Targeted Therapy Directed By Genetic Testing In Treating Patients With Advanced Refractory Solid Tumors, Lymphomas, Or Multiple Myeloma (The MATCH Screening Trial)

Study Overview

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

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.

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.

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

DRUG: Adavosertib
DRUG: Afatinib
DRUG: Afatinib Dimaleate
DRUG: Binimetinib
PROCEDURE: Biopsy
PROCEDURE: Biospecimen Collection
DRUG: Capivasertib
PROCEDURE: Computed Tomography
DRUG: Copanlisib
DRUG: Copanlisib Hydrochloride
DRUG: Crizotinib
OTHER: Cytology Specimen Collection Procedure
DRUG: Dabrafenib
DRUG: Dabrafenib Mesylate
DRUG: Dasatinib
DRUG: Defactinib
DRUG: Defactinib Hydrochloride
PROCEDURE: Echocardiography
DRUG: Erdafitinib
DRUG: Fexagratinib
DRUG: Ipatasertib
OTHER: Laboratory Biomarker Analysis
DRUG: Larotrectinib
DRUG: Larotrectinib Sulfate
PROCEDURE: Magnetic Resonance Imaging
PROCEDURE: Multigated Acquisition Scan
BIOLOGICAL: Nivolumab
DRUG: Osimertinib
DRUG: Palbociclib
BIOLOGICAL: Pertuzumab
DRUG: PI3K-beta Inhibitor GSK2636771
PROCEDURE: Radiologic Examination
PROCEDURE: Radionuclide Imaging
BIOLOGICAL: Relatlimab
DRUG: Sapanisertib
DRUG: Sunitinib Malate
DRUG: Taselisib
DRUG: Trametinib
BIOLOGICAL: Trastuzumab
BIOLOGICAL: Trastuzumab Emtansine
DRUG: Ulixertinib
DRUG: Vismodegib

NCI-2015-00054
NCI-2015-00054 (REGISTRY Identifier) (REGISTRY: CTRP (Clinical Trial Reporting Program))
EAY131 (OTHER Identifier) (OTHER: ECOG-ACRIN Cancer Research Group)
EAY131 (OTHER Identifier) (OTHER: CTEP)
U10CA180820 (U.S. NIH Grant/Contract)
U24CA196172 (U.S. NIH Grant/Contract)

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2015-06-03	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2025-03-26
First Submitted that Met QC Criteria 2015-06-03	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2025-03-27
First Posted (ACTUAL) 2015-06-08	Results First Posted N/A	Last Verified 2024-11

