A Phase 2 interventional study of Alpelisib and Binimetinib in Advanced Malignant Solid Neoplasm, Anatomic Stage III Breast Cancer AJCC v8 and Anatomic Stage IV Breast Cancer AJCC v8, sponsored by National Cancer Institute (NCI). Recruiting at 484 sites in 2 countries. Per ClinicalTrials.gov, last updated 2026-11-02.
Sponsored by National Cancer Institute (NCI) · Phase 2, Interventional, and Screening
This ComboMATCH patient screening trial is the gateway to a coordinated set of clinical trials to study cancer treatment directed by genetic testing. Patients with solid tumors that have spread to nearby tissue or lymph nodes (locally advanced) or have spread to other places in the body (advanced) and have progressed on at least one line of standard systemic therapy or have no standard treatment that has been shown to prolong overall survival may be candidates for these trials. Genetic tests look at the unique genetic material (genes) of patients' tumor cells. Patients with some genetic changes or abnormalities (mutations) may benefit from treatment that targets that particular genetic mutation. ComboMATCH is designed to match patients to a treatment that may work to control their tumor and may help doctors plan better treatment for patients with locally advanced or advanced solid tumors.
PRIMARY OBJECTIVE:
I. To register, allocate, and assign patients to ComboMATCH treatment trials.
SECONDARY OBJECTIVES:
I. To evaluate the rate of positive outcomes in defined cohorts within treatment trials of treatment combinations including targeted therapies for molecularly defined populations, and also in the subset of treatment trials where the treatments are supported by in vivo models.
II. To perform quality control of the patients registered in the form of pathological confirmation of disease and sub-type to confirm diagnosis and treatment arm allocation.
SECONDARY CORRELATIVE OBJECTIVES:
I. Assess the concordance of the central molecular characterization of the pre-treatment biopsy samples with the genetic readouts from the Designated Laboratories (DLs) for patients enrolled on the ComboMATCH treatment trials.
II. To assess how the registration diagnostic tumor mutation profile and pre-treatment biopsy profile compare to the circulating tumor-derived deoxyribonucleic acid (ctDNA) mutation profile from plasma.
EXPLORATORY OBJECTIVE:
I. Assess association between ComboMATCH treatment trials outcomes (positive or negative) with the type of rationale for the selected drug combinations and the type of rationale for the gene variant/combination for selection (e.g., whether the trial was based on targeted therapies for molecularly defined populations, those that were supported by in vivo models, and those that were supported by empiric clinical data).
OUTLINE:
REGISTRATION: Patients undergo tumor mutational screening of previously-collected tumor samples for specific, pre-defined mutations, amplifications, or translocations of interest via tumor sequencing. Patients who are 18 years or older and have biopsiable disease undergo a new biopsy for research purposes prior to initiating treatment on the ComboMATCH treatment trial.
TREATMENT: Patients with mutations targeted to investigational combination therapies are assigned to 1 of 20 treatment subprotocols.
EAY191-N4: Patients with RAS pathway mutant ovarian or endometrial cancer are randomized to 1 of 2 arms.
ARM I: Patients receive selumetinib orally (PO) twice daily (BID) and olaparib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo a tumor biopsy and blood collection during screening and on study, as well as echocardiogram (ECHO) or multigated acquisition (MUGA), and computed tomography (CT) scans throughout the trial. Patients may undergo bone marrow aspiration or biopsy as clinically indicated.
ARM II: Patients receive selumetinib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients who experience progression may elect to cross over to Arm I provided they have not had dose limiting toxicities to monotherapy selumetinib. Patients also undergo a tumor biopsy and blood collection during screening and on study, as well as ECHO or MUGA, and CT scans throughout the trial. Patients may undergo bone marrow aspiration or biopsy as clinically indicated.
EAY191-N2: Patients with inactivating or inferred inactivating NF1 alterations, and hormone receptor positive, HER2-negative metastatic breast cancer. Patients who are fulvestrant naive are assigned to Cohort I, while patients who are fulvestrant resistant are assigned to Cohort II.
COHORT I: Patients are randomized to 1 of 2 arms.
