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Active, not recruitingNCT02465060Updated Aug 28, 2026

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

A Phase 2 interventional study of Adavosertib and Afatinib in Advanced Lymphoma, Advanced Malignant Solid Neoplasm and Bladder Carcinoma, sponsored by National Cancer Institute (NCI). Active, not recruiting at 1,410 sites in 3 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-08-28.

Sponsored by National Cancer Institute (NCI) · Phase 2, Interventional, and Screening

Phase
Phase 2
Study type
Interventional
Enrollment
6,452
Allocation
Non-randomized
Ages
18 Years and older
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • Advanced Lymphoma
  • Advanced Malignant Solid Neoplasm
  • Bladder Carcinoma
  • Breast Carcinoma
  • Cervical Carcinoma
  • Colon Carcinoma
  • Colorectal Carcinoma
  • Endometrial Carcinoma
  • Esophageal Carcinoma
  • Exocrine Pancreas Carcinoma
  • Gastric Carcinoma
  • Glioma
  • Head and Neck Carcinoma
  • Hematopoietic and Lymphoid Cell Neoplasm
  • Kidney Carcinoma
  • Liver Carcinoma
  • Lung Carcinoma
  • Lymphoma
  • Malignant Uterine Corpus Neoplasm
  • Malignant Uterine Neoplasm
  • Melanoma
  • Multiple Myeloma
  • Ovarian Carcinoma
  • Prostate Carcinoma
  • Rectal Carcinoma
  • Recurrent Bladder Carcinoma
  • Recurrent Breast Carcinoma
  • Recurrent Cervical Carcinoma
  • Recurrent Colon Carcinoma
  • Recurrent Colorectal Carcinoma
  • Recurrent Esophageal Carcinoma
  • Recurrent Gastric Carcinoma
  • Recurrent Glioma
  • Recurrent Head and Neck Carcinoma
  • Recurrent Liver Carcinoma
  • Recurrent Lung Carcinoma
  • Recurrent Lymphoma
  • Recurrent Malignant Solid Neoplasm
  • Recurrent Malignant Uterine Corpus Neoplasm
  • Recurrent Melanoma
  • Recurrent Multiple Myeloma
  • Recurrent Ovarian Carcinoma
  • Recurrent Pancreatic Carcinoma
  • Recurrent Prostate Carcinoma
  • Recurrent Rectal Carcinoma
  • Recurrent Skin Carcinoma
  • Recurrent Thyroid Gland Carcinoma
  • Refractory Lymphoma
  • Refractory Malignant Solid Neoplasm
  • Refractory Multiple Myeloma
  • Skin Carcinoma
  • Thyroid Gland Carcinoma
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

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
04

Study design

Phase
Phase 2
Primary purpose
Screening
Allocation
Non-randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
6,452 participants (estimated)

Study arms

  • Experimental
    Subprotocol A (EGFR activating mutation)

    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.

    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

  • Experimental
    Subprotocol B (HER2 activating mutation)

    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.

    Drug: Afatinib · Drug: Afatinib Dimaleate · Other: Cytology Specimen Collection Procedure · Other: Laboratory Biomarker Analysis

  • Experimental
    Subprotocol C1 (MET amplification)

    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.

    Procedure: Biopsy Procedure · Procedure: Biospecimen Collection · Drug: Crizotinib · Other: Cytology Specimen Collection Procedure · Other: Laboratory Biomarker Analysis · Procedure: Radiologic Examination

  • Experimental
    Subprotocol C2 (MET exon 14 deletion/mutation)

    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.

    Procedure: Biopsy Procedure · Procedure: Biospecimen Collection · Drug: Crizotinib · Other: Cytology Specimen Collection Procedure · Other: Laboratory Biomarker Analysis · Procedure: Radiologic Examination

  • Experimental
    Subprotocol E (EGFR T790M or rare activating mutation)

    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.

    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

  • Experimental
    Subprotocol F (ALK translocation)

    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.

    Drug: Crizotinib · Other: Cytology Specimen Collection Procedure · Other: Laboratory Biomarker Analysis

  • Experimental
    Subprotocol G (ROS1 translocation or inversion)

    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.

    Drug: Crizotinib · Other: Cytology Specimen Collection Procedure · Other: Laboratory Biomarker Analysis

  • Experimental
    Subprotocol H (BRAF V600E/R/K/D mutation)

    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.

    Other: Cytology Specimen Collection Procedure · Drug: Dabrafenib · Drug: Dabrafenib Mesylate · Other: Laboratory Biomarker Analysis · Drug: Trametinib

  • Experimental
    Subprotocol I (PIK3CA mutation)

    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.

