NCT02465060 · CITED IN SOURCE DOCUMENTS

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

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase: PHASE2
Status at capture: ACTIVE NOT RECRUITING
Registry last update: 2026-08-28

This phase II MATCH screening and multi-sub-trial studies how well treatment that is directed by genetic testing works in patients with solid tumors, lymphomas, or multiple myelomas that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) and does not respond to treatment (refractory). Patients must 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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

No posted result sections were captured. Registered plans do not establish that a treatment works.

Who could take part

eligibility Criteria: Inclusion Criteria: * ELIGIBILITY CRITERIA FOR SCREENING BIOPSY (STEP 0) * Patients must be \>= 18 years of age. Because no dosing or adverse event data are currently available on the use of study investigational agents in patients \< 18 years of age, children are excluded from this study * 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 whether they have undergone tubal ligation, who meets the following criteria: * 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 Clinical Laboratory Improvement Act (CLIA) assessment of mismatch repair deficiency (MMRd) by immunohistochemistry (IHC) or microsatellite instability (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 * 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; 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 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 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) * 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 permitted * 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 treatment * 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 * ELIGIBILITY CRITERIA FOR SECOND SCREENING (STEP 2) * Patient's disease has progressed on Step 1 treatment or patient could not tolerate assigned treatment * NOTE: PATIENTS ENTERING STEP 1 WITH A "RARE VARIANT" FROM AN "OUTSIDE" LAB ARE NOT ELIGIBLE FOR STEP 2 * No response and progression (or inability to tolerate further treatment) occurred \< 6 months from start of step 1 treatment * NOTE: Patients meeting these criteria will NOT be biopsied at this time point; instead, their step 0 MATCH assay results will be re-interrogated to determine if another treatment is available upon registration to this study step; it is not necessary to confirm the availability of another potential treatment assignment in advance; only aMOIs detected by the MATCH assay may be used for the determination of eligibility to a relevant subprotocol OR * Progression (or inability to tolerate further treatment) occurred after a (1) response OR (2) after \>= 6 months from start of step 1 treatment; patient must have tumor amenable to percutaneous biopsy and be willing and able to undergo a tumor biopsy or bone marrow aspirate for collection and submission of tumor tissue OR patient will be undergoing a procedure due to medical necessity during which the tissue may be collected for the central determination of the presence of one or more of the specific "actionable" mutations/amplifications of interest (aMOI); archived specimens cannot be accepted * Patients must meet eligibility criteria as defined in step 0 * Patient must not have been assigned to step 1 treatment based on a "rare variant" determined by a designated outside laboratory * ELIGIBILITY CRITERIA FOR SECOND TREATMENT (STEP 3) * NOTE: If screening biopsy samples were submitted during step 2, 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 3; new non-protocol treatment will NOT be permitted as intervening therapy after registration to step 2; the decision to stop the intervening nonprotocol treatment will be left up to the treating physician if patient has an aMOI; waiting periods as described will apply * ELIGIBILITY CRITERIA FOR THIRD SCREENING (STEP 4) * Patient's disease has progressed on step 3 treatment or patient could not tolerate assigned treatment * Patient must meet one of the following criteria: * No response and progression (or inability to tolerate further treatment) occurred \< 6 months from start of step 3 (second) treatment AND a biopsy was performed at step 2 screening * NOTE: Patients meeting these criteria will NOT be biopsied at this time point; instead, their latest MATCH assay results will be re-interrogated to determine if another treatment is available upon registration to this study step; it is not necessary to confirm the availability of another potential treatment assignment in advance OR * Progression (or inability to tolerate further treatment) occurred on step 3 treatment and a biopsy was not performed at step 2 screening (due to presence of a
healthy Volunteers: false
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
Patients with EGFR activating mutation receive afatinib orally (PO) once daily (QD) on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT or MRI during screening and on study, as well as during follow-up as clinically necessary. Patients may also undergo ECHO or nuclear study throughout the trial as clinically necessary. Patients undergo biopsies and blood sample collection on study.
intervention Names
Drug: Afatinib
Drug: Afatinib Dimaleate
Procedure: Biopsy Procedure