ARM I:Patients receive fulvestrant intramuscularly (IM) on day 1 and day 15 of cycle 1 and day 1 of subsequent cycles and binimetinib PO BID on days 15 to 28 of cycle 1 and day 1 through 28 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo a CT, magnetic resonance imaging (MRI), or bone scan, ECHO or MUGA, and tumor biopsy, as well as possible blood sample collection during screening and on study.
ARM II: Patients receive fulvestrant IM on day 1 and day 15 of cycle 1 and day 1 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients who progress on fulvestrant alone may migrate to cohort II if they meet the migration eligibility criteria. Patients not willing to migrate to cohort II will have further therapy at the investigator's discretion. Patients undergo a CT, MRI, or bone scan and tumor biopsy, as well as ECHO or MUGA and possible blood sample collection during screening and on study.
COHORT II: Patients receive fulvestrant IM on day 1 of each cycle and binimetinib PO BID on days 15-28 of cycle 1 and day 1 through 28 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo a CT, MRI, or bone scan, ECHO or MUGA and tumor biopsy, as well as possible blood sample collection during screening and on study.
EAY191-E4: Patients with solid tumors who previously underwent taxane therapy.
Patients receive nilotinib hydrochloride monohydrate PO BID on days 1-28 and paclitaxel intravenously (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 undergo CT or MRI during screening or cycle 1 day 1, every 2 cycles for 1 year, every 3 cycles for patients on study for more than 1 year, and every 4 cycles for patients on study for more than 3 years and may also undergo CT or MRI during follow-up every 3 months for 2 years and then every 6 months for 1 year if clinically indicated. Patients also undergo collection of blood samples at baseline, cycle 2 day 1, and optionally at progression as well as tumor biopsy at baseline and optionally at progression.
EAY191-A3: Patients with KRAS/NRAS/BRAF mutated low-grade serous ovarian cancer (LGSOC) naive to MEK or CDK4/6 inhibitor therapy are randomized to either combination cohort 1 or monotherapy cohort 1. Patients with LGSOC who have received prior MEK inhibitor therapy are assigned to combination cohort 2. Patients with KRAS/NRAS/HRAS/non-V600E BRAF mutated pancreatic cancer are assigned to combination cohort 3. Patients with all other KRAS/NRAS/HRAS mutated tumor types (excluding LGSOC, non-small cell lung cancer, colorectal cancer, pancreatic, and melanoma) are assigned to combination cohort 4.
COMBINATION COHORTS 1, 2, 3, 4: Patients receive palbociclib PO and binimetinib PO throughout the trial. Patients may also undergo biopsy at screening and undergo MRI, CT, bone scan, and collection of blood samples during screening, on study, and/or during follow up.
MONOTHERAPY COHORT 1: Patients receive binimetinib PO throughout the trial. Patients may also undergo biopsy at screening and undergo MRI, CT, bone scan, and collection of blood samples during screening, on study, and/or during follow up.
EAY191-S3: Patients with an activating AKT mutation solid tumor.
Patients receive paclitaxel IV on days 1, 8, and 15 and ipatasertib PO on days 1-21 of each cycle. Treatment repeats every 28 days for up to 35 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo a CT or MRI and blood collection throughout the trial. Patients also undergo a tumor biopsy during screening and optionally during follow-up.
EAY191-A6: Patients with RAS/RAF/MEK/ERK mutant biliary tract cancers are randomized to 1 of 2 arms.
ARM 1: Patients receive leucovorin IV, oxaliplatin IV, and fluorouracil IV on study. Patients undergo echocardiogram (ECHO) and multigated acquisition scan (MUGA) during screening and on study, a CT with contrast, MRI, or a fludeoxyglucose F-18 positron emission tomography (FDG-PET) during screening, collection of blood during screening and on study, and a biopsy during screening. Patients may also undergo brain MRI or CT during screening and on study, bone scans on study, and biopsy on study if clinically indicated.
ARM 2: Patients receive binimetinib PO, leucovorin IV, oxaliplatin IV, and fluorouracil IV on study. Patients undergo ECHO and MUGA during screening and on study, a CT with contrast, MRI, or an FDG-PET during screening, collection of blood during screening and on study, and a biopsy during screening. Patients may also undergo brain MRI or CT during screening and on study, bone scans on study, and biopsy on study if clinically indicated.
EAY191-E5: Patients are assigned to 1 of 2 cohorts.