    Other: Cytology Specimen Collection Procedure · Other: Laboratory Biomarker Analysis · Drug: Taselisib

  • Experimental
    Subprotocol J (HER2 amplification >= 7 copy numbers)

    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.

    Procedure: Biopsy Procedure · Procedure: Biospecimen Collection · Procedure: Echocardiography Test · Other: Laboratory Biomarker Analysis · Biological: Pertuzumab · Procedure: Radiologic Examination · Biological: Trastuzumab

  • Experimental
    Subprotocol K1 (FGFR amplification)

    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.

    Procedure: Biopsy Procedure · Procedure: Biospecimen Collection · Procedure: Computed Tomography · Other: Cytology Specimen Collection Procedure · Drug: Erdafitinib · Other: Laboratory Biomarker Analysis · Procedure: Magnetic Resonance Imaging

  • Experimental
    Subprotocol K2 (FGFR mutation or fusion)

    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.

    Procedure: Biopsy Procedure · Procedure: Biospecimen Collection · Procedure: Computed Tomography · Other: Cytology Specimen Collection Procedure · Drug: Erdafitinib · Other: Laboratory Biomarker Analysis · Procedure: Magnetic Resonance Imaging

  • Experimental
    Subprotocol L (mTOR mutation)

    Patients with mTOR mutation receive sapanisertib PO daily on days 1-28. Cycles repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.

    Other: Cytology Specimen Collection Procedure · Other: Laboratory Biomarker Analysis · Drug: Sapanisertib

  • Experimental
    Subprotocol M (TSC1 or TSC2 mutation)

    Patients with TSC1 or TSC2 mutation receive sapanisertib PO daily on days 1-28. Cycles repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.

    Other: Cytology Specimen Collection Procedure · Other: Laboratory Biomarker Analysis · Drug: Sapanisertib

  • Experimental
    Subprotocol N (PTEN mutation or deletion and PTEN expression)

    Patients with PTEN mutation or deletion and PTEN expression receive PI3K-beta inhibitor GSK2636771 PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

    Other: Cytology Specimen Collection Procedure · Other: Laboratory Biomarker Analysis · Drug: PI3K-beta Inhibitor GSK2636771

  • Experimental
    Subprotocol P (PTEN loss)

    Patients with PTEN loss receive PI3K-beta inhibitor GSK2636771 PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

    Other: Cytology Specimen Collection Procedure · Other: Laboratory Biomarker Analysis · Drug: PI3K-beta Inhibitor GSK2636771

  • Experimental
    Subprotocol Q (HER2 amplification)

    Patients with HER2 amplification receive trastuzumab emtansine intravenously (IV) over 30-90 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

    Other: Cytology Specimen Collection Procedure · Other: Laboratory Biomarker Analysis · Biological: Trastuzumab · Biological: Trastuzumab Emtansine

  • Experimental
    Subprotocol R (BRAF fusion or BRAF non-V600 mutation)

    Patients with BRAF fusion or BRAF non-V600 mutation receive trametinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

    Other: Cytology Specimen Collection Procedure · Other: Laboratory Biomarker Analysis · Drug: Trametinib

  • Experimental
    Subprotocol S1 (NF1 mutation)

    Patients with NF1 mutation receive trametinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

    Other: Cytology Specimen Collection Procedure · Other: Laboratory Biomarker Analysis · Drug: Trametinib

  • Experimental
    Subprotocol S2 (GNAQ or GNA11 mutation)

    Patients with GNAQ or GNA11 mutation receive trametinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

    Other: Cytology Specimen Collection Procedure · Other: Laboratory Biomarker Analysis · Drug: Trametinib

  • Experimental
    Subprotocol T (SMO or PTCH1 mutation)

    Patients with SMO or PTCH1 mutation receive vismodegib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO or nuclear study during screening, tumor biopsy on study and CT scan, MRI and blood sample collection throughout the study.

    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 · Drug: Vismodegib

  • Experimental
    Subprotocol U (NF2 inactivating mutation)

    Patients with NF2 inactivating mutation receive defactinib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

    Other: Cytology Specimen Collection Procedure · Drug: Defactinib · Drug: Defactinib Hydrochloride · Other: Laboratory Biomarker Analysis

  • Experimental
    Subprotocol V (cKIT exon 9, 11, 13, or 14 mutation)

    Patients with cKIT exon 9, 11, 13, or 14 mutation receive sunitinib PO QD on days 1-28 of each cycle. Cycles repeat every 42 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 also undergo ECHO or nuclear study throughout the trial as clinically necessary. Patients undergo biopsies and blood sample collection on study.