Procedure: Biospecimen Collection
Procedure: Computed Tomography
Other: Cytology Specimen Collection Procedure
Procedure: Echocardiography Test
Other: Laboratory Biomarker Analysis
Procedure: Magnetic Resonance Imaging
Procedure: Radionuclide Imaging
label
Subprotocol A (EGFR activating mutation)
type
EXPERIMENTAL
description
Patients with HER2 activating mutation receive afatinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
intervention Names
Drug: Afatinib
Drug: Afatinib Dimaleate
Other: Cytology Specimen Collection Procedure
Other: Laboratory Biomarker Analysis
label
Subprotocol B (HER2 activating mutation)
type
EXPERIMENTAL
description
Patients with MET amplification receive crizotinib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo radiologic evaluation and collection of blood samples throughout the study. Patients may undergo biopsy at screening, on study, and/or at end of treatment.
intervention Names
Procedure: Biopsy Procedure
Procedure: Biospecimen Collection
Drug: Crizotinib
Other: Cytology Specimen Collection Procedure
Other: Laboratory Biomarker Analysis
Procedure: Radiologic Examination
label
Subprotocol C1 (MET amplification)
type
EXPERIMENTAL
description
Patients with MET exon 14 deletion or other mutations that disrupt exon 14 receive crizotinib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo tumor biopsy on study and undergo radiologic evaluation and blood sample collection throughout the study.
intervention Names
Procedure: Biopsy Procedure
Procedure: Biospecimen Collection
Drug: Crizotinib
Other: Cytology Specimen Collection Procedure
Other: Laboratory Biomarker Analysis
Procedure: Radiologic Examination
label
Subprotocol C2 (MET exon 14 deletion/mutation)
type
EXPERIMENTAL
description
Patients with EGFR T790M or rare activating mutation receive osimertinib (AZD9291) PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo radiologic evaluation throughout the trial, ECHO or multigated acquisition scan (MUGA) during screening, and biopsy and collection of blood samples on trial and at end of treatment.
intervention Names
Procedure: Biopsy Procedure
Procedure: Biospecimen Collection
Other: Cytology Specimen Collection Procedure
Procedure: Echocardiography Test
Other: Laboratory Biomarker Analysis
Procedure: Multigated Acquisition Scan
Drug: Osimertinib
Procedure: Radiologic Examination
label
Subprotocol E (EGFR T790M or rare activating mutation)
type
EXPERIMENTAL
description
Patients with ALK translocation receive crizotinib PO twice daily (BID) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
intervention Names
Drug: Crizotinib
Other: Cytology Specimen Collection Procedure
Other: Laboratory Biomarker Analysis
label
Subprotocol F (ALK translocation)
type
EXPERIMENTAL
description
Patients with ROS1 translocation or inversion receive crizotinib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
intervention Names
Drug: Crizotinib
Other: Cytology Specimen Collection Procedure
Other: Laboratory Biomarker Analysis
label
Subprotocol G (ROS1 translocation or inversion)
type
EXPERIMENTAL
description
Patients with BRAF V600E/R/K/D mutation receive dabrafenib PO BID and trametinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
intervention Names
Other: Cytology Specimen Collection Procedure
Drug: Dabrafenib
Drug: Dabrafenib Mesylate
Other: Laboratory Biomarker Analysis
Drug: Trametinib
label
Subprotocol H (BRAF V600E/R/K/D mutation)
type
EXPERIMENTAL
description
Patients with PIK3CA mutation without RAS mutation or PTEN loss receive taselisib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
intervention Names
Other: Cytology Specimen Collection Procedure
Other: Laboratory Biomarker Analysis
Drug: Taselisib
label
Subprotocol I (PIK3CA mutation)
type
EXPERIMENTAL
description
Patients receive pertuzumab IV over 30-60 minutes and trastuzumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Patients also undergo radiologic evaluation throughout the trial, ECHO at screening and end of treatment, and biopsy and collection of blood samples on trial and at end of treatment.
intervention Names
Procedure: Biopsy Procedure
Procedure: Biospecimen Collection
Procedure: Echocardiography Test
Other: Laboratory Biomarker Analysis
Biological: Pertuzumab
Procedure: Radiologic Examination
Biological: Trastuzumab
label
Subprotocol J (HER2 amplification >= 7 copy numbers)
type
EXPERIMENTAL
description
Patients with FGFR amplification receive erdafitinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT and MRI throughout study. Patients may also undergo blood sample collection and tumor biopsy throughout the trial.
intervention Names
Procedure: Biopsy Procedure
Procedure: Biospecimen Collection
Procedure: Computed Tomography
Other: Cytology Specimen Collection Procedure
Drug: Erdafitinib
Other: Laboratory Biomarker Analysis
Procedure: Magnetic Resonance Imaging
label
Subprotocol K1 (FGFR amplification)
type
EXPERIMENTAL
description
Patients with FGFR mutation or fusion receive erdafitinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection, CT or MRI, and tumor biopsy throughout the study.
intervention Names
Procedure: Biopsy Procedure
Procedure: Biospecimen Collection
Procedure: Computed Tomography
Other: Cytology Specimen Collection Procedure
Drug: Erdafitinib
Other: Laboratory Biomarker Analysis
Procedure: Magnetic Resonance Imaging
label
Subprotocol K2 (FGFR mutation or fusion)
type
EXPERIMENTAL