COHORT I: Patients who have never received a KRAS G12C inhibitor are randomized to arms A or B.
ARM A: Patients receive sotorasib PO once daily (QD) on days 1-28 and panitumumab intravenously IV on days 1 and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood samples, biopsy, and CT or MRI on study.
ARM B: Patients receive sotorasib PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with disease progression may cross-over to cohort II. Patients also undergo collection of blood samples, biopsy, and CT or MRI on study.
COHORT II: Patients who have received a KRAS G12C inhibitor are assigned to arm C.
ARM C: Patients receive combination therapy as in Arm A.
EAY191-A2: Patients are assigned to 1 of 3 cohorts.
COHORT 1: PARP-inhibitor naive patients are assigned to Arm A.
ARM A: Patients receive olaparib PO BID and alpelisib PO daily on days 1-28 of each cycle. Cycles repeat every 28 days for up to 5 years in the absence of disease progression, unacceptable toxicity, or bone marrow findings consistent with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). Patients also undergo MRI, CT, and/or PET scans throughout the trial and a biopsy prior to treatment start. Patients may also undergo bone scans on study as clinically indicated. Patients have the option to also undergo blood collection throughout the trial and a second biopsy at time of disease progression.
COHORT 2: PARP-inhibitor naive patients are randomized to 1 of 2 arms.
ARM B: Patients receive olaparib PO BID and alpelisib PO daily on days 1-28 of each cycle. Cycles repeat every 28 days for up to 5 years in the absence of disease progression, unacceptable toxicity, or bone marrow findings consistent with MDS or AML. Patients also undergo MRI, CT, and/or PET scans throughout the trial and a biopsy prior to treatment start. Patients may also undergo bone scans on study as clinically indicated. Patients have the option to also undergo blood collection throughout the trial and a second biopsy at time of disease progression.
ARM C: Patients receive olaparib PO BID on days 1-28 of each cycle. Cycles repeat every 28 days for up to 5 years in the absence of disease progression, unacceptable toxicity, or bone marrow findings consistent with MDS or AML. Patients experiencing disease progression have the option to migrate to Cohort 3, Arm D. Patients also undergo MRI, CT, and/or PET scans throughout the trial and a biopsy prior to treatment start. Patients may also undergo bone scans on study as clinically indicated. Patients have the option to also undergo blood collection throughout the trial and a second biopsy at time of disease progression.
COHORT 3: PARP-inhibitor resistant patients are assigned to Arm D.
ARM D: Patients receive olaparib PO BID and alpelisib PO daily on days 1-28 of each cycle. Cycles repeat every 28 days for up to 5 years in the absence of disease progression, unacceptable toxicity, or bone marrow findings consistent with MDS or AML. Patients also undergo MRI, CT, and/or PET scans throughout the trial and a biopsy prior to treatment start. Patients may also undergo bone scans on study as clinically indicated. Patients have the option to also undergo blood collection throughout the trial and a second biopsy at time of disease progression.
EAY191-N5: Patients are randomized to 1 of 2 arms.
ARM I: Patients receive neratinib maleate PO QD on days 1-14 of cycle 0 in the absence of disease progression or unacceptable toxicity. Patients then receive neratinib maleate PO QD on days 1-28 of each subsequent cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients who experience progression may crossover to Arm II. Patients undergo ECHO or MUGA during screening and on study, and CT or MRI and collection of blood samples throughout the trial. Patients may also undergo tumor biopsy during screening and on study.
ARM II: Patients receive neratinib maleate PO QD on days 1-14 of cycle 0 in the absence of disease progression or unacceptable toxicity. Patients then receive neratinib maleate PO QD on days 1-28 and palbociclib PO QD on days 1-21 of each subsequent cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO or MUGA during screening and on study, and CT or MRI and collection of blood samples throughout the trial. Patients may also undergo tumor biopsy during screening and on study.
4,040 studies on the registry are indexed under Neoplasm Metastasis; 886 are open to participants now.
This study's planned enrollment of 2,900 is above the median of 50 across 3,268 interventional studies indexed under Neoplasm Metastasis.
Browse Neoplasm Metastasis studies →National Cancer Institute (NCI) is the lead sponsor of 3,556 studies on the registry; 336 are open to participants now.
Of its 411 completed or terminated interventional studies of FDA-regulated products, 373 (91%) have results posted.