    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 · Drug: Sunitinib Malate

  • Experimental
    Subprotocol W (FGFR pathway aberrations)

    Patients with FGFR1-3 mutation or translocation receive FGFR Inhibitor AZD4547 PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

    Other: Cytology Specimen Collection Procedure · Drug: Fexagratinib · Other: Laboratory Biomarker Analysis

  • Experimental
    Subprotocol X (DDR2 S768R, I638F, or L239R mutation)

    Patients with DDR2 S768R, I638F, or L239R mutation receive dasatinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

    Other: Cytology Specimen Collection Procedure · Drug: Dasatinib · Other: Laboratory Biomarker Analysis

  • Experimental
    Subprotocol Y (Akt mutation)

    Patients with Akt mutation receive capivasertib PO BID on days 1-4, 8-11, 15-18, and 22-25. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

    Drug: Capivasertib · Other: Cytology Specimen Collection Procedure · Other: Laboratory Biomarker Analysis

  • Experimental
    Subprotocol Z1A (NRAS mutation in codon 12, 13, or 61)

    Patients with NRAS mutation in codon 12, 13, or 61 receive binimetinib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

    Drug: Binimetinib · Other: Cytology Specimen Collection Procedure · Other: Laboratory Biomarker Analysis

  • Experimental
    Subprotocol Z1B (CCND1, 2, or 3 amplification with Rb by IHC)

    Patients with CCND1, 2, or 3 amplification that have tumor Rb expression by IHC receive palbociclib PO QD for 21 days. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

    Other: Cytology Specimen Collection Procedure · Other: Laboratory Biomarker Analysis · Drug: Palbociclib

  • Experimental
    Subprotocol Z1C (CDK4 or CDK6 amplification and Rb protein)

    Patients with CDK4 or CDK6 amplification and tumor Rb protein receive palbociclib PO QD on days 1-21. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

    Other: Cytology Specimen Collection Procedure · Other: Laboratory Biomarker Analysis · Drug: Palbociclib

  • Experimental
    Subprotocol Z1D (Loss of MLH1 or MSH2 by IHC)

    Patients with mismatch repair deficiency (loss of MLH1 or MSH2 by IHC) receive nivolumab IV over 30 minutes on days 1 and 15 for 4 cycles and then on day 1 every 28 days. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

    Other: Cytology Specimen Collection Procedure · Other: Laboratory Biomarker Analysis · Biological: Nivolumab

  • Experimental
    Subprotocol Z1E (NTRK1, NTRK2 or NTRK3 gene fusion)

    Patients with NTRK1, NTRK2, or NTRK3 gene fusion receive larotrectinib (LOXO-101) PO BID 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 also undergo biopsies and blood sample collection on study.

    Procedure: Biopsy Procedure · Procedure: Biospecimen Collection · Procedure: Computed Tomography · Other: Cytology Specimen Collection Procedure · Other: Laboratory Biomarker Analysis · Drug: Larotrectinib · Drug: Larotrectinib Sulfate · Procedure: Magnetic Resonance Imaging

  • Experimental
    Subprotocol Z1F (PIK3CA mutation)

    Patients receive copanlisib IV over 1 hour on days 1, 8, and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo tumor biopsies at screening and end of treatment as well as CT or MRI at baseline and repeated every 2 cycles for the first 26 cycles then every 3 cycles thereafter until progressive disease or start of another MATCH treatment step.

    Procedure: Biopsy Procedure · Procedure: Computed Tomography · Drug: Copanlisib · Drug: Copanlisib Hydrochloride · Other: Cytology Specimen Collection Procedure · Procedure: Magnetic Resonance Imaging

  • Experimental
    Subprotocol Z1G (PTEN loss)

    Patients with PTEN loss receive copanlisib IV over 1 hour on days 1, 8, and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

    Drug: Copanlisib · Drug: Copanlisib Hydrochloride · Other: Cytology Specimen Collection Procedure · Other: Laboratory Biomarker Analysis

  • Experimental
    Subprotocol Z1H (PTEN mutation)

    Patients with PTEN mutation receive copanlisib IV over 1 hour on days 1, 8, and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

    Drug: Copanlisib · Drug: Copanlisib Hydrochloride · Other: Cytology Specimen Collection Procedure · Other: Laboratory Biomarker Analysis

