Window Study of Intratumoral Mitazalimab in Breast Cancer (WINIT-BC) (WINIT-BC)

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

The goal of this clinical trial is to study the safety, feasibility, histologic and immunological effects of Mitazalimab, a CD40 agonistic antibody, when administered either alone or in combination with PD-1 inhibition prior to surgical resection.

The investigator hypothesizes that preoperative administration of CD40 agonist with or without PD-1 inhibitor intratumorally will demonstrate an acceptable safety profile, will not result in an unplanned delay in surgery, and will lead to increased immune activation.

Subjects will receive a single intratumoral dose of CD40 agonist with or without PD-1 inhibitor 7 or more days prior to surgery and will be followed for safety, feasibility, immune, and pathologic responses.

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Intratumoral Mitazalimab; Drug: Intratumoral Nivolumab

• Study Type: Interventional
• Enrollment (Estimated): 32
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Jennifer Zhang, MD; Phone Number: 215-573-9348; Email: jennifer.zhang@pennmedicine.upenn.edu
• Study Contact Backup: Name: Julia Lewandowski; Phone Number: 215-573-9348; Email: julia.lewandowski@pennmedicine.upenn.edu

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • Hospital of The University of Pennsylvania
      • Contact: Jennifer Zhang, MD; Phone Number: 215-573-9348; Email: jennifer.zhang@pennmedicine.upenn.edu
      • Contact: Julia Lewandowski; Phone Number: 215-573-9348; Email: julia.lewandowski@pennmedicine.upenn.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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. -

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Mitazalimab 22.5 μg/kg; Arm A, Dose Level -1 (DL-1): Mitazalimab 22.5 μg/kg. This dose level will only be explored if ≥ 2 DLTs occur at any time in DL1.	Drug: Intratumoral Mitazalimab; Intratumoral agonistic CD40
Experimental: Mitazalimab 75 μg/kg; Arm A, Dose Level 0 (DL0): Mitazalimab 75 μg/kg	Drug: Intratumoral Mitazalimab; Intratumoral agonistic CD40
Experimental: Mitazalimab 200 μg/kg; Arm A, Dose Level 1 (DL1): Mitazalimab 200 μg/kg	Drug: Intratumoral Mitazalimab; Intratumoral agonistic CD40
Experimental: Mitazalimab 22.5 μg/kg + Nivolumab; Arm B, Dose Level -1 (DL-1): Mitazalimab 22.5 μg/kg + Nivolumab. This dose level will only be explored if ≥ 2 DLTs occur at any time in DL1.	Drug: Intratumoral Mitazalimab; Intratumoral agonistic CD40; Drug: Intratumoral Nivolumab; Checkpoint inhibitor
Experimental: Mitazalimab 75 μg/kg + Nivolumab; Arm B, Dose Level 0 (DL0): Mitazalimab 75 μg/kg + Nivolumab	Drug: Intratumoral Mitazalimab; Intratumoral agonistic CD40; Drug: Intratumoral Nivolumab; Checkpoint inhibitor
Experimental: Mitazalimab 200 μg/kg + Nivolumab; Arm B, Dose Level 1 (DL1): Mitazalimab 200 μg/kg + Nivolumab	Drug: Intratumoral Mitazalimab; Intratumoral agonistic CD40; Drug: Intratumoral Nivolumab; Checkpoint inhibitor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of Grade 3 or higher adverse events as assessed by CTCAE v5.0	Type and severity of adverse events	Within 30 days of treatment
Feasibility of CD40 agonist (Mitazalimab) with/without PD-1 inhibitor (Nivolumab) prior to surgery	Number of successful surgical resection without unanticipated delay in surgery > 14 days after planned surgical date due to treatment-related issues	14 days after planned surgical date

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tumor response rate	Rate of tumors with response (Residual Cancer Burden 0-II)	2 weeks after surgery
Recurrence of disease	Occurrence of a breast cancer recurrence	up to 5 years post surgery
Event-free survival	Length of time between time of surgery and a breast cancer recurrence or death	up to 5 years post surgery
Number of participants with change in serum cytokine levels pre- and post-treatment	Serum cytokine measurement	Prior to treatment and up to 30 days post surgery
Number of participants with changes in tumor immune cell number pre- and post-treatment	10x genomics platform will be used to evaluate for changes in tumor immune cell number pre- and post-treatment	Prior to treatment and up to 30 days post surgery
Number of participants with changes in TCR repertoire in peripheral blood pre- and post-treatment	Comparison of TCR repertoire in peripheral blood via TCR sequencing pre- and post-treatment	Prior to treatment and up to 30 days post surgery
Number of participants with changes in TCR repertoire in tumor pre- and post-treatment	Comparison of TCR repertoire in tumor via TCR sequencing pre- and post-treatment	Prior to treatment and up to 30 days post surgery
Number of patients with FDG PET/CT response or flair after treatment	Change in FDG activity in tumor and/or lymph nodes between baseline (PET0) and post-treatment (PET1) FDG PET/CT scans.	between baseline and 1 week post-treatment
Immunologic effects of CD40 agonist (Mitazalimab) with/without PD-1 inhibitor (Nivolumab)	Immunophenotyping of PBMCs pre- and post-treatment	Prior to treatment and up to 30 days post surgery

Collaborators and Investigators

• Sponsor: Jennifer Zhang
• Collaborators: Alligator Bioscience AB
• Investigators: Principal Investigator: Jennifer Zhang, MD, University of Pennsylvania

Study record dates

Study Major Dates

• Study Start (Actual): April 27, 2026
• Primary Completion (Estimated): April 1, 2028
• Study Completion (Estimated): April 1, 2033

Study Registration Dates

• First Submitted: November 26, 2025
• First Submitted That Met QC Criteria: December 19, 2025
• First Posted (Actual): January 6, 2026

Study Record Updates

• Last Update Posted (Actual): May 6, 2026
• Last Update Submitted That Met QC Criteria: April 29, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: resectable breast cancer
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms
• Other Study ID Numbers: 858844

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No