Counted across the registry records on this site, refreshed daily.
Inclusion Criteria:
Patients must have locally advanced or advanced documented solid tumors requiring therapy and meet one of the following criteria:
Patient must meet one of the following requirements:
Patients 18 years and older who do not have disease that is biopsiable at minimal risk to the patient must confirm availability of an archival tumor tissue specimen for submission for research if the patient enrolls to a ComboMATCH Treatment Trial. This tumor tissue must meet the following criteria:
Patients under 18 years old must confirm availability of an archival tumor tissue specimen for submission for research if patient enrolls to a ComboMATCH Treatment Trial. This tumor tissue must meet the following criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The amount of disease can be tracked with a defined measurement, so the study can see whether it shrinks or grows. It might be a tumour measured on a scan or, in some blood cancers such as myeloma, a marker measured in blood or urine.
The criteria or the study team say which measurement counts — having no tumour visible on a scan does not by itself rule you out.
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
A 0–100 scale of how well someone can carry out everyday activities. 100 is no complaints and no signs of illness; 70 is able to look after yourself but not to work or keep up normal activity; 50 is needing considerable help and frequent medical care.
Studies often ask for 60 or 70 and above. Your doctor gives the score.
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
The standard rules for measuring tumours on CT or MRI scans, to tell whether a cancer is shrinking, stable or growing during treatment.
“Measurable disease per RECIST 1.1” usually means at least one tumour 10 mm or more at its longest on a CT scan, or a lymph node 15 mm or more across its short axis.
Measurable disease
The amount of disease can be tracked with a defined measurement, so the study can see whether it shrinks or grows. It might be a tumour measured on a scan or, in some blood cancers such as myeloma, a marker measured in blood or urine.
The criteria or the study team say which measurement counts — having no tumour visible on a scan does not by itself rule you out.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECOG performance status
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Karnofsky performance status (KPS)
A 0–100 scale of how well someone can carry out everyday activities. 100 is no complaints and no signs of illness; 70 is able to look after yourself but not to work or keep up normal activity; 50 is needing considerable help and frequent medical care.
Studies often ask for 60 or 70 and above. Your doctor gives the score.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Histologically or cytologically confirmed
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Biopsy and archival tissue
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
RECIST
The standard rules for measuring tumours on CT or MRI scans, to tell whether a cancer is shrinking, stable or growing during treatment.
“Measurable disease per RECIST 1.1” usually means at least one tumour 10 mm or more at its longest on a CT scan, or a lymph node 15 mm or more across its short axis.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cohort 1, Arm A: Patients receive olaparib PO BID and alpelisib PO daily on days 1-28 of each cycle. Cycles repeat every 28 days for up to 5 years in the absence of disease progression, unacceptable toxicity, or bone marrow findings consistent with MDS or AML. Patients also undergo MRI, CT, and/or PET scans throughout the trial and a biopsy prior to treatment start. Patients may also undergo bone scans on study as clinically indicated. Patients have the option to also undergo blood collection throughout the trial and a second biopsy at time of disease progression.
Drug: Alpelisib · Procedure: Biopsy Procedure · Procedure: Biospecimen Collection · Procedure: Bone Scan · Procedure: Computed Tomography · Procedure: Magnetic Resonance Imaging · Drug: Olaparib · Procedure: Positron Emission Tomography
Cohort 2, Arm B: Patients receive olaparib PO BID and alpelisib PO daily on days 1-28 of each cycle. Cycles repeat every 28 days for up to 5 years in the absence of disease progression, unacceptable toxicity, or bone marrow findings consistent with MDS or AML. Patients also undergo MRI, CT, and/or PET scans throughout the trial and a biopsy prior to treatment start. Patients may also undergo bone scans on study as clinically indicated. Patients have the option to also undergo blood collection throughout the trial and a second biopsy at time of disease progression.
