Molecular Analysis for Therapy Choice (MATCH)
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 6,452
- 试验地点
- 2,703
- 主要终点
- Objective response rate (ORR)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Screening
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
- •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
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排除标准
- 未提供
研究组 & 干预措施
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.
干预措施: Cytology Specimen Collection Procedure (Other)
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.
干预措施: Laboratory Biomarker Analysis (Other)
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.
干预措施: Afatinib (Drug)
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.
干预措施: Laboratory Biomarker Analysis (Other)
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.
干预措施: Biopsy Procedure (Procedure)
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.
干预措施: Laboratory Biomarker Analysis (Other)
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.
干预措施: Crizotinib (Drug)
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.
干预措施: Cytology Specimen Collection Procedure (Other)
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.
干预措施: Radiologic Examination (Procedure)
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.
干预措施: Radiologic Examination (Procedure)
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.
干预措施: Cytology Specimen Collection Procedure (Other)
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.
干预措施: Laboratory Biomarker Analysis (Other)
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.
干预措施: Laboratory Biomarker Analysis (Other)
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.
干预措施: Cytology Specimen Collection Procedure (Other)
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.
干预措施: Biopsy Procedure (Procedure)
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.
干预措施: Laboratory Biomarker Analysis (Other)
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.
干预措施: Cytology Specimen Collection Procedure (Other)
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.
干预措施: Magnetic Resonance Imaging (Procedure)
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.
干预措施: Biospecimen Collection (Procedure)
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.
干预措施: Laboratory Biomarker Analysis (Other)
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.
干预措施: Biopsy Procedure (Procedure)
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.
干预措施: Computed Tomography (Procedure)
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.
干预措施: Cytology Specimen Collection Procedure (Other)
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.
干预措施: Biospecimen Collection (Procedure)
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.
干预措施: Laboratory Biomarker Analysis (Other)
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.
干预措施: Trastuzumab Emtansine (Biological)
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.
干预措施: Trametinib (Drug)
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.
干预措施: Cytology Specimen Collection Procedure (Other)
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.
干预措施: Laboratory Biomarker Analysis (Other)
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.
干预措施: Laboratory Biomarker Analysis (Other)
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.
干预措施: Cytology Specimen Collection Procedure (Other)
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.
干预措施: Laboratory Biomarker Analysis (Other)
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.
干预措施: Cytology Specimen Collection Procedure (Other)
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.
干预措施: Laboratory Biomarker Analysis (Other)
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.
干预措施: Computed Tomography (Procedure)
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.
干预措施: Defactinib (Drug)
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.
干预措施: Biospecimen Collection (Procedure)
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.
干预措施: Cytology Specimen Collection Procedure (Other)
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.
干预措施: Cytology Specimen Collection Procedure (Other)
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.
干预措施: Magnetic Resonance Imaging (Procedure)
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.
干预措施: Radionuclide Imaging (Procedure)
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.
干预措施: Laboratory Biomarker Analysis (Other)
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.
干预措施: Cytology Specimen Collection Procedure (Other)
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.
干预措施: Laboratory Biomarker Analysis (Other)
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.
干预措施: Cytology Specimen Collection Procedure (Other)
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.
干预措施: Laboratory Biomarker Analysis (Other)
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.
干预措施: Cytology Specimen Collection Procedure (Other)
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.
干预措施: Computed Tomography (Procedure)
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.
干预措施: Biospecimen Collection (Procedure)
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.
干预措施: Magnetic Resonance Imaging (Procedure)
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.
干预措施: Laboratory Biomarker Analysis (Other)
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.
干预措施: Copanlisib Hydrochloride (Drug)
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.
干预措施: Computed Tomography (Procedure)
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.
干预措施: Cytology Specimen Collection Procedure (Other)
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.
干预措施: Cytology Specimen Collection Procedure (Other)
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.
干预措施: Cytology Specimen Collection Procedure (Other)
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.
干预措施: Laboratory Biomarker Analysis (Other)
Subprotocol Z1K (AKT mutation)
Patients receive ipatasertib PO QD. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: Laboratory Biomarker Analysis (Other)
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.
干预措施: Cytology Specimen Collection Procedure (Other)
Subprotocol Z1K (AKT mutation)
Patients receive ipatasertib PO QD. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: Cytology Specimen Collection Procedure (Other)
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.
干预措施: Computed Tomography (Procedure)
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.
干预措施: Cytology Specimen Collection Procedure (Other)
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.
干预措施: Laboratory Biomarker Analysis (Other)
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.
干预措施: Cytology Specimen Collection Procedure (Other)
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.
干预措施: Laboratory Biomarker Analysis (Other)
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.
干预措施: Laboratory Biomarker Analysis (Other)
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.
干预措施: Biopsy Procedure (Procedure)
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.
干预措施: Biospecimen Collection (Procedure)
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.
干预措施: Laboratory Biomarker Analysis (Other)
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.
干预措施: Cytology Specimen Collection Procedure (Other)
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.