  • Experimental
    Subprotocol Z1I (BRCA1 or BRCA2 gene mutation)

    Patients with BRCA1 or BRCA2 gene mutation receive adavosertib PO QD for 5 days for 2 weeks. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

    Drug: Adavosertib · Other: Cytology Specimen Collection Procedure · Other: Laboratory Biomarker Analysis

  • Experimental
    Subprotocol Z1K (AKT mutation)

    Patients receive ipatasertib PO QD. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

    Other: Cytology Specimen Collection Procedure · Drug: Ipatasertib · Other: Laboratory Biomarker Analysis

  • Experimental
    Subprotocol Z1L (BRAF fusion, aberration or non-V600 mutation)

    Patients with a BRAF non-V600 mutation or BRAF fusion, or another BRAF aberration receive ulixertinib (BVD-523FB) PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

    Other: Cytology Specimen Collection Procedure · Other: Laboratory Biomarker Analysis · Drug: Ulixertinib

  • Experimental
    Subprotocol Z1M (LAG-3 expression >= 1%)

    Patients receive nivolumab IV over 30 minutes and relatlimab IV over 30 minutes on day 1.Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

    Other: Cytology Specimen Collection Procedure · Other: Laboratory Biomarker Analysis · Biological: Nivolumab · Biological: Relatlimab

Interventions

  • DrugAdavosertib

    Given PO

    Also known as: AZD 1775, AZD-1775, AZD1775, MK 1775, MK-1775, MK1775

  • DrugAfatinib

    Given PO

    Also known as: BIBW 2992, BIBW-2992, BIBW2992

  • DrugAfatinib Dimaleate

    Given PO

    Also known as: (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

  • DrugBinimetinib

    Given PO

    Also known as: ARRY 162, ARRY 438162, ARRY-162, ARRY-438162, ARRY162, ARRY438162, MEK 162, MEK-162, MEK162, Mektovi

  • ProcedureBiopsy Procedure

    Undergo tumor biopsy

    Also known as: Biopsy, BIOPSY_TYPE, Bx

  • ProcedureBiospecimen Collection

    Undergo collection of blood samples

    Also known as: Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection

  • DrugCapivasertib

    Given PO

    Also known as: AZD 5363, AZD-5363, AZD5363, Truqap

  • ProcedureComputed Tomography

    Undergo computed tomography (CT)

    Also known as: 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

  • DrugCopanlisib

    Given IV

    Also known as: BAY 80 6946, BAY 80-6946, BAY 806946, BAY-80-6946, BAY806946, PI3K Inhibitor BAY 80-6946

  • DrugCopanlisib Hydrochloride

    Given IV

    Also known as: 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

  • DrugCrizotinib

    Given PO

    Also known as: Alkixen, Crizocent, MET Tyrosine Kinase Inhibitor PF-02341066, PF 02341066, PF-02341066, PF-2341066, PF02341066, Xalkori

  • OtherCytology Specimen Collection Procedure

    Optional correlative studies

    Also known as: Cytologic Sampling

  • DrugDabrafenib

    Given PO

    Also known as: BRAF Inhibitor GSK2118436, GSK 2118436, GSK 2118436A, GSK-2118436, GSK-2118436A, GSK2118436, GSK2118436A

  • DrugDabrafenib Mesylate

    Given PO

    Also known as: Dabrafenib Methanesulfonate, GSK2118436 Methane Sulfonate Salt, GSK2118436B, Tafinlar

  • DrugDasatinib

    Given PO

    Also known as: BMS 354825, BMS-354825, BMS354825, Dasatinib Hydrate, Dasatinib Monohydrate, Sprycel

  • DrugDefactinib

    Given PO

    Also known as: PF-04554878, VS-6063

  • DrugDefactinib Hydrochloride

    Given PO

  • ProcedureEchocardiography Test

    Undergo echocardiography (ECHO)

    Also known as: EC, Echocardiography

  • DrugErdafitinib

    Given PO

    Also known as: Balversa, JNJ 42756493, JNJ-42756493, JNJ42756493

  • DrugFexagratinib

    Given PO

    Also known as: ABSK-091, ABSK091, AZD4547, FGFR Inhibitor AZD4547, KB-74810

  • DrugIpatasertib

    Given PO

    Also known as: GDC 0068, GDC-0068, GDC0068, RG 7440, RG-7440, RG7440

  • OtherLaboratory Biomarker Analysis

    Undergo molecular analysis

  • DrugLarotrectinib

    Given PO

    Also known as: ARRY 470, LOXO 101, LOXO-101, LOXO101

  • DrugLarotrectinib Sulfate

    Given PO

    Also known as: ARRY 470 Sulfate, LOXO 101 Sulfate, LOXO-101 Sulfate, Vitrakvi

  • ProcedureMagnetic Resonance Imaging

    Undergo magnetic resonance imaging (MRI)