Drug: Alpelisib · Procedure: Biopsy Procedure · Procedure: Biospecimen Collection · Procedure: Bone Scan · Procedure: Computed Tomography · Procedure: Magnetic Resonance Imaging · Drug: Olaparib · Procedure: Positron Emission Tomography
Cohort 2, Arm C: Patients receive olaparib PO BID on days 1-28 of each cycle. Cycles repeat every 28 days for up to 5 years in the absence of disease progression, unacceptable toxicity, or bone marrow findings consistent with MDS or AML. Patients experiencing disease progression have the option to migrate to Cohort 3, Arm D. Patients also undergo MRI, CT, and/or PET scans throughout the trial and a biopsy prior to treatment start. Patients may also undergo bone scans on study as clinically indicated. Patients have the option to also undergo blood collection throughout the trial and a second biopsy at time of disease progression.
Procedure: Biopsy Procedure · Procedure: Biospecimen Collection · Procedure: Bone Scan · Procedure: Computed Tomography · Procedure: Magnetic Resonance Imaging · Drug: Olaparib · Procedure: Positron Emission Tomography
Cohort 3, Arm D: Patients receive olaparib PO BID and alpelisib PO daily on days 1-28 of each cycle. Cycles repeat every 28 days for up to 5 years in the absence of disease progression, unacceptable toxicity, or bone marrow findings consistent with MDS or AML. Patients also undergo MRI, CT, and/or PET scans throughout the trial and a biopsy prior to treatment start. Patients may also undergo bone scans on study as clinically indicated. Patients have the option to also undergo blood collection throughout the trial and a second biopsy at time of disease progression.
Drug: Alpelisib · Procedure: Biopsy Procedure · Procedure: Biospecimen Collection · Procedure: Bone Scan · Procedure: Computed Tomography · Drug: Olaparib · Procedure: Positron Emission Tomography
Patients receive palbociclib PO and binimetinib PO throughout the trial. Patients may also undergo biopsy at screening and undergo MRI, CT, bone scan, and collection of blood samples during screening, on study, and/or during follow up.
Procedure: Biopsy Procedure · Procedure: Biospecimen Collection · Procedure: Bone Scan · Procedure: Computed Tomography · Procedure: Magnetic Resonance Imaging · Drug: Palbociclib
Patients receive binimetinib PO throughout the trial. Patients may also undergo biopsy at screening and undergo MRI, CT, bone scan, and collection of blood samples during screening, on study, and/or during follow up.
Drug: Binimetinib · Procedure: Biopsy Procedure · Procedure: Biospecimen Collection · Procedure: Bone Scan · Procedure: Computed Tomography · Procedure: Magnetic Resonance Imaging
Patients receive leucovorin IV, oxaliplatin IV, and fluorouracil IV on study. Patients undergo ECHO and MUGA during screening and on study, a CT with contrast, MRI, or a FDG-PET during screening, collection of blood during screening and on study, and a biopsy during screening. Patients may also undergo brain MRI or CT during screening and on study, bone scans on study, and biopsy on study if clinically indicated.
Procedure: Biopsy Procedure · Procedure: Biospecimen Collection · Procedure: Bone Scan · Procedure: Computed Tomography · Procedure: Echocardiography Test · Drug: Fluorouracil · Drug: Leucovorin · Procedure: Magnetic Resonance Imaging · Procedure: Multigated Acquisition Scan · Drug: Oxaliplatin · Procedure: Positron Emission Tomography
Patients receive binimetinib PO, leucovorin IV, oxaliplatin IV, and fluorouracil IV on study. Patients undergo ECHO and MUGA during screening and on study, a CT with contrast, MRI, or an FDG-PET during screening, collection of blood during screening and on study, and a biopsy during screening. Patients may also undergo brain MRI or CT during screening and on study, bone scans on study, and biopsy on study if clinically indicated
Drug: Binimetinib · Procedure: Biospecimen Collection · Procedure: Bone Scan · Procedure: Computed Tomography · Procedure: Echocardiography Test · Drug: Fluorouracil · Drug: Leucovorin · Procedure: Magnetic Resonance Imaging · Procedure: Multigated Acquisition Scan · Drug: Oxaliplatin · Procedure: Positron Emission Tomography
Patients receive nilotinib hydrochloride monohydrate PO BID on days 1-28 and paclitaxel 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 undergo CT or MRI during screening or cycle 1 day 1, every 2 cycles for 1 year, every 3 cycles for patients on study for more than 1 year, and every 4 cycles for patients on study for more than 3 years and may also undergo CT or MRI during follow-up every 3 months for 2 years and then every 6 months for 1 year if clinically indicated. Patients also undergo collection of blood samples at baseline, cycle 2 day 1, and optionally at progression as well as tumor biopsy at baseline and optionally at progression.
