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

Trial end date:
Target enrollment:
Participant gender:
This phase II MATCH trial studies how well treatment that is directed by genetic testing works in patients with solid tumors or lymphomas that have progressed following at least one line of standard treatment or for which no agreed upon treatment approach exists. Genetic tests look at the unique genetic material (genes) of patients' tumor cells. Patients with genetic abnormalities (such as mutations, amplifications, or translocations) may benefit more from treatment which targets their tumor's particular genetic abnormality. Identifying these genetic abnormalities first may help doctors plan better treatment for patients with solid tumors, lymphomas, or multiple myeloma.
Phase 2
Accepts Healthy Volunteers?
Lead Sponsor:
National Cancer Institute (NCI)
Ado-Trastuzumab Emtansine
Antibodies, Monoclonal
Antineoplastic Agents, Immunological
Immunoglobulin G
Trastuzumab biosimilar HLX02
Inclusion Criteria:


- Patients 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 patient of childbearing potential is anyone, regardless of sexual
orientation or whether they have undergone tubal ligation, who meets the following

- Has achieved menarche at some point

- 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)

- Patients must not expect to conceive or father children by using accepted and
effective method(s) of contraception or by abstaining from sexual intercourse prior to
study entry, for the duration of study participation, and for 4 months after
completion of study; should a patient or partner of the patient become pregnant or
suspect a pregnancy while participating in this study, the treating physician should
be informed 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

- 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 used to determine
patient candidacy for treatment arm assignment

- 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

- 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

- 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

- Patient meets one of the following criteria:

- Patient is a candidate for Z1M based on local CLIA assessment of MMRd
by immunohistochemistry (IHC) or MSI status by polymerase chain
reaction (PCR), adequate tumor tissue is available for submission for
mandatory central screening IHC and the patient will be able to meet
the eligibility criteria for Z1M within 4 weeks following notification
of treatment assignment OR

- The sites 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

- NOTE: There is no particular window of time after receiving the sequencing report
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

- NOTE: Treatment assignment (and the start of the associated deadline for Step 1
registration) may occur shortly after Step 0 registration. Note that certain
"rare variant" arms require submission of archival tissue for central IHC testing
to determine treatment assignment. For those arms, adequate tissue for the
central IHC is required to be available for submission

- 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

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

- 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; 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 (ANC) >= 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 ULN

- 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

- 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


- NOTE: For patients entering step 0 with assay results from outside laboratories, no
systemic treatment is allowed after step 0 registration

- As MATCH is designed to add additional subprotocols, implement limited expansions of
accrual for certain subprotocols, and/or amend existing arm-specific eligibility
criteria, some patients entering under the original screening method may be eligible
to have their results rerun in MATCHbox, even if they did not match to a treatment
initially or did not receive a treatment assignment due to a lack of available
assignment slots; patients whose sequence results will be rerun through MATCHbox must
also meet the following criteria:

- Samples must have been collected within 5 months of the activation of the
addendum, as there is an additional month needed to get the patients on trial

- Patient has not had treatment within the 5 months that resulted in a PR or better
after the performance of the screening assessment

- Patient must meet eligibility criteria, including performance status 1 or better
and life expectancy of at least 3 months

- Patients must meet the eligibility requirements with the following exceptions:

- Patients may have received other non-targeted, immunotherapy or targeted
treatment, which could be stopped in favor of returning to MATCH, if no
response to the interim treatment has occurred and no further benefit is
expected from this interim treatment, per the treating physician's
discretion; documentation of a lack of response to the interim treatment is
not required in these cases; however, the following restrictions apply:

- Enrollment onto another investigational therapeutic study is not

- Patient cannot be responding to interim treatment, since the benefit of
the MATCH treatment is unknown and may deprive patient of an effective
treatment if it were given when a patient is responding to another

- NOTE: Patients meeting these criteria will NOT be biopsied at this time point;
instead, their step 0 results will be re-interrogated to determine if another
treatment is available


- Patient's disease