Phase 2 Etirinotecan Pegol in Refractory Brain Metastases & Advanced Lung Cancer / Metastatic Breast Cancer

Inclusion Criteria:

   - At least 18 years of age.

   - Life expectancy of 3 months or longer.

   - Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.

Advanced or refractory cancer, consisting of

   - Metastatic breast cancer (mBC) for which single-agent cytotoxic chemotherapy is
   indicated. OR

   - Histologically-proven metastatic lung cancer:

      - Non-small cell lung cancer (NSCLC) as Stage IV disease or recurrent metastatic
      disease [per lung cancer tumor, node and metastasis (TNM) classification system,
      7th ed] (Cohort A) OR

      - Small cell lung cancer (SCLC) as extensive stage or recurrent metastatic disease
      (cohort B), including tumors with mixed small cell and non-small cell elements.

Prior chemotherapy (at least one of the following):

   - At least one line of prior systemic chemotherapy

   - At least one line of prior targeted treatment for metastatic disease Adjuvant systemic
   chemotherapy within prior 6 months Prior treatment for metastatic breast cancer (mBC)
   must have included taxane-based regimen

Prior chemotherapy, including other investigational therapy, has been completed prior to
initiation of study treatment, according to the following:

   - ≥ 2 weeks if immediately preceding treatment was chemotherapy/targeted therapy
   administered on a daily or weekly schedule

   - ≥ 3 weeks if immediately preceding treatment was chemotherapy/targeted therapy
   administered every 2 weeks

   - ≥ 4 weeks if immediately preceding treatment was chemotherapy/targeted therapy
   administered every 3 weeks Previously received at least one CNS directed treatment
   (such as surgery or radiation) OR not be eligible for CNS stereotactic radiosurgery
   Measurable CNS disease, either previously untreated (not counting systemic therapy),
   or progressed following previous radiation treatment. Lesions that have progressed
   after prior radiosurgery should not be selected as measurable disease if they are
   suspected of being radionecrosis.

The following measurement criteria are required, as visualized by contrast-enhanced MRI
with slice thickness of ≤ 1.5 mm, unless absence of contrast or thicker slices is
specifically authorized by Protocol Director. Measurements do not include tumor edema.

   - At least one CNS tumor measuring ≥ 10 mm in longest diameter, OR

   - At least one CNS tumor measuring 5-9 mm in longest diameter, plus one or two
   additional CNS tumors measuring ≥ 3 mm in longest diameter, for which the sum of the
   longest diameters is ≥ 10 mm. Additional tumors are not exclusionary.

Adequate organ function as evidenced by:

   - Absolute neutrophil count (ANC) ≥ 1.5 x 10e9/L without G-CSF (filgrastim,
   pegfilgrastim, or equivalent) support within 7 days

   - Hemoglobin (Hgb) ≥ 9.0 g/dL (90 g/L) without blood transfusion within 7 days

   - Platelet count ≥ 100 x 10e9/L without platelet transfusion within 7 days

   - Bilirubin ≤ 1.5 X upper limit of normal (ULN), except for patients with documented
   history of Gilbert's disease who may have DIRECT bilirubin ≤ 1.5 X ULN

   - Alanine aminotransferase (ALT) ≤ 2.5 X ULN, except ≤ 5 X ULN for patients with liver
   metastases

   - Aspartate aminotransferase (AST) ≤ 2.5 X ULN, except ≤ 5 X ULN for patients with liver
   metastases

   - Serum creatinine ≤ 1.5 X ULN; or calculated creatinine clearance ≥ 50 mL/min (using
   Cockcroft-Gault formula), or measured creatinine clearance ≥ 50 mL/min.

Exclusion Criteria:

   - Previous treatment with a camptothecin derivative (eg, irinotecan, topotecan, and
   investigational agents including but not limited to exatecan, rubitecan, gimatecan,
   karenitecin, SN38 investigational agents, EZN 2208, SN 2310, and AR 67) is not allowed

   - Patients may not have a known history of leptomeningeal disease, as diagnosed by
   positive CSF cytology, unless prospective permission for enrollment is granted from
   the sponsor and the PI

   - Patients may not have had major surgery or radiotherapy (therapeutic and/or
   palliative) within 14 days prior to initiation of study treatment, including
   CNS-directed radiation therapy. Minor procedures, such as tumor biopsy, thoracentesis,
   or intravenous catheter placement are allowed with no waiting period

   - Patients may not have the following co morbid disease or concurrent illness:

      - Chronic or acute gastrointestinal (GI) disorders resulting in diarrhea of any
      severity grade; patients may not use chronic anti-diarrheal supportive care (more
      than 3 days/week) to control diarrhea in the 28 days prior to first dose of
      investigational drug. (exception: anti-diarrheal medications used to control
      symptoms from a medication that will be discontinued prior to study are allowed
      with a 7 day washout before study therapy, for example loperamide for
      erlotinib-associated diarrhea)

      - Known cirrhosis, defined as Child Pugh class A or higher liver disease

      - Other active malignancy, except for non melanoma skin cancer and carcinoma in
      situ (of the cervix or bladder)

      - Any other severe/uncontrolled inter current illness or significant co morbid
      conditions that in the opinion of the investigator would impair study
      participation or cooperation

   - Patients may not have a known allergy or hypersensitivity to any of the components of
   the investigational therapy, including polyethylene glycol (PEG) or topoisomerase
   inhibitors

   - Patients may not be receiving the following medications at the time of first dose of
   investigational drug:

      - Pharmacotherapy for known hepatitis B or C, tuberculosis, or human
      immunodeficiency virus (HIV)

      - Any of the following enzyme inducing anti epileptic medications (EIAEDs):
      phenytoin, carbamazepine, oxcarbazepine, phenobarbital

      - Other chemotherapy, hormonal therapy, immunotherapy, other investigational
      agents, or biologic agents for the treatment of cancer except for bisphosphonates
      or denosumab

   - Pregnant or nursing patients will be excluded from the study