Procedure: Biopsy Procedure · Procedure: Biospecimen Collection · Procedure: Computed Tomography · Procedure: Magnetic Resonance Imaging · Drug: Nilotinib Hydrochloride Monohydrate · Drug: Paclitaxel
Patients receive sotorasib PO QD on days 1-28 and panitumumab IV on days 1 and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood samples, biopsy, and CT or MRI on study.
Procedure: Biopsy Procedure · Procedure: Biospecimen Collection · Procedure: Computed Tomography · Procedure: Magnetic Resonance Imaging · Biological: Panitumumab · Drug: Sotorasib
Patients receive sotorasib PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with disease progression may cross-over to cohort II. Patients also undergo collection of blood samples, biopsy, and CT or MRI on study.
Procedure: Biopsy Procedure · Procedure: Biospecimen Collection · Procedure: Computed Tomography · Procedure: Magnetic Resonance Imaging · Drug: Sotorasib
Patients receive combination therapy as in EAY191-E5 Arm A.
Procedure: Biopsy Procedure · Procedure: Biospecimen Collection · Procedure: Computed Tomography · Procedure: Magnetic Resonance Imaging · Biological: Panitumumab · Drug: Sotorasib
Patients receive fulvestrant IM on day 1 and day 15 of cycle 1 and day 1 of subsequent cycles and binimetinib PO BID on days 15 to 28 of cycle 1 and day 1 through 28 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo a CT, MRI, or bone scan, ECHO or MUGA, and tumor biopsy, as well as possible blood sample collection during screening and on study.
Drug: Binimetinib · Procedure: Biopsy Procedure · Procedure: Biospecimen Collection · Procedure: Bone Scan · Procedure: Computed Tomography · Procedure: Echocardiography Test · Drug: Fulvestrant · Procedure: Magnetic Resonance Imaging · Procedure: Multigated Acquisition Scan
Patients receive fulvestrant IM on day 1 and day 15 of cycle 1 and day 1 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients who progress on fulvestrant alone may migrate to cohort II if they meet the migration eligibility criteria. Patients not willing to migrate to cohort II will have further therapy at the investigator's discretion. Patients undergo a CT, MRI, or bone scan and tumor biopsy, as well as ECHO or MUGA and possible blood sample collection during screening and on study.
Procedure: Biopsy Procedure · Procedure: Biospecimen Collection · Procedure: Bone Scan · Procedure: Computed Tomography · Procedure: Echocardiography Test · Drug: Fulvestrant · Procedure: Magnetic Resonance Imaging · Procedure: Multigated Acquisition Scan
Patients receive fulvestrant IM on day 1 of each cycle and binimetinib PO BID on days 15-28 of cycle 1 and day 1 through 28 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo a CT, MRI, or bone scan, ECHO or MUGA and tumor biopsy, as well as possible blood sample collection during screening and on study.
Drug: Binimetinib · Procedure: Biopsy Procedure · Procedure: Biospecimen Collection · Procedure: Bone Scan · Procedure: Computed Tomography · Procedure: Echocardiography Test · Drug: Fulvestrant · Procedure: Magnetic Resonance Imaging · Procedure: Multigated Acquisition Scan
Patients receive selumetinib PO BID and olaparib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo a tumor biopsy and blood collection during screening and on study, as well as ECHO or MUGA, and CT scans throughout the trial. Patients may undergo bone marrow aspiration or biopsy as clinically indicated.
Procedure: Biopsy Procedure · Procedure: Biospecimen Collection · Procedure: Bone Marrow Aspiration · Procedure: Bone Marrow Biopsy · Procedure: Computed Tomography · Procedure: Echocardiography Test · Procedure: Multigated Acquisition Scan · Procedure: Mutation Carrier Screening · Drug: Olaparib · Drug: Selumetinib Sulfate
Patients receive selumetinib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients who experience progression may elect to cross over to Arm I provided they have not had dose limiting toxicities to monotherapy selumetinib. Patients also undergo a tumor biopsy and blood collection during screening and on study, as well as ECHO or MUGA, and CT scans throughout the trial. Patients may undergo bone marrow aspiration or biopsy as clinically indicated.