interventions

arm Group Labels
Subprotocol Z1I (BRCA1 or BRCA2 gene mutation)
description
Given PO
name
Adavosertib
other Names
AZD 1775
AZD-1775
AZD1775
MK 1775
MK-1775
MK1775
type
DRUG
arm Group Labels
Subprotocol A (EGFR activating mutation)
Subprotocol B (HER2 activating mutation)
description
Given PO
name
Afatinib
other Names
BIBW 2992
BIBW-2992
BIBW2992
type
DRUG
arm Group Labels
Subprotocol A (EGFR activating mutation)
Subprotocol B (HER2 activating mutation)
description
Given PO
name
Afatinib Dimaleate
other Names
(2E)-N-(4-((3-Chloro-4-fluorophenyl)amino)-7-(((3S)-tetrahydrofuran-3-yl)oxy)quinazolin- 6-yl)-4-(dimethylamino)but-2-enamide bis(hydrogen (2Z)-but-2-enedioate)
BIBW 2992MA2
BIBW2992 MA2
Gilotrif
type
DRUG
arm Group Labels
Subprotocol Z1A (NRAS mutation in codon 12, 13, or 61)
description
Given PO
name
Binimetinib
other Names
ARRY 162
ARRY 438162
ARRY-162
ARRY-438162
ARRY162
ARRY438162
MEK 162
MEK-162
MEK162
Mektovi
type
DRUG
arm Group Labels
Subprotocol A (EGFR activating mutation)
Subprotocol C1 (MET amplification)
Subprotocol C2 (MET exon 14 deletion/mutation)
Subprotocol E (EGFR T790M or rare activating mutation)
Subprotocol J (HER2 amplification >= 7 copy numbers)
Subprotocol K1 (FGFR amplification)
Subprotocol K2 (FGFR mutation or fusion)
Subprotocol T (SMO or PTCH1 mutation)
Subprotocol V (cKIT exon 9, 11, 13, or 14 mutation)
Subprotocol Z1E (NTRK1, NTRK2 or NTRK3 gene fusion)
Subprotocol Z1F (PIK3CA mutation)
description
Undergo tumor biopsy
name
Biopsy Procedure
other Names
Biopsy
BIOPSY_TYPE
Bx
type
PROCEDURE
arm Group Labels
Subprotocol A (EGFR activating mutation)
Subprotocol C1 (MET amplification)
Subprotocol C2 (MET exon 14 deletion/mutation)
Subprotocol E (EGFR T790M or rare activating mutation)
Subprotocol J (HER2 amplification >= 7 copy numbers)
Subprotocol K1 (FGFR amplification)
Subprotocol K2 (FGFR mutation or fusion)
Subprotocol T (SMO or PTCH1 mutation)
Subprotocol V (cKIT exon 9, 11, 13, or 14 mutation)
Subprotocol Z1E (NTRK1, NTRK2 or NTRK3 gene fusion)
description
Undergo collection of blood samples
name
Biospecimen Collection
other Names
Biological Sample Collection
Biospecimen Collected
Sample Collection
Specimen Collection
type
PROCEDURE
arm Group Labels
Subprotocol Y (Akt mutation)
description
Given PO
name
Capivasertib
other Names
AZD 5363
