Targeted Therapy Directed by Genetic Testing in Treating Patients With Advanced Refractory Solid Tumors, Lymphomas, or Multiple Myeloma (The MATCH Screening Trial)

PRIMARY OBJECTIVES:

I. To evaluate the proportion of patients with objective response (OR) to targeted study
agent(s) in patients with advanced refractory cancers/lymphomas/multiple myeloma.

SECONDARY OBJECTIVES:

I. To evaluate the proportion of patients alive and progression free at 6 months of treatment
with targeted study agent in patients with advanced refractory cancers/lymphomas/multiple
myeloma.

II. To evaluate time until death or disease progression. III. To identify potential
predictive biomarkers beyond the genomic alteration by which treatment is assigned or
resistance mechanisms using additional genomic, ribonucleic acid (RNA), protein and
imaging-based assessment platforms.

IV. To assess whether radiomic phenotypes obtained from pre-treatment imaging and changes
from pre- through post-therapy imaging can predict objective response and progression free
survival and to evaluate the association between pre-treatment radiomic phenotypes and
targeted gene mutation patterns of tumor biopsy specimens.

OUTLINE:

STEP 0 (Screening): Patients undergo biopsy along with molecular characterization of the
biopsy material for specific, pre-defined mutations, amplifications, or translocations of
interest via tumor sequencing and immunohistochemistry. Consenting patients also undergo
collection of blood samples for research purposes.

STEPS 1, 3, 5, 7 (Treatment): Patients are assigned to 1 of 35 treatment subprotocols based
on molecularly-defined subgroup. (See Arms Section)

STEPS 2, 4, 6 (Screening): Patients experiencing disease progression on the prior Step
treatment or who could not tolerate the assigned treatment undergo review of their previous
biopsy results to determine if another treatment is available or undergo another biopsy.
Patients may have a maximum of 2 screening biopsies and 2 treatments per biopsy.

STEP 8 (Optional Research): Consenting patients undergo end-of-treatment biopsy and
collection of blood samples for research purposes.

After completion of study treatment, patients are followed up every 3 months for 2 years and
then every 6 months for 1 year.

Inclusion Criteria:

- ELIGIBILITY CRITERIA FOR SCREENING BIOPSY (STEP 0)

- Women of childbearing potential must have a negative serum pregnancy test within 2
weeks prior to registration; patients that are pregnant or breast feeding are
excluded; a female of childbearing potential is any woman, regardless of sexual
orientation or whether they have undergone tubal ligation, who meets the following
criteria:

- Has not undergone a hysterectomy or bilateral oophorectomy; or

- Has not been naturally postmenopausal for at least 24 consecutive months (i.e.,
has had menses at any time in the preceding 24 consecutive months)

- Women of childbearing potential and men must agree to use adequate contraception
(hormonal or barrier method of birth control; abstinence) prior to study entry, for
the duration of study participation, and for 4 months after completion of study;
should a woman become pregnant or suspect while she or her partner is participating in
this study, she should inform her treating physician immediately

- Patients must have histologically documented solid tumors or histologically confirmed
diagnosis of lymphoma or multiple myeloma requiring therapy and meet one of the
following criteria:

- Patients must have progressed following at least one line of standard systemic
therapy and there must not be other approval/standard therapy available that has
been shown to prolong overall survival (i.e. in a randomized trial against
another standard treatment or by comparison to historical controls); patients who
cannot receive other standard therapy that has been shown to prolong overall
survival due to medical issues will be eligible, if other eligibility criteria
are met; if the patient is currently receiving therapy, the clinician must have
assessed that the current therapy is no longer benefitting the patient prior to
enrolling on MATCH, regardless of whether it is considered standard OR

- Patients for whose disease no standard treatment exists that has been shown to
prolong overall survival

- NOTE: No other prior malignancy is allowed except for the following: adequately
treated basal cell or squamous cell skin cancer; in situ cervical cancer;
adequately treated stage I or II cancer from which the patient is currently in
complete remission; any other cancer from which the patient has been disease-free
for 5 years

- Patients must have measurable disease

- Patients must meet the criteria below and have received results from one of the
designated outside laboratories indicating a "rare variant" that is an actionable
Mutation of Interest (aMOI) for specific select subprotocols.

