Clinical Trial 21676

• Overview

  Study Title:

  Phase I/II Study of Stereotactic Radiation and Sacituzumab Govitecan with Zimberelimab in the Management of Metastatic Triple Negative Breast Cancer with Brain Metastases (TARGET-TNBC)

  Summary:

  The study is designed as a single-arm, nonrandomized, open-label, phase I/II trial of sacituzumab govitecan (SG) and zimberelimab with SRS among patients with metastatic triple negative breast cancer with brain metastases.

  Objective:

  Primary: Phase I: Evaluate the safety of SRS, SG and zimberelimab among patients with metastatic triple negative breast cancer brain metastases (BCBM). Phase II: Evaluate the PFS of SG and zimberelimab with SRS among patients with metastatic triple negative BCBM. Secondary: Evaluate the intracranial local brain tumor control following SRS, SG and zimberelimab among patients with metastatic triple negative BCBM. Evaluate the intracranial distant brain tumor control following SRS, SG and zimberelimab among patients with metastatic triple negative BCBM. Determine PFS extracranially following SRS, SG and zimberelimab among patients with metastatic triple negative BCBM. Determine overall survival (OS) following SRS, SG and zimberelimab among patients with metastatic triple negative BCBM

• Treatments

  Therapies:

  Immunotherapy; Radiotherapy

  Medications:

  Sacituzumab Govitecan (); Zimberelimab ()

• Inclusion Criteria

  Inclusion Criteria:
  • 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 years or older
  • Triple negative breast cancer; to fulfill the requirement of triple negative disease, a breast cancer must express (less than or equal to 10%), by immunohistochemistry (IHC), of the hormone receptors (estrogen receptor [ER] and progesterone receptor [PR])
  • To fulfill the requirement of HER2 negative disease, a breast cancer must not demonstrate, overexpression of HER2 by either IHC or in-situ hybridization as defined by the ASCO / CAP Guidelines
  • Breast cancer as documented by extracranial tumor biopsy with brain metastases documented from MRI brain imaging or intracranial surgical pathology
  • Eligible for 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 greater than or equal to 0.5 cm for both intact brain metastases and post-operative cavities
  • Maximum diameter of the largest intact brain metastases less than or equal to 4 cm
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2
  • Symptomatic patients having undergone surgery or on stable doses of steroids less than or equal to 8 mg/day dexamethasone will be enrolled
  • Prior treatment with taxane based chemotherapy with anthracyclines (if appropriate)
  • A formalin-fixed, paraffin-embedded tumor tissue block or 10 unstained slides of intracranial/extracranial tumor sample (archival or recent) for biomarker evaluation should be made available and submitted to the central lab for correlative studies. If attempts to obtain archival tissue are unsuccessful the patient may be enrolled.
  • 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

• Exclusion Criteria

  Exclusion Criteria:
  • Presence of leptomeningeal disease
  • All toxicities attributed to prior anticancer therapy must have been resolved to Grade 1 or baseline before administration of study drug(s) other than: a. Toxicities attributed to prior anticancer therapy that either are not expected to resolve and/or result in long-lasting sequelae, such as neuropathy after platinum-based therapy b. Toxicities that are not expected to interfere with study treatment, such as fatigue, alopecia, or grade 2 hematologic toxicity.
  • 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.
  • 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: a. Myocardial infarction or unstable angina pectoris within 6 months of enrollment b. 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 c. NYHA Class III or greater congestive heart failure or left ventricular ejection fraction of > 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 nonbreast 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 or more
  • 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
  • Have had a prior anticancer biologic agent within 4 weeks prior to enrollment or have had prior chemotherapy, targeted small molecule therapy within 2 weeks prior to enrollment and have not recovered from Adverse Events (AEs) at the time of study entry. Patients participating in observational studies are eligible.
  • Have not recovered from AEs due to a previously administered agent. Note: patients with any grade neuropathy or alopecia are an exception to this criterion and will qualify for the study. Note: if patients received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
  • Have previously received topoisomerase 1 inhibitors in the setting of brain metastases.
  • Use of other investigational drugs (drugs not marketed for any indication) within 28 days or 5 half-lives (whichever is longer) of first dose of study drug.
  • Other criteria may apply

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