AZD-5363
AZD5363
Truqap
type
DRUG
arm Group Labels
Subprotocol A (EGFR activating mutation)
Subprotocol K1 (FGFR amplification)
Subprotocol K2 (FGFR mutation or fusion)
Subprotocol T (SMO or PTCH1 mutation)
Subprotocol V (cKIT exon 9, 11, 13, or 14 mutation)
Subprotocol Z1E (NTRK1, NTRK2 or NTRK3 gene fusion)
Subprotocol Z1F (PIK3CA mutation)
description
Undergo computed tomography (CT)
name
Computed Tomography
other Names
CAT
CAT Scan
Computed Axial Tomography
Computerized Axial Tomography
Computerized axial tomography (procedure)
Computerized Tomography
Computerized Tomography (CT) scan
CT
CT Scan
Diagnostic CAT Scan
Diagnostic CAT Scan Service Type
tomography
type
PROCEDURE
arm Group Labels
Subprotocol Z1F (PIK3CA mutation)
Subprotocol Z1G (PTEN loss)
Subprotocol Z1H (PTEN mutation)
description
Given IV
name
Copanlisib
other Names
BAY 80 6946
BAY 80-6946
BAY 806946
BAY-80-6946
BAY806946
PI3K Inhibitor BAY 80-6946
type
DRUG
arm Group Labels
Subprotocol Z1F (PIK3CA mutation)
Subprotocol Z1G (PTEN loss)
Subprotocol Z1H (PTEN mutation)
description
Given IV
name
Copanlisib Hydrochloride
other Names
5-Pyrimidinecarboxamide, 2-Amino-N-(2,3-dihydro-7-methoxy-8-(3-(4-morpholinyl)propoxy)imidazo(1,2-C)quinazolin-5-yl)-, Hydrochloride (1:2)
Aliqopa
BAY 80-6946 Dihydrochloride
BAY-80-6946 Dihydrochloride
Copanlisib Dihydrochloride
type
DRUG
arm Group Labels
Subprotocol C1 (MET amplification)
Subprotocol C2 (MET exon 14 deletion/mutation)
Subprotocol F (ALK translocation)
Subprotocol G (ROS1 translocation or inversion)
description
Given PO
name
Crizotinib
other Names
Alkixen
Crizocent
MET Tyrosine Kinase Inhibitor PF-02341066
PF 02341066
PF-02341066
PF-2341066
PF02341066
Xalkori
type
DRUG
arm Group Labels
Subprotocol A (EGFR activating mutation)
Subprotocol B (HER2 activating mutation)
Subprotocol C1 (MET amplification)
Subprotocol C2 (MET exon 14 deletion/mutation)
Subprotocol E (EGFR T790M or rare activating mutation)
Subprotocol F (ALK translocation)
Subprotocol G (ROS1 translocation or inversion)
Subprotocol H (BRAF V600E/R/K/D mutation)
Subprotocol I (PIK3CA mutation)
Subprotocol K1 (FGFR amplification)
Subprotocol K2 (FGFR mutation or fusion)
Subprotocol L (mTOR mutation)
description
Optional correlative studies
name
Cytology Specimen Collection Procedure
other Names
Cytologic Sampling
type
OTHER