- The following requirements apply:

- The outside laboratory specifically notified the site that patient may be a
potential candidate for MATCH due to a detected "rare variant"; the outside
lab reports are NOT sufficient for this purpose

- NOTE: The content and format of these specific notifications for the
Outside Assay process will vary depending on the designated outside lab
in question, as they are each responsible for their own outreach
efforts; it is strongly recommended that the designated outside
laboratory be contacted to confirm the format and receipt of this
notification prior to registering any patients to Step 0

- Patients with an applicable "rare variant" must be able to meet the
eligibility criteria for the appropriate subprotocols within 4 weeks
following notification of treatment assignment

- NOTE: The receipt of this notification (and the start of the associated
deadline for Step 1 registration) may occur shortly after Step 0
registration, since these patients will not be submitting tissue for
screening purposes; however, for certain "rare variant" arms,
submission of archival tissue for central immunohistochemistry (IHC)
testing may be required

- Registration to Step 0 must occur after stopping prior systemic anti-cancer
therapy; there is no specific duration for which patients must be off
treatment prior to registration to Step 0, as long as all eligibility
criteria are met

- There is no particular window of time after notification of potential
eligibility from an outside lab in which the patient must be registered to
Step 0, but treatment slots will be assigned on a first come, first serve
basis to those who do register to Step 0, and are not held for those
notified of potential eligibility who do not register to Step 0

- Patients may have received other non-targeted, immunotherapy or targeted
treatment between the prior genetic testing at the outside lab and
registration to Step 0; the decision to stop such treatment in favor of
participation in MATCH, if no further clinical benefit is expected, is per
the treating physician's discretion; documentation of a lack of response to
the prior treatment is not required in these cases

- NOTE: Other potential aMOIs that would be eligibility criteria for "NON
RARE" arms, as determined by the designated laboratories, are not
applicable for this process in MATCH

- NOTE: Tumor tissue for the confirmation of "rare variant" by the MATCH
assay is to be submitted, preferably from the same time of collection
as that evaluated by the designated outside laboratory

- Patient must not require the use of full dose coumarin-derivative anticoagulants such
as warfarin; low molecular weight heparin is permitted for prophylactic or therapeutic
use; factor X inhibitors are permitted

- NOTE: Warfarin may not be started while enrolled in the EAY131 study

- Stopping the anticoagulation for biopsy should be per site standard operating
procedure (SOP)

- Patients must have Eastern Cooperative Oncology Group (ECOG) performance status =< 1
and a life expectancy of at least 3 months

- Patients must not currently be receiving any other investigational agents

- Patients must not have any uncontrolled intercurrent illness including, but not
limited to:

- Symptomatic congestive heart failure (New York Heart Association [NYHA]
classification of III/IV)

- Unstable angina pectoris or coronary angioplasty, or stenting within 6 months
prior to registration to Step 0, 2, 4, 6

- Cardiac arrhythmia (ongoing cardiac dysrhythmias of National Cancer Institute
[NCI] Common Terminology Criteria for Adverse Events [CTCAE] version [v]4 grade
>= 2)

- Psychiatric illness/social situations that would limit compliance with study
requirements

- Intra-cardiac defibrillators

- Known cardiac metastases

- Abnormal cardiac valve morphology (>= grade 2) documented by echocardiogram
(ECHO) (as clinically indicated); (subjects with grade 1 abnormalities [i.e.,
mild regurgitation/stenosis] can be entered on study); subjects with moderate
valvular thickening should not be entered on study

- NOTE: To receive an agent, patient must not have any uncontrolled intercurrent
illness such as ongoing or active infection; patients with infections unlikely to
be resolved within 2 weeks following screening should not be considered for the
trial

- Patients must be able to swallow tablets or capsules; a patient with any
gastrointestinal disease that would impair ability to swallow, retain, or absorb drug
is not eligible

- Patients who are human immunodeficiency virus (HIV)-positive are eligible if:

- CD4+ cell count greater or equal to 250 cells/mm^3

- If patient is on antiretroviral therapy, there must be minimal interactions or
overlapping toxicity of the antiretroviral therapy with the experimental cancer
treatment; for experimental cancer therapeutics with CYP3A/4 interactions,
protease inhibitor therapy is disallowed; suggested regimens to replace protease
inhibitor therapy include dolutegravir given with tenofovir/emtricitabine;
raltegravir given with tenofovir and emtricitabine; once daily combinations that
use pharmacologic boosters may not be used

- No history of non-malignancy acquired immune deficiency syndrome (AIDS)-defining
conditions other than historical low CD4+ cell counts

- Probable long-term survival with HIV if cancer were not present

- Any prior therapy, radiotherapy (except palliative radiation therapy of 30 gray [Gy]
or less), or major surgery must have been completed >= 4 weeks prior to start of
treatment; all adverse events due to prior therapy have resolved to a grade 1 or
better (except alopecia and lymphopenia) by start of treatment; palliative radiation
therapy must have been completed at least 2 weeks prior to start of treatment; the
radiotherapy must not be to a lesion that is included as measurable disease

- NOTE: Prostate cancer patients may continue their luteinizing hormone-releasing
hormone (LHRH) agonist

- NOTE: For patients entering the study via the original screening process,
patients may receive non-protocol treatment after biopsy (if clinically
indicated) until they receive notification of results; however, lack of response
must be documented prior to registration to Step 1; new non-protocol treatment
will NOT be permitted as intervening therapy after registration to Step 0; the
only intervening treatment permitted is prior therapy that the patient already
received prior to Step 0 registration; the decision to stop the intervening
non-protocol treatment will be left up to the treating physician if patient has
an aMOI; however, patients will need to be off such therapy for at least 4 weeks
before receiving any MATCH protocol treatment