    Also known as: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI

  • ProcedureMultigated Acquisition Scan

    Undergo MUGA

    Also known as: Blood Pool Scan, Equilibrium Radionuclide Angiography, Gated Blood Pool Imaging, Gated Heart Pool Scan, MUGA, MUGA Scan, Multi-Gated Acquisition Scan, Radionuclide Ventriculogram Scan, Radionuclide Ventriculography, RNV Scan, RNVG, SYMA Scanning, Synchronized Multigated Acquisition Scanning

  • BiologicalNivolumab

    Given IV

    Also known as: ABP 206, BCD-263, BMS 936558, BMS-936558, BMS936558, CMAB819, MDX 1106, MDX-1106, MDX1106, NIVO, Nivolumab Biosimilar ABP 206, Nivolumab Biosimilar BCD-263, Nivolumab Biosimilar CMAB819, ONO 4538, ONO-4538, ONO4538, Opdivo

  • DrugOsimertinib

    Given PO

    Also known as: AZD 9291, AZD-9291, AZD9291, Mereletinib

  • DrugPalbociclib

    Given PO

    Also known as: 6-Acetyl-8-cyclopentyl-5-methyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)-8h-pyrido(2,3-d)pyrimidin-7-one, Ibrance, PD 0332991, PD 332991, PD 991, PD-0332991, PD0332991

  • BiologicalPertuzumab

    Given IV

    Also known as: 2C4, 2C4 Antibody, BCD-178, EG1206A, HLX11, HS627, MoAb 2C4, Monoclonal Antibody 2C4, Omnitarg, Perjeta, Pertuzumab Biosimilar BCD-178, Pertuzumab Biosimilar EG1206A, Pertuzumab Biosimilar HLX11, Pertuzumab Biosimilar HS627, Pertuzumab Biosimilar TQB2440, Pertuzumab-dpzb, Poherdy, Rhumab 2C4, rhuMAb2C4, RO4368451, TQB 2440, TQB-2440, TQB2440

  • DrugPI3K-beta Inhibitor GSK2636771

    Given PO

    Also known as: GSK-2636771, GSK2636771

  • ProcedureRadiologic Examination

    Undergo radiologic evaluation

    Also known as: Radiologic Evaluation, Radiologic Exam

  • ProcedureRadionuclide Imaging

    Undergo nuclear study

    Also known as: Gamma Scan, NM, Nuclear Medicine, nuclear medicine scan, radioimaging, Radionuclide Scanning, Scan, Scintigraphy

  • BiologicalRelatlimab

    Given IV

    Also known as: BMS 986016, BMS-986016, BMS986016, Immunoglobulin G4, Anti-(human Lymphocyte Activation Gene-3 Protein) (Human Heavy Chain), Disulfide with Human Light Chain, Dimer

  • DrugSapanisertib

    Given PO

    Also known as: INK-128, INK128, MLN-0128, MLN0128, TAK-228

  • DrugSunitinib Malate

    Given PO

    Also known as: SU 011248, SU 11248, SU-011248, SU-11248, SU011248, SU11248, sunitinib, Sutent

  • DrugTaselisib

    Given PO

    Also known as: GDC-0032, RO5537381

  • DrugTrametinib

    Given PO

    Also known as: GSK 1120212, GSK 212, GSK-1120212, GSK-212, GSK1120212, GSK212, JTP 74057, JTP-74057, JTP74057, MEK Inhibitor GSK1120212

  • BiologicalTrastuzumab

    Given IV

    Also known as: ABP 980, ALT02, Biceltis, CANMab, CT-P06, CT-P6, Herceptin, Herceptin Biosimilar PF-05280014, Herceptin Trastuzumab Biosimilar PF-05280014, Hercessi, Herclon, Hertraz, Herwenda, Herzuma, HLX 02, HLX-02, HLX02, Kanjinti, Ogivri, Ontruzant, PF 05280014, PF-05280014, PF05280014, QL 1701, QL-1701, QL1701, rhuMAb HER2, RO0452317, SB3, Trastuzumab Biosimilar ABP 980, Trastuzumab Biosimilar ALT02, Trastuzumab Biosimilar CT-P6, trastuzumab biosimilar EG12014, Trastuzumab Biosimilar HLX02, Trastuzumab Biosimilar PF-05280014, Trastuzumab Biosimilar QL1701, Trastuzumab Biosimilar SB3, Trastuzumab Biosimilar SIBP-01, Trastuzumab-anns, Trastuzumab-dkst, Trastuzumab-dttb, Trastuzumab-herw, Trastuzumab-pkrb, Trastuzumab-qyyp, Trastuzumab-strf, Trastuzumab-tuzn, Trastuzumab-zerc, Trazimera, Tuznue, Zercepac

