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

Inclusion Criteria:

• 12 years of age or older (*Restrictions apply. Not all therapies are available forpatients <18)

• Histologically-proven locally advanced or metastatic solid tumor, multiple myelomaor B cell non-Hodgkin lymphoma who is no longer benefiting from standard anti-cancertreatment or for whom, in the opinion of the treating physician, no such treatmentis 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 notedabove, drug-specific inclusion/exclusion criteria specified in the protocol appendixfor 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, except in patients with Gilbert's Syndrome

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 withknown hepatic metastases)

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

• Patients must have disease that can be objectively measured by physical orradiographic exam (per RECIST v1.1 for solid tumor, Lugano criteria for non-Hodgkinlymphoma or International Myeloma Working Group criteria for multiple myeloma),defined as at least one lesion that can be accurately measured in at least onedimension (longest diameter to be recorded for non-nodal lesions and short axis fornodal lesions) as ≥20 mm with conventional techniques or as ≥10 mm with spiral CTscan, MRI, or a subcutaneous or superficial lesion that can be measured withcalipers by clinical exam. For lymph nodes, the short axis must be ≥15 mm. Patient'swhose disease cannot be objectively measured by physical or radiographic examination (e.g., elevated serum tumor marker only, bone-only disease without an identifiablesoft tissue component, or patients with only assessable non-measurable disease) areNOT eligible.

• Results must be available from a genomic test or immunohistochemistry (IHC) test forprotein expression performed in a Clinical Laboratory Improvement Amendments (CLIA)-certified and College of American Pathologists (CAP)-accredited or New YorkState accredited (for labs offering services to residents of NY) laboratory. Labsthat have registered the test with the NIH Genetic Testing Registry or that providea report that has been designated as optimized for TAPUR participation arepreferred, but not required. The genomic or IHC test used to qualify a patient forparticipation in TAPUR may have been performed on any specimen of the patient'stumor obtained at any point during the patient's care at the discretion of thepatient's treating physician. Genomic assays performed on cell-free DNA in plasma ("liquid biopsies") will also be acceptable if the genomic analysis is performed ina laboratory that meets the criteria described above.

• Ability to understand and the willingness to sign a written informed consent/assentdocument.

• Have a tumor genomic profile for which single agent treatment with one of the FDAapproved targeted anti-cancer drugs included in this study has potential clinicalbenefit based on the criteria described in protocol.

• For orally administered drugs, the patient must be able to swallow and tolerate oralmedication and must have no known malabsorption syndrome.

• Because of the risks of drug treatment to the developing fetus, women ofchild-bearing potential and men must agree to use adequate contraception (hormonalor barrier method of birth control; abstinence) for the duration of studyparticipation, and for four months following completion of study therapy. Should awoman become pregnant or suspect she is pregnant while participating in this studyor if she is the partner of a male participant in this study and becomes pregnantwhile he is participating in this study, she should inform her or her partner'streating physician immediately as well as her obstetrician. Female study patientswho become pregnant must immediately discontinue treatment with any study therapy.Male patients should avoid impregnating a female partner. Male study patients, evenif surgically sterilized, (i.e. post-vasectomy) must agree to one of the following:practice effective barrier contraception during the entire study treatment periodand for a specified amount of time the last dose of study drug, or completelyabstain 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 radiographicimaging or physical examination (e.g., elevated serum tumor marker only) are noteligible

• Patients with primary brain tumors or leptomeningeal metastases are excluded.

• Patients with previously treated brain metastases are eligible, provided that thepatient has not experienced a seizure or had a clinically significant change inneurological status within the 3 months prior to registration. All patients withpreviously treated brain metastases must be clinically stable for at least 1 monthafter completion of treatment and off steroid treatment for one month prior to studyenrollment.

• Patients with known progressive brain metastases are eligible but additionaleligibility criteria apply.

Note: there are additional exclusion criteria that may apply