 kg, with adequate organ function and available core biopsy tissue are the intended participants.

Not a fit: Patients with unresectable or metastatic disease, those not able to have surgery at the University of Pennsylvania, or those with poor organ function or contraindications to intratumoral injections or checkpoint inhibitors are unlikely to benefit from this approach.

Why it matters

Potential benefit: If successful, this approach could increase local immune activation in the tumor and inform new preoperative immunotherapy strategies that improve outcomes or guide future studies.

How similar studies have performed: Preoperative and intratumoral immunotherapy approaches have shown promising immune activation in early studies, but intratumoral CD40 agonists combined with PD‑1 blockade remain exploratory with limited prior clinical data.

Eligibility criteria

Inclusion Criteria:

1. Signed and dated written IRB-approved informed consent.
2. Age ≥18 years.
3. Body weight \> 40kg
4. Stage I-III or recurrent resectable breast cancer to be treated with curative-intent
5. Planning to undergo upfront surgery as part of routine clinical care
6. Discussion with the treating or study medical oncologist re: the potential of sending an Oncotype evaluation (if ER+HER2-) on the core needle biopsy sample
7. Availability of the core needle biopsy sample for correlative studies
8. Surgery to be performed at a University of Pennsylvania Hospital
9. Life expectancy of at least 12 weeks.
10. Adequate bone marrow, hepatic, and renal function. ANC (Absolute Neutrophil Count) ≥ 1.5x109 cell/ml, platelets ≥75,000 /mm3, hemoglobin ≥9.0 g/dL, total serum bilirubin within 1.5 x upper limit of normal (ULN) unless Gilbert's, AST/ALT, within 2.5 x ULN, Albumin ≥3g/dL, and all tests performed within 4 weeks prior to administration of Study Treatment.
11. ECG with no clinically significant findings as assessed by the investigator.
12. ECOG (Eastern Cooperative Oncology Group) performance status of 0-1.
13. Female patients of childbearing potential who are not abstinent and intend to be sexually active with a non-sterilized male partner must use at least 1 highly effective method of contraception from the time of screening throughout the total duration of the drug treatment and the drug washout period (90 days after therapy). Non-sterilized male partners of a female patient of childbearing potential must use male condom plus spermicide throughout this period. Female patients should also refrain from breastfeeding throughout this period.
14. Able and willing to comply with all study procedures.

Exclusion Criteria:

1. Metastatic disease.
2. Planned neoadjuvant therapy, i.e., not undergoing upfront surgery.
3. Known history of hepatitis B or C with active viral replication.
4. Administration of any live vaccine within 28 days of first dose of study treatment.
5. Prior CD40 or anti-PD-1 agonist therapy.
6. Participation in another interventional clinical trial within 30 days before receiving first dose of study treatment. However, the subject may participate in observational studies.
7. Any illness or condition that in the opinion of the investigator may affect the safety of the subject or the evaluation of any study endpoint.
8. Current or prior use of immunosuppressive medication within 14 days before study treatment. The following are exceptions to this criterion:

   1. Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection)
   2. Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent
9. Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of IP.
10. History of allogenic organ transplantation
11. Active or prior documented autoimmune disease. Examples include inflammatory bowel disease \[e.g., colitis or Crohn's disease\], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome \[granulomatosis with polyangiitis\], Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.\]. The following are exceptions to this criterion:

    1. Patients with vitiligo or alopecia
    2. Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement or type 1 DM controlled with insulin
    3. Any chronic skin condition that does not require systemic therapy
    4. Patients without active autoimmune disease in the last 5 years may be included but only after consultation with the study physician
    5. Patients with celiac disease controlled by diet alone
12. Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent
13. History of another active malignancy except for non-melanoma skin cancer, lentigo maligna or other carcinoma in situ
14. History of active primary immunodeficiency
15. Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients.
16. Body weight \> 110 kg.
17. Actively breastfeeding. -

Where this trial is running

Philadelphia, Pennsylvania

• Hospital of the University of Pennsylvania — Philadelphia, Pennsylvania, United States (Recruiting)

Study contacts

• Principal investigator: Jennifer Zhang, MD — University of Pennsylvania
• Study coordinator: Jennifer Zhang, MD

Conditions Breast Cancer; resectable breast cancer