  • BiologicalTrastuzumab Emtansine

    Given IV

    Also known as: Ado Trastuzumab Emtansine, ADO-Trastuzumab Emtansine, Kadcyla, PRO 132365, PRO-132365, PRO132365, RO5304020, T-DM1, TDM1, Trastuzumab-DM1, Trastuzumab-MCC-DM1, Trastuzumab-MCC-DM1 Antibody-Drug Conjugate, Trastuzumab-MCC-DM1 Immunoconjugate

  • DrugUlixertinib

    Give PO

    Also known as: BVD-523, VRT752271

  • DrugVismodegib

    Given PO

    Also known as: Erivedge, GDC 0449, GDC-0449, GDC0449, Hedgehog Antagonist GDC-0449

05

What researchers measure

Primary outcomes

  1. Objective response rate (ORR)

    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)

    Time frame: Up to 3 years

Secondary outcomes

  1. Overall survival (OS)

    Will be evaluated specifically for each drug (or step). OS will be estimated using the Kaplan-Meier method.

    Time frame: From start of treatment on that step until death, or censored at the date of last contact, assessed up to 3 years

  2. 6-month progression free survival (PFS) rate

    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.

    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

  3. Progression free survival

    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.

    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

06

Study locations

1,410 sites
  • University of Alabama at Birmingham Cancer Center
    Birmingham, Alabama 35233, United States
  • Thomas Hospital
    Fairhope, Alabama 36532, United States
  • Mobile Infirmary Medical Center
    Mobile, Alabama 36607, United States
  • University of South Alabama Mitchell Cancer Institute
    Mobile, Alabama 36688, United States
  • Anchorage Associates in Radiation Medicine
    Anchorage, Alaska 98508, United States
  • Anchorage Radiation Therapy Center
    Anchorage, Alaska 99504, United States
  • Alaska Breast Care and Surgery LLC
    Anchorage, Alaska 99508, United States
  • Alaska Oncology and Hematology LLC
    Anchorage, Alaska 99508, United States
  • Alaska Regional Hospital
    Anchorage, Alaska 99508, United States
  • Alaska Women's Cancer Care
    Anchorage, Alaska 99508, United States
  • Anchorage Oncology Centre
    Anchorage, Alaska 99508, United States
  • Katmai Oncology Group
    Anchorage, Alaska 99508, United States
  • Providence Alaska Medical Center
    Anchorage, Alaska 99508, United States
  • Fairbanks Memorial Hospital
    Fairbanks, Alaska 99701, United States
  • CTCA at Western Regional Medical Center
    Goodyear, Arizona 85338, United States
  • Kingman Regional Medical Center
    Kingman, Arizona 86401, United States
  • Cancer Center at Saint Joseph's
    Phoenix, Arizona 85004, United States
  • Saint Joseph's Hospital and Medical Center
    Phoenix, Arizona 85013, United States
  • Mayo Clinic Hospital in Arizona
    Phoenix, Arizona 85054, United States
  • Mayo Clinic in Arizona
    Scottsdale, Arizona 85259, United States
  • Mercy Hospital Fort Smith
    Fort Smith, Arkansas 72903, United States
  • CHI Saint Vincent Cancer Center Hot Springs
    Hot Springs, Arkansas 71913, United States
  • NEA Baptist Memorial Hospital and Fowler Family Cancer Center - Jonesboro
    Jonesboro, Arkansas 72401, United States
  • University of Arkansas for Medical Sciences
    Little Rock, Arkansas 72205, United States
  • Kaiser Permanente-Anaheim
    Anaheim, California 92806, United States
  • Kaiser Permanente-Deer Valley Medical Center
    Antioch, California 94531, United States
  • Mission Hope Medical Oncology - Arroyo Grande
    Arroyo Grande, California 93420, United States
  • PCR Oncology
    Arroyo Grande, California 93420, United States
  • Sutter Auburn Faith Hospital
    Auburn, California 95602, United States
  • Sutter Cancer Centers Radiation Oncology Services-Auburn
    Auburn, California 95603, United States
  • AIS Cancer Center at San Joaquin Community Hospital
    Bakersfield, California 93301, United States
  • Kaiser Permanente-Baldwin Park
    Baldwin Park, California 91706, United States
  • Kaiser Permanente-Bellflower
    Bellflower, California 90706, United States
  • Alta Bates Summit Medical Center-Herrick Campus
    Berkeley, California 94704, United States
  • Providence Saint Joseph Medical Center/Disney Family Cancer Center
    Burbank, California 91505, United States
  • Mills-Peninsula Medical Center
    Burlingame, California 94010, United States
  • Sutter Cancer Centers Radiation Oncology Services-Cameron Park
    Cameron Park, California 95682, United States
  • Eden Hospital Medical Center
    Castro Valley, California 94546, United States
  • Community Cancer Institute
    Clovis, California 93611, United States
  • University Oncology Associates
    Clovis, California 93611, United States
  • John Muir Medical Center-Concord
    Concord, California 94520, United States
  • City of Hope Corona
    Corona, California 92882, United States