Study design

allocation

NON_RANDOMIZED

intervention Model

PARALLEL

masking Info

masking: NONE

primary Purpose

SCREENING

Enrollment

count: 6452
type: ESTIMATED

Registered outcome plans (not posted results)

primary Outcomes

description
ORR is defined as the percentage of patients whose tumors have a complete or partial response to treatment among analyzable patients. Objective response is defined consistent with Response Evaluation Criteria in Solid Tumors version 1.1, the Cheson (2014) criteria for lymphoma patients, and the Response Assessment in Neuro-Oncology criteria for glioblastoma patients. 90% two-sided confidence interval is calculated for ORR. For the purposes of this study, patients should be re-evaluated for response: * For treatments given in 21 day (3 week) cycles: every 3 cycles (9 weeks) for the first 33 cycles, and every 4 cycles thereafter (12 weeks) * For treatments given in 28 day (4 week) cycles: every 2 cycles (8 weeks) for the first 26 cycles, and every three cycles thereafter (12 weeks) * For treatments given in 42 day (6 week) cycles: every 2 cycles (12 weeks)
measure
Objective response rate (ORR)
time Frame
Up to 3 years

secondary Outcomes

description
Will be evaluated specifically for each drug (or step). OS will be estimated using the Kaplan-Meier method.
measure
Overall survival (OS)
time Frame
From start of treatment on that step until death, or censored at the date of last contact, assessed up to 3 years
description
Progression free survival is defined as time from treatment start date to date of progression or death from any cause, whichever occurs first. Disease progression was evaluated using the Response Evaluation Criteria in Solid Tumors version 1.1, the Cheson (2014) criteria for lymphoma patients, and the Response Assessment in Neuro-Oncology criteria for glioblastoma patients. Please refer to the protocol for detailed definitions of disease progression. 6 month PFS rate was estimated using the Kaplan-Meier method, which can provide a point estimate for any specific time point.
measure
6-month progression free survival (PFS) rate
time Frame
From start of treatment on that step until determination of disease progression or death from any cause, censored at the date of last disease assessment for patients who have not progressed, assessed at 6 months
description
PFS was defined as time from treatment start date to date of disease progression or death from any causes, whichever occurred first. Median PFS was estimated using the Kaplan-Meier method. Disease progression was evaluated using the Response Evaluation Criteria in Solid Tumors version 1.1, the Cheson (2014) criteria for lymphoma patients, and the Response Assessment in Neuro-Oncology criteria for glioblastoma patients. Please refer to the protocol for detailed definitions of disease progression.
measure
Progression free survival
time Frame
From start of treatment on that step until determination of disease progression or death from any cause, censored at the date of last disease assessment for patients who have not progressed, assessed up to 3 years

Full study description

brief Summary: This phase II MATCH screening and multi-sub-trial studies how well treatment that is directed by genetic testing works in patients with solid tumors, lymphomas, or multiple myelomas that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) and does not respond to treatment (refractory). Patients must 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.
detailed Description: PRIMARY OBJECTIVE: 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 38 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. Additionally, patients may undergo a computed tomography (CT) scan, magnetic resonance imaging, and/or radionuclide imaging throughout the trial. After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 1 year.