Procedure: Biopsy Procedure · Procedure: Biospecimen Collection · Procedure: Bone Marrow Aspiration · Procedure: Bone Marrow Biopsy · Procedure: Computed Tomography · Procedure: Echocardiography Test · Procedure: Multigated Acquisition Scan · Procedure: Mutation Carrier Screening · Drug: Selumetinib Sulfate
Patients receive neratinib maleate PO QD on days 1-14 of cycle 0 in the absence of disease progression or unacceptable toxicity. Patients then receive neratinib maleate PO QD on days 1-28 of each subsequent cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients who experience progression may crossover to Arm II. Patients undergo ECHO or MUGA during screening and on study, and CT or MRI and collection of blood samples throughout the trial. Patients may also undergo tumor biopsy during screening and on study.
Procedure: Biopsy Procedure · Procedure: Biospecimen Collection · Procedure: Computed Tomography · Procedure: Echocardiography Test · Procedure: Magnetic Resonance Imaging · Procedure: Multigated Acquisition Scan · Drug: Neratinib Maleate
Patients receive neratinib maleate PO QD on days 1-14 of cycle 0 in the absence of disease progression or unacceptable toxicity. Patients then receive neratinib maleate PO QD on days 1-28 and palbociclib PO QD on days 1-21 of each subsequent cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO or MUGA during screening and on study, and CT or MRI and collection of blood samples throughout the trial. Patients may also undergo tumor biopsy during screening and on study.
Procedure: Biopsy Procedure · Procedure: Biospecimen Collection · Procedure: Computed Tomography · Procedure: Echocardiography Test · Procedure: Magnetic Resonance Imaging · Procedure: Multigated Acquisition Scan · Drug: Neratinib Maleate · Drug: Palbociclib
Patients receive paclitaxel IV on days 1, 8, and 15 and ipatasertib PO on days 1-21 of each cycle. Treatment repeats every 28 days for up to 35 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo a CT or MRI and blood collection throughout the trial. Patients also undergo a tumor biopsy during screening and optionally during follow-up.
Procedure: Biopsy Procedure · Procedure: Biospecimen Collection · Procedure: Computed Tomography · Drug: Ipatasertib · Procedure: Magnetic Resonance Imaging · Drug: Paclitaxel
Given PO
Also known as: BYL 719, BYL-719, BYL719, Phosphoinositide 3-kinase Inhibitor BYL719, Piqray, VIJOICE
Given PO
Also known as: ARRY 162, ARRY 438162, ARRY-162, ARRY-438162, ARRY162, ARRY438162, MEK 162, MEK-162, MEK162, Mektovi
Undergo biopsy
Also known as: Biopsy, BIOPSY_TYPE, Bx
Undergo blood collection
Also known as: Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection
Undergo bone marrow aspiration
Undergo bone marrow biopsy
Also known as: Biopsy of Bone Marrow, Biopsy, Bone Marrow
Undergo bone scan
Also known as: Bone Scintigraphy
Undergo 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
Undergo ECHO
Also known as: EC, Echocardiography
Given IV
Also known as: 5 Fluorouracil, 5 Fluorouracilum, 5 FU, 5-Fluoro-2,4(1H, 3H)-pyrimidinedione, 5-Fluorouracil, 5-Fluracil, 5-Fu, 5FU, AccuSite, Carac, Fluoro Uracil, Fluouracil, Flurablastin, Fluracedyl, Fluracil, Fluril, Fluroblastin, Ribofluor, Ro 2-9757, Ro-2-9757
Given IM
Also known as: Faslodex, Faslodex(ICI 182,780), ICI 182,780, ICI 182780, ICI-182780, ICI182780, ZD 9238, ZD-9238, ZD9238
Given PO
Also known as: GDC 0068, GDC-0068, GDC0068, RG 7440, RG-7440, RG7440
Given IV
Also known as: Folinic acid
Undergo 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
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
Undergo tumor mutational screening
Given PO
Also known as: 2-Butenamide, N-(4-((3-chloro-4-(2-pyridinylmethoxy)phenyl)amino)-3-cyano-7-ethoxy-6-quinolinyl)-4-(dimethylamino)-, (2E)-, (2Z)-2-butenedioate (1:1), HKI-272 Maleate, NERATINIB MALEATE ANHYDROUS, Nerlynx
Given PO
Also known as: AMN 107, AMN-107, AMN107, Nilotinib Monohydrochloride Monohydrate, Tasigna
Given PO
Also known as: AZD 2281, AZD-2281, AZD2281, KU 0059436, KU-0059436, KU0059436, Lynparza, Olanib, Olaparix, PARP Inhibitor AZD2281