  • UC Irvine Health Cancer Center-Newport
    Costa Mesa, California 92627, United States
  • Sutter Davis Hospital
    Davis, California 95616, United States
  • City of Hope Comprehensive Cancer Center
    Duarte, California 91010, United States
  • Epic Care-Dublin
    Dublin, California 94568, United States
  • Kaiser Permanente Dublin
    Dublin, California 94568, United States
  • Bay Area Breast Surgeons Inc
    Emeryville, California 94608, United States
  • Epic Care Partners in Cancer Care
    Emeryville, California 94608, United States
  • Kaiser Permanente-Fontana
    Fontana, California 92335, United States
  • Kaiser Permanente-Fremont
    Fremont, California 94538, United States
  • Palo Alto Medical Foundation-Fremont
    Fremont, California 94538, United States
  • Fresno Cancer Center
    Fresno, California 93720, United States
  • Kaiser Permanente-Fresno
    Fresno, California 93720, United States
  • Saint Jude Medical Center
    Fullerton, California 92835, United States
  • Marin Cancer Care Inc
    Greenbrae, California 94904, United States
  • Marin General Hospital
    Greenbrae, California 94904, United States
  • Kaiser Permanente South Bay
    Harbor City, California 90710, United States
  • Kaiser Permanente-Irvine
    Irvine, California 92618, United States
  • UC San Diego Moores Cancer Center
    La Jolla, California 92093, United States
  • Loma Linda University Medical Center
    Loma Linda, California 92354, United States
  • Kaiser Permanente Los Angeles Medical Center
    Los Angeles, California 90027, United States
  • Los Angeles General Medical Center
    Los Angeles, California 90033, United States
  • USC / Norris Comprehensive Cancer Center
    Los Angeles, California 90033, United States
  • Kaiser Permanente West Los Angeles
    Los Angeles, California 90034, United States
  • Cedars-Sinai Medical Center
    Los Angeles, California 90048, United States
  • Contra Costa Regional Medical Center
    Martinez, California 94553-3156, United States
  • Fremont - Rideout Cancer Center
    Marysville, California 95901, United States
  • Memorial Medical Center
    Modesto, California 95355, United States
  • Kaiser Permanente-Modesto
    Modesto, California 95356, United States
  • Community Hospital of Monterey Peninsula
    Monterey, California 93940, United States
  • Pacific Cancer Care-Monterey
    Monterey, California 93940, United States
  • Palo Alto Medical Foundation-Camino Division
    Mountain View, California 94040, United States
  • Palo Alto Medical Foundation-Gynecologic Oncology
    Mountain View, California 94040, United States
  • USC Norris Oncology/Hematology-Newport Beach
    Newport Beach, California 92663, United States
  • Sutter Cancer Research Consortium
    Novato, California 94945, United States
  • Alta Bates Summit Medical Center - Summit Campus
    Oakland, California 94609, United States
  • Bay Area Tumor Institute
    Oakland, California 94609, United States
  • Kaiser Permanente Oakland-Broadway
    Oakland, California 94611, United States
  • Kaiser Permanente-Oakland
    Oakland, California 94611, United States
  • Kaiser Permanente-Ontario
    Ontario, California 91761, United States
  • Saint Joseph Hospital - Orange
    Orange, California 92868, United States
  • UC Irvine Health/Chao Family Comprehensive Cancer Center
    Orange, California 92868, United States
  • Desert Regional Medical Center
    Palm Springs, California 92262, United States
  • Palo Alto Medical Foundation Health Care
    Palo Alto, California 94301, United States
  • Stanford Cancer Institute Palo Alto
    Palo Alto, California 94304, United States
  • VA Palo Alto Health Care System
    Palo Alto, California 94304, United States
  • Kaiser Permanente - Panorama City
    Panorama City, California 91402, United States
  • Keck Medical Center of USC Pasadena
    Pasadena, California 91105, United States
  • Kaiser Permanente-Rancho Cordova Cancer Center
    Rancho Cordova, California 95670, United States
  • Eisenhower Medical Center
    Rancho Mirage, California 92270, United States
  • Kaiser Permanente- Marshall Medical Offices
    Redwood City, California 94063, United States
  • Kaiser Permanente-Redwood City
    Redwood City, California 94063, United States
  • Kaiser Permanente-Richmond
    Richmond, California 94801, United States
  • Kaiser Permanente-Riverside
    Riverside, California 92505, United States
  • Rohnert Park Cancer Center
    Rohnert Park, California 94928, United States
  • Kaiser Permanente-Roseville
    Roseville, California 95661, United States
  • Sutter Cancer Centers Radiation Oncology Services-Roseville
    Roseville, California 95661, United States
  • Sutter Roseville Medical Center
    Roseville, California 95661, United States
  • The Permanente Medical Group-Roseville Radiation Oncology
    Roseville, California 95678, United States