Source references

references

citation
Tsao AS, Song Z, Ho AL, Mehnert JM, Ivy P, Gray RJ, Wang V, McShane LM, Rubinstein LV, Patton DR, Williams PM, Hamilton SR, Takebe N, Ajumally R, Silhavy J, Rahmanian S, Das B, Chen L, Karlovich C, Lococo JS, Tricoli JV, Conley BA, Arteaga CL, Harris LN, O'Dwyer PJ, Chen AP, Flaherty KT. Phase II Study of Vismodegib in Patients With SMO- or PTCH1-Mutated Tumors: Results From the National Cancer Institute Molecular Analysis for Therapy Choice Eastern Cooperative Oncology Group-American College of Radiology Imaging Network Trial (EAY131) Subprotocol T. JCO Precis Oncol. 2025 Oct;9:e2500119. doi: 10.1200/PO-25-00119. Epub 2025 Oct 9.
pmid
41066729
type
DERIVED
citation
Janku F, Jegede OA, Puhalla SL, Konstantinopoulos PA, Meric-Bernstam F, Zwiebel JA, Gray RJ, Wang XV, McShane LM, Rubinstein LV, Patton DR, Williams PM, Hamilton SR, Takebe N, Ghani S, Tricoli JV, Conley BA, Arteaga CL, Harris LN, O'Dwyer PJ, Chen AP, Flaherty KT. PIK3CB Inhibitor GSK2636771 in Cancers With PTEN Mutation/Deletion or Loss of PTEN Protein Expression: Results From the NCI-MATCH ECOG-ACRIN Trial (EAY131) Subprotocols N and P. JCO Precis Oncol. 2025 Aug;9:e2500265. doi: 10.1200/PO-25-00265. Epub 2025 Aug 27.
pmid
40865033
type
DERIVED
citation
Gouda MA, Wei Z, Rodon J, Davies MA, Janku F, Gray RJ, Wang V, McShane LM, Rubinstein LV, Patton DR, Williams PM, Hamilton SR, Liu R, Bota DA, Swiecicki PL, Buchschacher GL, Tricoli JV, Conley BA, Arteaga CL, Harris LN, O'Dwyer PJ, Chen AP, Flaherty KT. Phase II Study of Copanlisib in Patients With PTEN Loss: Results From NCI-MATCH ECOG-ACRIN Trial (EAY131) Subprotocols Z1G and Z1H. JCO Precis Oncol. 2025 Feb;9:e2400451. doi: 10.1200/PO-24-00451. Epub 2025 Feb 6.
pmid
39913886
type
DERIVED
citation
Zauderer MG, Jegede O, Jackman DM, Zwiebel JA, Gray RJ, Wang V, McShane LM, Rubinstein LV, Patton DR, Williams PM, Hamilton SR, Takebe N, Huang R, Carrillo JA, Brenner AJ, Tricoli JV, Conley BA, Arteaga CL, Harris LN, O'Dwyer PJ, Chen AP, Flaherty KT. Phase II Study of Defactinib (VS6063) in Patients With Tumors With NF2 Loss: Results From the NCI-MATCH ECOG-ACRIN Trial (EAY131) Subprotocol U. JCO Precis Oncol. 2024 Dec;8:e2400327. doi: 10.1200/PO.24.00327. Epub 2024 Dec 18.
pmid
39693587
type
DERIVED
citation
Gien LT, Song Z, Poklepovic A, Collisson EA, Zwiebel JA, Gray RJ, Wang V, McShane LM, Rubinstein LV, Patton DR, Williams PM, Hamilton SR, Tricoli JV, Conley BA, Arteaga CL, Harris LN, O'Dwyer PJ, Chen AP, Flaherty KT. Phase II Study of Sunitinib in Tumors With c-KIT Mutations: Results From the NCI MATCH ECOG-ACRIN Trial (EAY131) Subprotocol V. JCO Precis Oncol. 2024 Dec;8:e2400514. doi: 10.1200/PO-24-00514. Epub 2024 Dec 12.
pmid
39666929
type
DERIVED
citation
Chen MF, Song Z, Yu HA, Sequist LV, Lovly CM, Mitchell EP, Moscow JA, Gray RJ, Wang V, McShane LM, Rubinstein LV, Patton DR, Williams PM, Hamilton SR, Umemura Y, Tricoli JV, Conley BA, Arteaga CL, Harris LN, O'Dwyer PJ, Chen AP, Flaherty KT. Phase II Study of Osimertinib in Patients With Epidermal Growth Factor Receptor Mutations: Results From the NCI-MATCH ECOG-ACRIN (EAY131) Trial Subprotocol E. JCO Precis Oncol. 2024 Apr;8:e2300454. doi: 10.1200/PO.23.00454.
