TAPUR: Testing the Use of Food and Drug Administration (FDA) Approved Drugs That Target a Specific Abnormality in a Tumor Gene in People With Advanced Stage Cancer

The Targeted Agent and Profiling Utilization Registry (TAPUR) Study is a non-randomized
clinical trial that aims to describe the safety and efficacy of commercially available,
targeted anticancer drugs prescribed for treatment of patients with advanced cancer that has
a potentially actionable genomic variant. TAPUR will study Food and Drug Administration
(FDA)-approved targeted therapies that are contributed by collaborating pharmaceutical
companies, catalogue the choice of molecular profiling test by clinical oncologists and
develop hypotheses for additional clinical trials.

Inclusion Criteria:

- 12 years of age or older (*Restrictions apply. Not all therapies are available for
patients <18)

- Histologically-proven locally advanced or metastatic solid tumor, multiple myeloma or
B cell non-Hodgkin lymphoma who is no longer benefiting from standard anti-cancer
treatment or for whom, in the opinion of the treating physician, no such treatment is
available or indicated

- Performance status 0-2 (Per Eastern Cooperative Oncology Group (ECOG) criteria)

- Patients must have acceptable organ function as defined below. However, as noted
above, drug-specific inclusion/exclusion criteria specified in the protocol appendix
for each agent will take precedence for this and all inclusion criteria:

1. Absolute neutrophil count ≥ 1.5 x 106/µl

2. Hemoglobin > 9.0 g/dl

3. Platelets > 75,000/µl

4. Total bilirubin < 2.0 mg/ dl

5. Aspartate aminotransferase (AST) serum glutamic-oxaloacetic transaminase (SGOT)
and alanine aminotransferase (ALT) serum glutamic-pyruvic transaminase (SGPT) <
2.5 x institutional upper limit of normal (ULN) (or < 5 x ULN in patients with
known hepatic metastases)

6. Serum creatinine ≤ 1.5 × ULN or calculated or measured creatinine clearance ≥ 50
mL/min/1.73 m2

- Patients must have measurable or evaluable disease (per RECIST v1.1 for solid tumor,
Lugano criteria for non Hodgkin lymphoma or International Myeloma Working Group
criteria for multiple myeloma), defined, as at least one lesion that can be accurately
measured in at least one dimension (longest diameter to be recorded for non-nodal
lesions and short axis for nodal lesions) as ≥20 mm with conventional techniques or as
≥10 mm with spiral computed tomography (CT) scan, Magnetic Resonance Imaging (MRI), or
a subcutaneous or superficial lesion that can be measured with calipers by clinical
exam. For lymph nodes, the short axis must be ≥15 mm. Patients who have assessable
disease by physical or radiographic examination but do not meet these definitions of
measurable disease are eligible and will be considered to have evaluable disease.
Patient's whose disease cannot be objectively measured by physical or radiographic
examination (e.g., elevated serum tumor marker only) are NOT eligible

- Results must be available from a genomic test or immunohistochemistry (IHC) test for
protein expression performed in a Clinical Laboratory Improvement Amendments
(CLIA)-certified, College of American Pathologists (CAP) -accredited, New York State
accredited (for labs offering services to residents of NY) laboratory that has
registered the test with the National Institutes of Health (NIH) Genetic Test Registry
or has established an integration with the TAPUR platform. The genomic or IHC test
used to qualify a patient for participation in TAPUR may have been performed on any
specimen of the patient's tumor obtained at any point during the patient's care at the
discretion of the patient's treating physician. Genomic assays performed on cell-free
DNA in plasma ("liquid biopsies") will also be acceptable if the genomic analysis is
performed in a laboratory that meets the criteria described above.

- Ability to understand and the willingness to sign a written informed consent/assent
document

- Have a tumor genomic profile for which single agent treatment with one of the FDA
approved targeted anti-cancer drugs included in this study has potential clinical
benefit based on the criteria described in protocol

- For orally administered drugs, the patient must be able to swallow and tolerate oral
medication and must have no known malabsorption syndrome

- Because of the risks of drug treatment to the developing fetus, women of child-bearing
potential and men must agree to use adequate contraception (hormonal or barrier method
of birth control; abstinence) for the duration of study participation, and for four
months following completion of study therapy. Should a woman become pregnant or
suspect she is pregnant while participating in this study or if she is the partner of
a male participant in this study and becomes pregnant while he is participating in
this study, she should inform her or her partner's treating physician immediately as
well as her obstetrician. Female study patients who become pregnant must immediately
discontinue treatment with any study therapy. Male patients should avoid impregnating
a female partner. Male study patients, even if surgically sterilized, (i.e.
post-vasectomy) must agree to one of the following: practice effective barrier
contraception during the entire study treatment period and through 4 months after the
last dose of study drug, or completely abstain from sexual intercourse

Note: TAPUR does not explicitly exclude any type of solid tumor, but the patient must have
measurable and evaluable disease per RECIST v1.1

Exclusion Criteria:

- Patients whose disease is not measurable or cannot be assessed by radiographic imaging
or physical examination (e.g., elevated serum tumor marker only) are not eligible

- Patients with primary brain tumors are excluded. Patients with known progressive brain
metastases determined by serial imaging or declining neurologic function in the
opinion of the treating physician are not eligible. Patients with previously treated
brain metastases are eligible, provided that the patient has not experienced a seizure
or had a clinically significant change in neurological status within the 3 months
prior to registration. All patients with previously treated brain metastases must be
clinically stable for at least 1 month after completion of treatment and off steroid
treatment for one month prior to study enrollment.

Note: there are additional exclusion criteria that may apply