Given IV
Also known as: 1-OHP, Ai Heng, Aiheng, Dacotin, Dacplat, Diaminocyclohexane Oxalatoplatinum, Eloxatin, Eloxatine, Elplat, JM 83, JM-83, JM83, Oxalatoplatin, Oxalatoplatinum, RP 54780, RP-54780, RP54780, SR 96669, SR-96669, SR96669
Given PO or IV
Also known as: Anzatax, Asotax, Bristaxol, Praxel, Taxol, Taxol Konzentrat
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
Given IV
Also known as: ABX-EGF, ABX-EGF Monoclonal Antibody, ABX-EGF, Clone E7.6.3, E7.6.3, Human IgG2K Monoclonal Antibody, MoAb ABX-EGF, MoAb E7.6.3, Monoclonal Antibody ABX-EGF, Monoclonal Antibody E7.6.3, Vectibix
Undergo PET
Also known as: Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure), Positron Emission Tomography Scan, Positron-Emission Tomography, PT
Given PO
Also known as: AZD-6244 Hydrogen Sulfate, AZD6244 Hydrogen Sulfate, AZD6244 Hydrogen Sulphate, Koselugo, Selumetinib Sulphate
Given PO
Also known as: AMG 510, AMG-510, AMG510, Lumakras, Lumykras
Accrual of patients to ComboMATCH treatment trials
Will be estimated over time and considered in relationship to changes in treatment trial cohort status (activations, suspensions, terminations).
Time frame: Up to 8 years
Assignment of patients to ComboMATCH treatment trials
Will be estimated over time and considered in relationship to changes in treatment trial cohort status (activations, suspensions, terminations).
Time frame: Up to 8 years
Enrollment rates to ComboMATCH treatment trials
Will be estimated over time and considered in relationship to changes in treatment trial cohort status (activations, suspensions, terminations).
Time frame: Up to 8 years
Rate of positive outcomes within the treatment trial defined cohorts
For each cohort in each treatment trial there is a defined primary efficacy endpoint (usually progression free survival \[PFS\] or overall response rate) and defined primary analysis for evaluating the primary endpoint. As cohorts are completed, whether they meet the criteria for a positive primary outcome will be determined. Positive treatment cohort outcome (on primary endpoint) will be analyzed as a binary random variable. The raw proportion of treatment cohorts with positive outcomes and an exact binomial confidence interval will be computed. If there are a sufficient number of treatment cohorts, logistic regression analysis will be performed examining the relationship of treatment cohort characteristics with successful outcomes. The goal is to achieve a rate of at least 30% with positive outcomes, both overall and in the subset of treatment trials based on in vivo models.
Time frame: Up to 8 years
Concordance between whole exome sequencing (WES) and results from the Designated Laboratory (DL)
Whole exome and other sequencing will be performed on mandatory tissue biopsies or, if no biopsy tissue is available, on submitted formalin-fixed paraffin-embedded tissue. These assays will be done in a clinical laboratory (e.g., Clinical Laboratory Improvement Act-compliant); but results will not be returned to the clinical site. Results will be used to compare with the DL assay results. This comparison will be required to conduct an important secondary analysis of the primary endpoint in each cohort in each treatment trial, restricting to those cases that are concordant between WES and the result from the DL that was the basis for enrollment (integrated).
Time frame: Up to 8 years
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Plan to share: Yes — NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.
Data sharing details ↗ · grants.nih.gov
No publications or documents are linked to this record.
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
Eligibility is decided by the study team. Share this record with your doctor or contact the team directly.
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Studies of the drugs tested here: Alpelisib · Binimetinib · Fluorouracil · Leucovorin · Neratinib · Nilotinib · Olaparib · Oxaliplatin · Paclitaxel · Palbociclib · Panitumumab · Selumetinib sulfate · Sotorasib
National Cancer Institute (NCI) →