Study Assessing QBS72S For Treating Brain Metastases of Breast Cancer

This is an interventional treatment trial for Brain Metastases Read More

Inclusion Criteria:

• The participant must have a histologically confirmed TNBC primary tumor, either confirmed via primary specimen or via metastasis site, having developed brain metastases (parenchymal or LM) after a prior cytotoxic chemotherapy regimen. TNBC is defined as breast cancer that is estrogen receptor (ER)-negative (< 5% expression); progesterone receptor (PR)-negative (< 5% expression); and human epidermal growth factor receptor 2 (HER2)-negative (negative FISH result or a HER2 receptor IHC result of 0 or 1+).There is no restriction on prior cycles of systemic therapy for metastatic breast cancer.

• One of the following:

  1. A participant with brain parenchymal tumors must have at least one untreated tumor > 3 mm2 that can be seen on 2 or more separate acquired sequences.
  2. A participant with LM disease must have a positive cytology or MRI evidence of LMD. The presence of parenchymal brain metastases does not exclude these participants from Cohort 2.
• The participant must be 18 years old or older.
• The participant must have a Karnofsky Performance Status (KPS) of 60 or above.
• The participant must receive an MRI with contrast that supports the presence of parenchymal brain metastases or leptomeningeal disease.
• The participant must be on stable doses of corticosteroids and anticonvulsants for greater than or equal to 5 days prior to obtaining the baseline Gd-MRI of the brain.

• The participant must have completed treatment greater than or equal to:

  1. 14 days for small molecules and non-cytotoxic systemic drugs e.g., PARP inhibitors
  2. 21 days for checkpoint inhibitors and monoclonal antibodies, e.g., atezolizumab, pembrolizumab, and bevacizumab, and cytotoxic chemotherapy
  3. 28 days for investigational drugs and radiotherapy; or
  4. 1 dosing cycle for other interventions, prior to first dose of QBS72S All clinically significant toxicities excluding alopecia must have resolved to less than or equal to CTCAE v5.0 Grade 1. Participation in long term follow up is allowed if no procedures will be performed which may interfere with the interpretation of study results.

• The participant must have adequate bone marrow function, including:

  1. ANC ≥ 1,500/mm3 or ≥ 1.5 x 109/L
  2. Platelets ≥ 100,000/ mm3 or ≥ 100 x 109/L
  3. Hemoglobin ≥ 9 g/dL
• The participant must have adequate renal function, including serum creatinine ≤ 1.5 x ULN or estimated creatinine clearance ≥ 50 mL/min. In equivocal cases, a 24-hour urine collection test can be used to estimate the creatinine clearance more accurately.

• The participant must have adequate liver function, including:

  1. Total serum bilirubin ≤ 1.5 x ULN unless the participant has documented Gilbert syndrome who must have a total bilirubin < 3.0 mg/dl
  2. Aspartate and Alanine aminotransferase (AST and ALT) ≤ 2.5 x ULN; ≤ 5.0 x ULN if there is liver involvement by the tumor
• Any participant physiologically capable of becoming pregnant or getting a partner pregnant must agree to use highly effective contraception during study treatment and for 7 months after study discontinuation.
• Participants or their designated advocates must be willing to and capable of providing informed consent and willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures.

Exclusion Criteria:

• Participants currently using any anticancer therapy (including radiotherapy) or using any investigational agent(s), except those explicitly documented allowable by the PI.
• Participants with any other active malignancy within 3 years prior to enrollment, except for adequately treated basal cell or squamous cell skin cancer or carcinoma in situ.
• Participants taking a dexamethasone dose greater than 8 mg per day as a stable or decreasing dose. No escalation of dexamethasone dosing is allowed in the past 14 days prior to screening.
• Participants who received major surgery or brain surgery within 28 days or fewer. Minor procedures such as tumor biopsy are allowed with written approval of the PI.
• Participants with tumors within the brainstem or spinal cord parenchyma. LMD is not an exclusion criterion.
• Participants with intolerance to or who have had a severe (Grade 3) allergic or anaphylactic reaction to any of the substances included in the investigational product: sulfobutylether-β-cyclodextrin, melphalan, bendamustine, chlorambucil or any nitrogen mustard chemotherapeutics.
• Participants who currently use or have an anticipated need for a contraindicated medication including live vaccines, natalizumab, nivolumab, ocrelizumab, palifermin, pimecrolimus, tacrolimus, tofacitinib, and EIAEDs, including phenytoin, phenobarbital, carbamazepine, fosphenytoin, primidone, and oxcarbazepine. The washout period for any live vaccine is 30 days prior to enrollment. There is no restriction for seasonal flu vaccines that do not contain live virus, nor any approved COVID vaccine.
• Participants who are pregnant or breastfeeding.
• Participants who have active medical or psychiatric conditions which, in the opinion of the Principal Investigator or a Sub-Investigator, would compromise or interfere with their ability to participate in the study