Sac-TMT for Active TNBC Brain Metastases

NCT07458113 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 2000038506
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

This is a multi-site prospective single-arm open-label phase 2 clinical trial including 20 participants with metastatic TNBC and active brain metastases to be treated with sacituzumab tirumotecan 4 mg/kg IV on Days 1, and 15 of every 28-day cycle until disease progression, unacceptable toxicities, consent withdrawal, or death.

Conditions

Metastatic Triple Negative Breast Cancers

Keywords

Sacituzumab tirumotecan; metastatic TNBC; brain metastases

Outcome Measures

Primary Outcomes (1)

• Intracranial response rate determined by Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) in patients with metastatic triple-negative breast cancer and brain metastases.

  To determine the intracranial efficacy of sacituzumab tirumotecan in patients with metastatic triple-negative breast cancer and brain metastases. RANO-BM evaluates treatment response by categorizing results into Complete Response (CR), Partial Response (PR), Stable Disease (SD), or Progressive Disease (PD)

  At screening and every 8 weeks during the treatment period (up to one year)

Secondary Outcomes (7)

• Intracranial clinical benefit rate by Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) in patients with metastatic triple-negative breast cancer and brain metastases.

  At baseline and every 8 weeks during the treatment period (up to 1 year)

• Extracranial objective response rate by Response Evaluation Criteria in Solid Tumors (RECIST 1.1) in patients with metastatic triple-negative breast cancer and brain metastases

  At baseline and every 8 weeks during the treatment period (up to 1 year)

• Extracranial clinical benefit rate by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 in patients with metastatic triple-negative breast cancer and brain metastases

  At baseline and every 8 weeks during the treatment period (up to 2 years)

• Intracranial progression-free survival in patients with metastatic triple-negative breast cancer and brain metastases

  Every 12 weeks during the survival follow up phase (until death or lost to follow up. Participants will be followed for up to 1 year after completing or stopping protocol treatment)

• Overall survival rate in patients with metastatic triple-negative breast cancer and brain metastases

  One year post-treatment

Study Arms (1)

Sacituzumab tirumotecan

EXPERIMENTAL

Sacituzumab tirumotecan will be administered by IV infusion on days 1, and 15 of each 28-day cycle. The duration of the sacituzumab tirumotecan infusions should be 90 minutes (±15 minutes), and infusion-related AEs will be monitored.

Drug: Sacituzumab tirumotecan

Interventions

Sacituzumab tirumotecan DRUG

Sacituzumab tirumotecan should begin within three days of registration. For all study interventions administered based on weight, the participant's weight at screening or at cycle 1, day 1 should be used to calculate the initial dose. The participant's weight will be determined before each dose of sacituzumab tirumotecan. If, at any time throughout the course of treatment, the participant's weight changes by ≥10% from baseline, the dose will be recalculated using this new weight and will be considered the new baseline for all subsequent dosing calculations. The dose(s) of study intervention(s) should be recalculated as needed throughout the study. Dose adjustments for changes in body weight \<10% are permitted per institutional standards. Sacituzumab tirumotecan will be administered by IV infusion on days 1, and 15 of each 28-day cycle. The duration of the sacituzumab tirumotecan infusions should be 90 minutes (±15 minutes), and infusion-related AEs will be monitored.