pmid
38591867
type
DERIVED
citation
Subbiah V, Burris HA 3rd, Kurzrock R. Revolutionizing cancer drug development: Harnessing the potential of basket trials. Cancer. 2024 Jan;130(2):186-200. doi: 10.1002/cncr.35085. Epub 2023 Nov 7.
pmid
37934000
type
DERIVED
citation
O'Dwyer PJ, Gray RJ, Flaherty KT, Chen AP, Li S, Wang V, McShane LM, Patton DR, Tricoli JV, Williams PM, Iafrate AJ, Sklar J, Mitchell EP, Takebe N, Sims DJ, Coffey B, Fu T, Routbort M, Rubinstein LV, Little RF, Arteaga CL, Marinucci D, Hamilton SR, Conley BA, Harris LN, Doroshow JH. The NCI-MATCH trial: lessons for precision oncology. Nat Med. 2023 Jun;29(6):1349-1357. doi: 10.1038/s41591-023-02379-4. Epub 2023 Jun 15.
pmid
37322121
type
DERIVED
citation
Wisinski KB, Flamand Y, Wilson MA, Luke JJ, Tawbi HA, Hong F, Mitchell EP, Zwiebel JA, Chen H, Gray RJ, Li S, McShane LM, Rubinstein LV, Patton D, Williams PM, Hamilton SR, Behrens RJ, Pennington KP, Conley BA, Arteaga CL, Harris LN, O'Dwyer PJ, Chen AP, Flaherty KT. Trametinib in Patients With NF1-, GNAQ-, or GNA11-Mutant Tumors: Results From the NCI-MATCH ECOG-ACRIN Trial (EAY131) Subprotocols S1 and S2. JCO Precis Oncol. 2023 Apr;7:e2200421. doi: 10.1200/PO.22.00421.
pmid
37053535
type
DERIVED
citation
Schrottmaier WC, Kral-Pointner JB, Salzmann M, Mussbacher M, Schmuckenschlager A, Pirabe A, Brunnthaler L, Kuttke M, Maier B, Heber S, Datler H, Ekici Y, Niederreiter B, Heber U, Blomgren B, Gorki AD, Soderberg-Naucler C, Payrastre B, Gratacap MP, Knapp S, Schabbauer G, Assinger A. Platelet p110beta mediates platelet-leukocyte interaction and curtails bacterial dissemination in pneumococcal pneumonia. Cell Rep. 2022 Nov 8;41(6):111614. doi: 10.1016/j.celrep.2022.111614.
pmid
36351402
type
DERIVED
citation
Krop IE, Jegede OA, Grilley-Olson JE, Lauring JD, Mitchell EP, Zwiebel JA, Gray RJ, Wang V, McShane LM, Rubinstein LV, Patton D, Williams PM, Hamilton SR, Kono SA, Ford JM, Garcia AA, Sui XD, Siegel RD, Slomovitz BM, Conley BA, Arteaga CL, Harris LN, O'Dwyer PJ, Chen AP, Flaherty KT. Phase II Study of Taselisib in PIK3CA-Mutated Solid Tumors Other Than Breast and Squamous Lung Cancer: Results From the NCI-MATCH ECOG-ACRIN Trial (EAY131) Subprotocol I. JCO Precis Oncol. 2022 Feb;6:e2100424. doi: 10.1200/PO.21.00424.
pmid
35138919
type
DERIVED
citation
Damodaran S, Zhao F, Deming DA, Mitchell EP, Wright JJ, Gray RJ, Wang V, McShane LM, Rubinstein LV, Patton DR, Williams PM, Hamilton SR, Suga JM, Conley BA, Arteaga CL, Harris LN, O'Dwyer PJ, Chen AP, Flaherty KT. Phase II Study of Copanlisib in Patients With Tumors With PIK3CA Mutations: Results From the NCI-MATCH ECOG-ACRIN Trial (EAY131) Subprotocol Z1F. J Clin Oncol. 2022 May 10;40(14):1552-1561. doi: 10.1200/JCO.21.01648. Epub 2022 Feb 8.
pmid
35133871
type
DERIVED