Study Assessing QBS72S For Treating Brain Metastases

Inclusion Criteria:

   1. The participant must be 18 years or older

   2. The participant must have a Karnofsky Performance Status (KPS) of 60 or above.

   3. One of the following:

      1. Cohorts 1 and 2: The participant must have a histologically-confirmed breast
      cancer primary tumor, either confirmed via primary specimen or via metastasis
      site, having developed brain metastases (parenchymal or LMD) after a prior
      cytotoxic chemotherapy regimen.

      2. Cohort 3: The participant must have a histologically cancerous primary tumor,
      either confirmed via primary specimen or via metastasis site, having developed
      brain metastases (parenchymal or LMD) after a prior cytotoxic chemotherapy
      regimen. There is no restriction on prior cycles of systemic therapy for any
      primary cancer type. Breast cancer is not excluded from Cohort 3.

   4. One of the following:

      1. Cohort 1: A participant with breast cancer brain parenchymal tumors must have at
      least one nonirradiated tumor ≥ 3 mm2 that can be seen on 2 or more separate
      acquired brain MRI sequences.

      2. Cohort 2: A participant with breast cancer primary and

   LMD must receive either:

   i. a brain MRI with contrast that supports the presence of LMD, or ii. a CSF cytology
   test that is either positive for or suspicious for malignancy. The presence of
   parenchymal brain metastases does not exclude these participants from Cohort 2.

   a. Cohort 3: A participant with LMD from any primary cancer site must receive either:
   i. a brain MRI with contrast that supports the presence of LMD, or ii. a CSF cytology
   test that is either positive for or suspicious for malignancy. The presence of
   parenchymal brain metastases does not exclude these participants from Cohort 3.

   5. For corticosteroids and anticonvulsants, the participant must either: c. not be taking
   any, or d. be taking stable or decreasing doses for ≥5 days prior to obtaining the
   screening Gd-MRI of the brain. The maximum allowable dose of corticosteroids is 8mg of
   dexamethasone per day, or the equivalent of another medication as assessed by a
   Neuro-Oncologist. Escalation of corticosteroids is not allowed ≤14 days prior to C1D1.

   6. The participant must have completed washout from prior therapy before C1D1, as
   applicable: e. ≥7 days for Ommaya placement (Cohorts 2+3) f. ≥14 days for small
   molecules and non-cytotoxic systemic drugs e.g., PARP inhibitors g. ≥21 days for
   checkpoint inhibitors and monoclonal antibodies, e.g., atezolizumab, pembrolizumab,
   and bevacizumab, and cytotoxic chemotherapy h. ≥28 days for investigational drugs,
   radiotherapy, and major surgery. Minor procedures such as tumor biopsy are allowed
   with written approval from the PI i. ≥1 dosing cycle for other interventions All
   significant toxicities from previous anticancer therapy must have stabilized to a new
   baseline or have resolved. Participation in long term follow up in another clinical
   trial is allowed if no procedures will be performed which may interfere with the
   interpretation of study results.

   7. The participant must have adequate bone marrow function, including: j. ANC ≥ 1,500/mm3
   or ≥ 1.5 x 109/L k. Platelets ≥ 100,000/ mm3 or ≥ 100 x 109/L l. Hemoglobin ≥ 9 g/dL

   8. 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.

   9. The participant must have adequate liver function, including: m. Total serum bilirubin
   ≤ 1.5 x ULN unless the participant has documented Gilbert syndrome who must have a
   total bilirubin < 3.0 mg/dl n. Aspartate and Alanine aminotransferase (AST and ALT) ≤
   2.5 x ULN; ≤ 5.0 x ULN if there is liver involvement by the tumor

10. 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.

11. 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

   1. Participants with any other current, active malignancy unrelated to their primary
   cancer diagnosis, except for adequately treated basal cell or squamous cell skin
   cancer or carcinoma in situ.

   2. 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.

   3. 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.

   4. Participants who are pregnant or breastfeeding.

   5. 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.