Showing the first 100 of 1,410 sites across 3 countries.

07

References and documents

Publications

  • 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. PubMed 41066729 ↗
  • 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. PubMed 40865033 ↗
  • 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. PubMed 39913886 ↗
  • 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. PubMed 39693587 ↗
  • 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. PubMed 39666929 ↗
  • 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. PubMed 38591867 ↗
  • 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. PubMed 37934000 ↗
  • 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. PubMed 37322121 ↗
  • 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. PubMed 37053535 ↗
  • 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. PubMed 36351402 ↗
  • 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. PubMed 35138919 ↗
  • 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. PubMed 35133871 ↗
  • Flaherty KT, Gray RJ, Chen AP, Li S, McShane LM, Patton D, Hamilton SR, Williams PM, Iafrate AJ, Sklar J, Mitchell EP, Harris LN, Takebe N, Sims DJ, Coffey B, Fu T, Routbort M, Zwiebel JA, Rubinstein LV, Little RF, Arteaga CL, Comis R, Abrams JS, O'Dwyer PJ, Conley BA; NCI-MATCH team. Molecular Landscape and Actionable Alterations in a Genomically Guided Cancer Clinical Trial: National Cancer Institute Molecular Analysis for Therapy Choice (NCI-MATCH). J Clin Oncol. 2020 Nov 20;38(33):3883-3894. doi: 10.1200/JCO.19.03010. Epub 2020 Oct 13. PubMed 33048619 ↗
  • Chae YK, Hong F, Vaklavas C, Cheng HH, Hammerman P, Mitchell EP, Zwiebel JA, Ivy SP, Gray RJ, Li S, McShane LM, Rubinstein LV, Patton D, Williams PM, Hamilton SR, Mansfield A, Conley BA, Arteaga CL, Harris LN, O'Dwyer PJ, Chen AP, Flaherty KT. Phase II Study of AZD4547 in Patients With Tumors Harboring Aberrations in the FGFR Pathway: Results From the NCI-MATCH Trial (EAY131) Subprotocol W. J Clin Oncol. 2020 Jul 20;38(21):2407-2417. doi: 10.1200/JCO.19.02630. Epub 2020 May 28. PubMed 32463741 ↗
  • Moore KN, Mannel RS. Is the NCI MATCH trial a match for gynecologic oncology? Gynecol Oncol. 2016 Jan;140(1):161-6. doi: 10.1016/j.ygyno.2015.11.003. Epub 2015 Nov 14. PubMed 26586415 ↗

Related links

Study documents

  • Protocol and statistical analysis plan · Oct 9, 2020

Documents are hosted by the registry — open the source record to download them.

08

Registry details

Key details

Study ID
NCT02465060
Lead sponsor
National Cancer Institute (NCI)
Responsible party
Sponsor
First posted
Jun 8, 2015
Start date
Aug 17, 2015
Primary completion
Dec 31, 2026 (estimated)
Completion
Dec 31, 2026 (estimated)
Last update
Aug 28, 2026

Study contacts

Keith T Flaherty
principal investigator · ECOG-ACRIN Cancer Research Group

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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