Pharmacodynamic Biomarkers of Standard Anti-microtubule Drugs as Assessed by Early Tumor Biopsy

During the screening visit, the following will be taken: medical history; physical exam; ECOG
performance status; a pregnancy test if indicated per physician (confirmation of the clinical
testing result or assessment of the treating physician whether or not the subject is capable
of pregnancy); AST, ALT, CBC (per oncologist); 15 mL blood sample for drug level assessment;
15 mL blood sample for circulating tumor DNA (ctDNA); follow up assessments of cancer; RECIST
1.1 response measurements; and an archived FFPE sample (8 slides) will be obtained.

While enrolled on study, subjects will have the following procedures:

- 15 mL blood sample for drug level assessment on C1D2

- 15 mL blood sample for circulating tumor DNA (ctDNA) on C1D2 and at progression or end
of study for a total of 30 mL

- Adverse events related to study procedures (research biopsy & blood draws) will be
assessed on C1D2 and at progression or end of study

- Toxicity evaluations will occur throughout the study per the treating MD

- Follow-up assessments of cancer will occur throughout the study per the treating MD

- RECIST 1.1 response measurements will be taken at standard of care imaging

- Fresh biopsy or tumor sampling (4 cores) for analysis of intratumoral drug levels and
biomarkers including: markers of proliferation (mitotic index), aneuploidy, and
sequencing analysis (ctDNA) on C1D2.

The tests being performed on the samples as part of this study are not investigational.

Subjects will be followed with imaging scans and tumor markers as deemed appropriate by the
treating physician. Follow-up scans will be recommended every ~3 cycles as per standard of
care. Subjects will be followed for the duration of treatment initiated while taking part in
this study. Follow-up will discontinue either 2 months following completion of planned breast
cancer treatment or upon the systemic imaging following therapy completion (whichever is
later).

Inclusion Criteria:

- Men and women with histologically or cytologically demonstrated breast cancer that is
deemed metastatic or incurable by the treating physician.

- It is medically appropriate to treat the patient with an antimitotic agent or an
intravenous control chemotherapeutic agent by IV infusion at standard doses as per the
treating physician. Please see NCCN guidelines for standard of care, p58 for standard
chemotherapy regimens for recurrent or metastatic breast cancer7.

- The patient has measureable disease as determined by RECIST 1.1.

- Archived tissue is available from either primary, metastatic site or both.

- It is safe and feasible to obtain a research tumor biopsy on cycle 1 day 2 with a
biopsy of an accessible lesion such as liver, lung, lymph node, skin, breast, or bone.

- All pre-chemotherapy test results (tests per treating oncologist discretion) have been
reviewed and deemed appropriate for planned chemotherapy by the patient's treating
oncologist.

Exclusion Criteria:

- HER2+ breast cancer by standard criteria.

- Pregnant women are excluded from this study because systemic chemotherapy may cause
deleterious effects to the fetus. Because there is an unknown but potential risk for
adverse events in nursing infants secondary to treatment of the mother with systemic
chemotherapy, breastfeeding should be discontinued if the mother is enrolled in the
trial.

- Planned treatment with hormonal therapy, or targeted oral therapy during trial
enrollment.