- NOTE: For patients entering the study via a designated outside laboratory, no
intervening systemic non-protocol treatment is permitted after Step 0
registration; all other eligibility requirements still apply to these patients,
including the washouts for prior therapy noted above in this section, the time
restrictions outlined, and the eligibility criteria for the intended subprotocol

- Patients with brain metastases or primary brain tumors must have completed treatment,
surgery or radiation therapy >= 4 weeks prior to start of treatment

- Patients must have discontinued steroids >= 1 week prior to registration to Step 0 and
remain off steroids thereafter, except as permitted (see below); patients with
glioblastoma (GBM) must have been on stable dose of steroids, or be off steroids, for
one week prior to registration to treatment (Step 1, 3, 5, 7)

- NOTE: The following steroids are permitted (low dose steroid use is defined as
prednisone 10 mg daily or less, or bioequivalent dose of other corticosteroid):

- Temporary steroid use: e.g. for computed tomography (CT) imaging in setting
of contrast allergy

- Low dose steroid use for appetite

- Chronic inhaled steroid use

- Steroid injections for joint disease

- Stable dose of replacement steroid for adrenal insufficiency or low doses
for non-malignant disease

- Topical steroid

- Steroids required to manage toxicity related to study treatment, as
described in the subprotocols

- Steroids required as pre- or post-chemotherapy medication for acceptable
intervening chemotherapy

- NOTE: Steroids must be completed alongside last dose of chemotherapy

- Leukocytes >= 3,000/mcL (within 2 weeks prior to screening step registration and
within 4 weeks prior to treatment step registration)

- Absolute neutrophil count >= 1,500/mcL (within 2 weeks prior to screening step
registration and within 4 weeks prior to treatment step registration)

- Platelets >= 100,000/mcL (within 2 weeks prior to screening step registration and
within 4 weeks prior to treatment step registration)

- NOTE: Patients with documented bone marrow involvement by lymphoma are not required to
meet the above hematologic parameters, but must have a platelet count of at least
75,000/mcL and neutrophil count of at least 1,000/mcL

- Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) (unless documented
Gilbert's syndrome, for which bilirubin =< 3 x institutional ULN is permitted) (within
2 weeks prior to screening step registration and within 4 weeks prior to treatment
step registration)

- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
=< 2.5 x institutional ULN (up to 5 times ULN in presence of liver metastases) (within
2 weeks prior to screening step registration and within 4 weeks prior to treatment
step registration)

- Creatinine clearance >= 45 mL/min/1.73 m^2 for patients with creatinine levels above
institutional normal

- As defined by the Cockcroft-Gault equation (within 2 weeks prior to screening
step registration and within 4 weeks prior to treatment step registration)

- Patients must have an electrocardiogram (ECG) within 8 weeks prior to registration to
screening step and must meet the following cardiac criteria:

- Resting corrected QT interval (QTc) =< 480 msec

- NOTE: If the first recorded QTc exceeds 480 msec, two additional,
consecutive ECGs are required and must result in a mean resting QTc =< 480
msec; it is recommended that there are 10-minute (+/- 5 minutes) breaks
between the ECGs

- The following only need to be assessed if the mean QTc > 480 msec

- Check potassium and magnesium serum levels

- Correct any identified hypokalemia and/or hypomagnesemia and may repeat ECG
to confirm exclusion of patient due to QTc

- For patients with heart rate (HR) 60-100 beats per minute (bpm), no manual
read of QTc is required

- For patients with baseline HR < 60 or > 100 bpm, manual read of QT by
trained personnel is required, with Fridericia correction applied to
determine QTc

- Patient must not have hypokalemia (value < institutional lower limit of
normal)

- No factors that increase the risk of QTc prolongation or risk of arrhythmic
events such as heart failure, congenital long QT syndrome, family history of long
QT syndrome or unexplained sudden death under 40 years of age or any concomitant
medication known to prolong the QT interval

- NOTE: Patient must be taken off prohibited medication prior to registration
to the screening step (Step 0, 2, 4, 6) and remain off these medications
thereafter, unless permitted on a subprotocol for the management of
treatment related toxicity; patient must be off the drug for at least 5
half-lives prior to registration to the treatment step (Step 1, 3, 5, 7);
the medication half-life can be found in the package insert for Food and
Drug Administration (FDA) approved drugs

- ELIGIBILITY CRITERIA FOR FIRST TREATMENT (STEP 1)

- If patients have been biopsied or submitted archived tumor tissue obtained within the
last 6 months for assessment with the MATCH assays, patients may receive non-protocol
treatment after biopsy/tissue submission (if clinically indicated) until they receive
notification of results however, lack of response must be documented prior to
registration to step 1; new non-protocol treatment will NOT be permitted as
intervening therapy after registration to Step 0; for pat