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Other

Allocation:
Non Randomized

Interventional Model:
Parallel

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
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 scr	DRUG: Afatinib Given PO DRUG: Afatinib Dimaleate Given PO PROCEDURE: Biopsy Undergo tumor biopsy PROCEDURE: Biospecimen Collection Undergo collection of blood samples PROCEDURE: Computed Tomography Undergo computed tomography (CT) OTHER: Cytology Specimen Collection Procedure Optional correlative studies PROCEDURE: Echocardiography Undergo echocardiography (ECHO) OTHER: Laboratory Biomarker Analysis Undergo molecular analysis PROCEDURE: Magnetic Resonance Imaging Undergo magnetic resonance imaging (MRI) PROCEDURE: Radionuclide Imaging Undergo nuclear study
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 Given PO DRUG: Afatinib Dimaleate Given PO OTHER: Cytology Specimen Collection Procedure Optional correlative studies OTHER: Laboratory Biomarker Analysis Undergo molecular 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	PROCEDURE: Biopsy Undergo tumor biopsy PROCEDURE: Biospecimen Collection Undergo collection of blood samples DRUG: Crizotinib Given PO OTHER: Cytology Specimen Collection Procedure Optional correlative studies OTHER: Laboratory Biomarker Analysis Undergo molecular analysis PROCEDURE: Radiologic Examination Undergo radiologic evaluation
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 under	PROCEDURE: Biopsy Undergo tumor biopsy PROCEDURE: Biospecimen Collection Undergo collection of blood samples DRUG: Crizotinib Given PO OTHER: Cytology Specimen Collection Procedure Optional correlative studies OTHER: Laboratory Biomarker Analysis Undergo molecular analysis PROCEDURE: Radiologic Examination Undergo radiologic evaluation
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 th	PROCEDURE: Biopsy Undergo tumor biopsy PROCEDURE: Biospecimen Collection Undergo collection of blood samples OTHER: Cytology Specimen Collection Procedure Optional correlative studies PROCEDURE: Echocardiography Undergo echocardiography (ECHO) OTHER: Laboratory Biomarker Analysis Undergo molecular analysis PROCEDURE: Multigated Acquisition Scan Undergo MUGA DRUG: Osimertinib Given PO PROCEDURE: Radiologic Examination Undergo radiologic evaluation
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 Given PO OTHER: Cytology Specimen Collection Procedure Optional correlative studies OTHER: Laboratory Biomarker Analysis Undergo molecular 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 Given PO
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.	DRUG: Dabrafenib Given PO DRUG: Dabrafenib Mesylate Given PO DRUG: Trametinib Given PO
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.	DRUG: Taselisib Given PO
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	PROCEDURE: Biopsy Undergo tumor biopsy PROCEDURE: Biospecimen Collection Undergo collection of blood samples PROCEDURE: Echocardiography Undergo echocardiography (ECHO) BIOLOGICAL: Pertuzumab Given IV PROCEDURE: Radiologic Examination Undergo radiologic evaluation BIOLOGICAL: Trastuzumab Given IV
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	PROCEDURE: Computed Tomography Undergo computed tomography (CT) DRUG: Erdafitinib Given PO PROCEDURE: Magnetic Resonance Imaging Undergo magnetic resonance imaging (MRI)
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 t	PROCEDURE: Computed Tomography Undergo computed tomography (CT) DRUG: Erdafitinib Given PO PROCEDURE: Magnetic Resonance Imaging Undergo magnetic resonance imaging (MRI)
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.	DRUG: Sapanisertib Given PO
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.	DRUG: Sapanisertib Given PO
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.	DRUG: PI3K-beta Inhibitor GSK2636771 Given PO
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.	DRUG: PI3K-beta Inhibitor GSK2636771 Given PO
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.	BIOLOGICAL: Trastuzumab Given IV BIOLOGICAL: Trastuzumab Emtansine Given IV
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.	DRUG: Trametinib Given PO
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.	DRUG: Trametinib Given PO
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.	DRUG: Trametinib Given PO
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 sc	PROCEDURE: Computed Tomography Undergo computed tomography (CT) PROCEDURE: Echocardiography Undergo echocardiography (ECHO) PROCEDURE: Magnetic Resonance Imaging Undergo magnetic resonance imaging (MRI) PROCEDURE: Radionuclide Imaging Undergo nuclear study DRUG: Vismodegib Given PO
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.	DRUG: Defactinib Given PO DRUG: Defactinib Hydrochloride Given PO
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	PROCEDURE: Computed Tomography Undergo computed tomography (CT) PROCEDURE: Echocardiography Undergo echocardiography (ECHO) PROCEDURE: Magnetic Resonance Imaging Undergo magnetic resonance imaging (MRI) PROCEDURE: Radionuclide Imaging Undergo nuclear study DRUG: Sunitinib Malate Given PO
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.	DRUG: Fexagratinib Given PO
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.	DRUG: Dasatinib Given PO
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 Given PO
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 Given PO
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.	DRUG: Palbociclib Given PO
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.	DRUG: Palbociclib Given PO
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 to	BIOLOGICAL: Nivolumab Given IV
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 durin	DRUG: Larotrectinib Given PO DRUG: Larotrectinib Sulfate Given PO
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	DRUG: Copanlisib Given IV DRUG: Copanlisib Hydrochloride Given IV
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 Given IV DRUG: Copanlisib Hydrochloride Given IV
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 Given IV DRUG: Copanlisib Hydrochloride Given IV
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 Given PO
EXPERIMENTAL: Subprotocol Z1K (AKT mutation) Patients receive ipatasertib PO QD. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.	DRUG: Ipatasertib Given PO
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.	DRUG: Ulixertinib Give PO
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.	BIOLOGICAL: Nivolumab Given IV BIOLOGICAL: Relatlimab Given IV

Primary Outcome Measures	Measure Description	Time Frame
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)	Up to 3 years

Secondary Outcome Measures	Measure Description	Time Frame
Overall survival (OS)	Will be evaluated specifically for each drug (or step). OS will be estimated using the Kaplan-Meier method.	From start of treatment on that step until death, or censored at the date of last contact, assessed up to 3 years
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.	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
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.	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

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

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 sexual orientation or 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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

PRINCIPAL_INVESTIGATOR: Keith T Flaherty, ECOG-ACRIN Cancer Research Group

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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. Erratum In: JCO Precis Oncol. 2022 Mar;6:e2200116. doi: 10.1200/PO.22.00116.
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.
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.
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.
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.

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