Genetically-informed Therapies for Patients With Metastatic Cancer

Treatment with a personalized targeted therapy plan based on cancer genetics will improve
time to disease progression (TTP) compared to standard therapies.

By comparing A) a patient's TTP on targeted therapy vs. B) their TTP on their most recent
prior therapy, investigators will minimize the variability in TTP observed across cancer
subtypes, and be able to enroll patients with any type of solid tumor in a statistically
unbiased manner. Based on the literature, investigators expect at least 35% of patients
treated with a genetically-informed targeted therapy to exhibit a longer progression-free
interval than would be expected with standard therapies. This "TTP ratio" for each patient
is calculated using the formula:

TTP ratio: (TTP on targeted therapy) / (TTP on most recent non-targeted therapy)

An individual patient's benefit from genetically-informed targeted therapy is defined as a
TTP ratio ≥ 1.3

Inclusion Criteria:

- Histologically confirmed metastatic cancer that has progressed by RECIST criteria on
at least 1 prior therapy in the metastatic setting.

- Patients must have not received anti-cancer therapy (i.e., EGFR, BRAF, AR, ER or Her2
targeted agents , chemotherapy, radiation or surgery) within the last 4 weeks, and
must have recovered to Grade 2 or better from all treatment-related adverse events.

- Karnofsky performance status ≥ 60%

- Women should not be lactating or pregnant. If of childbearing age, she must have a
negative pregnancy test within two weeks of entry to the study and practice effective
birth control during the study.

- Patient must be mentally competent and provide written informed consent for study
participation.

- Tumor tissue must be obtained through a clinically indicated biopsy or
surgical procedure, performed as standard-of-care for progression of disease.

- Patient must consent to the use of blood, plasma, and tumor tissues for research
purposes. Only tumor genetic information will be used to recommend therapy in this
study. Tumor, blood and/ or plasma may be retrospectively analyzed for
research purposes.

- Patients must be willing to consent to paying for the supply of drug if necessary.
Cost estimates will be provided at the time of consent. As per the current standard
of care for prescription drugs, the treating oncologist and his/her staff will be
responsible for making every effort to obtain reimbursement and/or find the lowest
possible cost of drug to minimize out of pocket costs.

Exclusion Criteria:

- Concomitant second invasive malignancy within five years of enrollment except for
non- melanoma skin cancer.

- In patients with a prior history of invasive malignancy, less than five years in
complete remission.

- Evidence of significant comorbidities such as uncontrolled diabetes, hypertension
or active infection that would preclude treatment on a proposed regimen.

- Prior treatment with proposed regimen.

- Clinically significant gastrointestinal abnormalities including but not limited to
malabsorption syndrome, major resection of stomach or small bowel affecting
absorption of oral drugs, active peptic ulcer disease, inflammatory bowel disease,
history of small bowel obstruction abscess or fistula within 28 days prior to
beginning study treatment.

- Presence of uncontrolled infection.

- Known lesion infiltrating major vessels, with risk of bleeding or perforation, as
determined by radiographic review.

- Any serious and/or unstable pre-existing medical, psychiatric, or other conditions
that could interfere with subject's safety, obtaining informed consent or compliance
to the study.

- Any ongoing toxicity from prior anti-cancer therapy that is Grade 3 or higher and /or
progressing in severity.

- Untreated brain metastasis that have progressed within the 8-week period prior to
enrollment.