Sacituzumab tirumotecan

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• An individual of any sex/gender who is at least 18 years of age at the time of providing the informed consent.
• Individuals who are unable to provide informed consent may be included if a Legally Authorized Representative (LAR) is available and able to provide consent on their behalf.
• Histologically and/or cytologically confirmed metastatic triple-negative breast cancer defined by estrogen receptor (ER) expression \<10%, progesterone receptor expression \<10% and HER2-negative status, defined by 0, 1+ or 2+ FISH negative by immunohistochemistry (IHC) by standard pathology.
• Newly diagnosed untreated brain metastases or brain metastases progressing after prior local therapy (including surgery and/or radiation therapy).
• Intracranial measurable disease (RANO-BM criteria).
• Measurable disease is defined as a contrast enhancing lesion that is at least 10 mm in longest diameter, visible on two or more axial slices, and at least 5 mm in diameter perpendicular to the longest diameter. Non-measurable disease includes lesions that are less than 10 mm, those with borders that are not able to be reproducibly measured, dural metastases, bony metastases, leptomeningeal metastases, and cystic-only lesions.
• Note, presence of measurable or non-measurable disease as per RECIST 1.1 assessed by the treating investigator/radiologist not required for eligibility.
• There is no clinical indication for immediate local treatment with surgery or radiation therapy by the treating investigator's assessment.
• Absence of documented leptomeningeal disease (LMD) by cytology. Note: clinical findings or neuroimaging indicating suspected LMD are allowed, so long as cerebrospinal fluid (CSF) cytology is negative.
• Eastern Cooperative Oncology Group Performance Status (ECOG-PS) 0-1.
• No restriction on the number of lines of prior systemic or local anticancer therapies
• Prior therapy must include treatment with an antibody-drug conjugate either per standard of care or as an investigational drug.
• Life expectancy of at least three months (12 weeks) per treating investigator's assessment.
• Adequate treatment washout period before C1D1, as outlined below:
• Major Surgery: minimum washout period of greater than or equal to 4 weeks Therapeutic or palliative stereotactic radiation therapy systemically or to CNS: minimum washout period of greater than or equal to 4 weeks Anticancer systemic therapy with immune checkpoint inhibitors: no washout period Anticancer system therapy including cytotoxic chemotherapy, and antibody-based therapy: minimum washout period of greater than or equal to 3 weeks Targeted agents and small molecules: minimum washout period of greater than or equal to 2 weeks or five half-lives, whichever is longer Strong cytochrome P450 (CYP3A4) inducers/inhibitors: minimum washout period of greater than or equal to 2 weeks Receipt of live, attenuated vaccine (mRNA and replication deficient adenoviral vaccines are not considered attenuated live vaccines): minimum washout period of greater than 30 days. Note: Participants, if enrolled, should not receive live vaccine during the study and up to 30 days after the last dose of study intervention.

You may not qualify if:

• Prior use of sacituzumab tirumotecan.
• Known hypersensitivity to sacituzumab tirumotecan or any of the drug components
• Other concomitant anticancer therapy, including cytotoxic, targeted agents, immunotherapy, antibody, retinoid, or anti-cancer hormonal treatment with the exception of osteoprotective therapies such as denosumab or bisphosphonates.
• Note: Radiotherapy to CNS is allowed during the study if intracranial disease progresses clinically or radiologically without extracranial disease progression, with drug being held prior to radiation and a washout period of three weeks follows the end of radiation prior to resuming therapy.
• A history of uncontrolled seizures (more than two seizures within 28 days prior to registration), CNS disorders, or psychiatric disability judged by the treating investigator to be clinically significant and adversely affecting compliance with study drug.
• Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses
• Pregnant or lactating women.
• Participants requiring concomitant use of chronic systemic (IV or oral) corticosteroids at doses higher than 8 mg dexamethasone per day or other immunosuppressive medications except for managing adverse events; inhaled steroids or intra articular steroid injections are permitted in this study.
• Has a history of documented severe dry eye syndrome, severe Meibomian gland disease and/or blepharitis, or severe corneal disease that prevents/delays corneal healing.
• Has uncontrolled, significant cardiovascular disease or cerebrovascular disease, including New York Heart Association Class III or IV congestive heart failure, unstable angina, myocardial infarction, uncontrolled symptomatic arrhythmia, prolongation of QTcF (Fridericia's formula) interval to \>480 ms, and/or other serious cardiovascular and cerebrovascular diseases within 6 months before the first dose of study intervention.
• Is currently enrolled in the active treatment phase of another therapeutic clinical trial.
• Has a known additional malignancy that is systemically progressing.
• Has an active infection requiring systemic therapy.
• Has a history or current evidence of any condition, therapy, laboratory abnormality, or other circumstance that might confound the results of the study, interfere with the individual's ability to cooperate with the requirements of the study, or interfere with the individual's participation for the full duration of the study, such that it is not in the best interest of the individual to participate, in the opinion of the treating investigator.
• Has had major surgery or significant traumatic injury within four weeks before the first dose of study intervention.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: collaborator
• Translational Breast Cancer Research Consortium: collaborator
• Yale University: lead
• Johns Hopkins University: collaborator

Study Sites (1)

Yale University

New Haven, Connecticut, 06510, United States

Location

MeSH Terms

Conditions

Triple Negative Breast Neoplasms; Brain Neoplasms

Condition Hierarchy (Ancestors)

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Adriana Kahn, MD

  Yale University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Laura Kane

CONTACT

773-369-6904; laura.kane@yale.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: February 18, 2026
• First Posted: March 9, 2026
• Study Start: May 1, 2026
• Primary Completion (Estimated): May 1, 2028
• Study Completion (Estimated): May 1, 2029
• Last Updated: March 9, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)