Sacituzumab Govitecan and Zimberelimab w/SRS in the Management of Metastatic Triple Negative Breast Cancer With Brain Metastases

NCT06238921 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: MCC-21676
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase I/II Study to determine the safety and efficacy of Sacituzumab Govitecan and Zimberelimab with stereotactic radiation (SRS) in participants with metastatic triple negative breast cancer with brain metastases, compared to treatment with Sacituzumab Govitecan alone.

Conditions

Breast Cancer; Triple Negative Breast Cancer

Outcome Measures

Primary Outcomes (2)

• Phase I: Neurologic Toxicity

  Neurologic Toxicity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v5). A Neurologic Toxicity will be defined as any Grade 3 or higher toxicity that occurs during the Dose Limiting Toxicity evaluation period. Toxicity that is clearly and directly related to the primary disease or to another etiology is excluded from this definition. * Symptomatic radionecrosis, defined by surgical pathology or multidisciplinary evaluation. * Grade ≥ 3 headaches * Grade ≥ 3 memory impairment * New onset grade ≥ 3 seizures

  Up to 9 Weeks

• Phase II: Progression Free Survival (PFS)

  Evaluate the PFS of SG and zimberelimab with SRS among patients with metastatic triple negative breast cancer. PFS is time from the date of start of treatment to the investigator-determined date of progression or death due to any cause, whichever occurs first.

  Up to 12 Months

Secondary Outcomes (5)

• Phase II: Intracranial Progression Free Survival (PFS)

  Up to 12 Months

• Phase II: Extracranial Progression Free Survival (PFS)

  Up to 33 Months

• Phase II: Overall Survival (OS)

  Up to 33 Months

• Phase II: Local Brain Control

  Up to 33 Months

• Phase II: Distant Brain Control

  Up to 33 months

Study Arms (1)

SG + Zimberelimab with SRS

EXPERIMENTAL

Treatment will be initiated with SRS followed 1 week later by SG on days 1 and 8 (10mg/kg) with zimberelimab on day 1 (360 mg IV) repeated every 3 weeks follow-up imaging response assessments will be conducted at q9 week intervals.

Radiation: Stereotactic Radiation; Drug: Zimberelimab; Drug: Sacituzumab govitecan

Interventions

Stereotactic Radiation RADIATION

Stereotactic Radiation to intact brain metastases or post-operative cavity.

SG + Zimberelimab with SRS

Zimberelimab DRUG

One week +/- 4 days following receipt of SRS, zimberelimab 360 mg IV will be administered. This will be followed by zimberelimab 360 mg IV every 3 weeks.

SG + Zimberelimab with SRS

Sacituzumab govitecan DRUG

SG will be administered on days 1 and 8 (10 mg/kg) of 21 day treatment cycles. This will be one week +/- 4 days following receipt of SRS for the first dose.

Also known as: Trodelvy

SG + Zimberelimab with SRS

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of signed and dated Informed Consent Form (ICF).
• Stated willingness to comply with all study procedures and availability for the duration of the study.
• Age ≥ 18.
• Triple negative breast cancer; to fulfill the requirement of triple negative disease, a breast cancer must express (≤ 10%), by immunohistochemistry (IHC), of the hormone receptors (estrogen receptor \[ER\] and progesterone receptor \[PR\]).
• Breast cancer as documented by extracranial tumor biopsy with brain metastases documented from MRI brain imaging or intracranial surgical pathology.
• Eligible for Stereotactic radiosurgery (SRS) to brain metastases or to the post-operative bed.
• Measurable brain disease per RANO-BM criteria1 that can be measured in at least one dimension as ≥ 0.5 cm for both intact brain metastases and post-operative cavities.
• Maximum diameter of the largest intact brain metastases ≤ 4 cm.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2.
• Symptomatic patients having undergone surgery or on stable doses of steroids ≤ 8 mg/day dexamethasone will be enrolled.
• Prior treatment with taxane based chemotherapy with anthracyclines.
• Individuals with prior SRS/fractioned stereotactic radiotherapy (FSRT) treatment will be allowed if active measurable disease has not previously been treated with radiation therapy.
• Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test within 24 hours prior to the administration of each dose of study agent.
• Male and female patients of childbearing potential who engage in heterosexual intercourse must agree to use specified method(s) of contraception.

You may not qualify if:

• Presence of leptomeningeal disease.
• Women who are pregnant or breastfeeding.
• Known history of HIV-1 or 2 with detectable viral load.
• Active, known, or suspected autoimmune disease. Patients with an autoimmune paraneoplastic syndrome requiring concurrent immunosuppressive treatment are excluded. Exceptions are patients with type I diabetes mellitus, hypothyroidism only requiring thyroid replacement therapy, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
• History of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
• Met any of the following criteria for cardiac disease:
• Myocardial infarction or unstable angina pectoris within 6 months of enrollment
• History of serious ventricular arrhythmia (ie, ventricular tachycardia or ventricular fibrillation), high-grade atrioventricular block, or other cardiac arrhythmias requiring antiarrhythmic medications (except for atrial fibrillation that is well controlled with antiarrhythmic medication); history of QT interval prolongation
• New York Heart Association (NYHA) Class III or greater congestive heart failure or left ventricular ejection fraction of \< 40%
• Any patient requiring supplemental oxygen therapy.
• Have an active serious infection requiring antibiotics.
• Have active chronic inflammatory bowel disease (ulcerative colitis, Crohn's disease) or GI perforation within 6 months of enrollment.
• Patients with prior history of non-breast cancer malignancies are excluded except in the case of adequately treated basal cell cancer, squamous cell skin cancer, chronic lymphocytic leukemia, or other cancers in remission not receiving active therapy for ≥ 2 years.
• Known medical condition that, in the investigator's opinion, would increase the risk associated with study participation or study drug(s) administration or that would interfere with the interpretation of safety results.
• Major surgery or significant traumatic injury that has not been recovered from by 14 days before the initiation of study drug.

Sponsors & Collaborators

• H. Lee Moffitt Cancer Center and Research Institute: lead
• Gilead Sciences: collaborator

Study Sites (1)

Moffitt Cancer Center

Tampa, Florida, 33612, United States

RECRUITING

Related Links

• Moffitt Cancer Center Clinical Trials website

MeSH Terms

Conditions

Breast Neoplasms; Triple Negative Breast Neoplasms

Interventions

Radiosurgery; zimberelimab; sacituzumab govitecan

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Kamran Ahmed, MD

  Moffitt Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Michelle DeJesus

CONTACT

813-745-6911; Michelle.DeJesus@moffitt.org

Kamran Ahmed, MD

CONTACT

kamran.ahmed@moffitt.org

Study Design

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

Study Record Dates

• First Submitted: January 25, 2024
• First Posted: February 2, 2024
• Study Start: December 19, 2024
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): February 1, 2027
• Last Updated: December 5, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)