干预措施: Laboratory Biomarker Analysis (Other)
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.
干预措施: Biospecimen Collection (Procedure)
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.
干预措施: Cytology Specimen Collection Procedure (Other)
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.
干预措施: Cytology Specimen Collection Procedure (Other)
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.
干预措施: Laboratory Biomarker Analysis (Other)
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.
干预措施: Magnetic Resonance Imaging (Procedure)
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.
干预措施: Laboratory Biomarker Analysis (Other)
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.
干预措施: Laboratory Biomarker Analysis (Other)
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.
干预措施: Magnetic Resonance Imaging (Procedure)
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.
干预措施: Laboratory Biomarker Analysis (Other)
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.
干预措施: PI3K-beta Inhibitor GSK2636771 (Drug)
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.
干预措施: Laboratory Biomarker Analysis (Other)
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.
干预措施: Laboratory Biomarker Analysis (Other)
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.
干预措施: Biopsy Procedure (Procedure)
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.
干预措施: Cytology Specimen Collection Procedure (Other)
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.
干预措施: Laboratory Biomarker Analysis (Other)
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.
干预措施: Cytology Specimen Collection Procedure (Other)
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.
干预措施: Cytology Specimen Collection Procedure (Other)
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.
干预措施: Laboratory Biomarker Analysis (Other)
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.
干预措施: Adavosertib (Drug)
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.
干预措施: Taselisib (Drug)
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.
干预措施: Copanlisib Hydrochloride (Drug)
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.
干预措施: Copanlisib (Drug)
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.
干预措施: Palbociclib (Drug)
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.
干预措施: Palbociclib (Drug)
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.
干预措施: Erdafitinib (Drug)
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.
干预措施: Nivolumab (Biological)
Subprotocol Z1K (AKT mutation)
Patients receive ipatasertib PO QD. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: Ipatasertib (Drug)
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.
干预措施: Biopsy Procedure (Procedure)
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.
干预措施: Cytology Specimen Collection Procedure (Other)
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.
干预措施: Echocardiography Test (Procedure)
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.
干预措施: Copanlisib Hydrochloride (Drug)
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.
干预措施: Nivolumab (Biological)
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.
干预措施: Biopsy Procedure (Procedure)
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.
干预措施: Cytology Specimen Collection Procedure (Other)
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.
干预措施: Laboratory Biomarker Analysis (Other)
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.
干预措施: Cytology Specimen Collection Procedure (Other)
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.
干预措施: Biospecimen Collection (Procedure)
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.
干预措施: Trametinib (Drug)
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.
干预措施: Echocardiography Test (Procedure)
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.
干预措施: Crizotinib (Drug)
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.
干预措施: Vismodegib (Drug)
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.
干预措施: Radiologic Examination (Procedure)
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.
干预措施: Biopsy Procedure (Procedure)
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.
干预措施: Biospecimen Collection (Procedure)
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.
干预措施: Trametinib (Drug)
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.
干预措施: Pertuzumab (Biological)
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.
干预措施: Ulixertinib (Drug)
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.
干预措施: Sapanisertib (Drug)
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.
干预措施: Laboratory Biomarker Analysis (Other)
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.
干预措施: Biopsy Procedure (Procedure)
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.
干预措施: Biospecimen Collection (Procedure)
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.
干预措施: Cytology Specimen Collection Procedure (Other)
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.
干预措施: Echocardiography Test (Procedure)
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.
干预措施: Biospecimen Collection (Procedure)
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.
干预措施: Computed Tomography (Procedure)
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.
干预措施: Cytology Specimen Collection Procedure (Other)
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.
干预措施: Magnetic Resonance Imaging (Procedure)
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.
干预措施: Trametinib (Drug)
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.
干预措施: Copanlisib (Drug)
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.
干预措施: Copanlisib (Drug)
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.
干预措施: Laboratory Biomarker Analysis (Other)
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.
干预措施: Biopsy Procedure (Procedure)
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.
干预措施: Dasatinib (Drug)
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.
干预措施: Afatinib (Drug)
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.
干预措施: Crizotinib (Drug)
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.
干预措施: Afatinib Dimaleate (Drug)
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.
干预措施: Afatinib Dimaleate (Drug)
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.
干预措施: Cytology Specimen Collection Procedure (Other)
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.
干预措施: Multigated Acquisition Scan (Procedure)
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.
干预措施: Cytology Specimen Collection Procedure (Other)
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.
干预措施: Radionuclide Imaging (Procedure)
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.
干预措施: Cytology Specimen Collection Procedure (Other)
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.
干预措施: Biopsy Procedure (Procedure)
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.
干预措施: Laboratory Biomarker Analysis (Other)
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.
干预措施: Laboratory Biomarker Analysis (Other)
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.
干预措施: PI3K-beta Inhibitor GSK2636771 (Drug)
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.
干预措施: Sapanisertib (Drug)
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.
干预措施: Defactinib Hydrochloride (Drug)
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.
干预措施: Dabrafenib Mesylate (Drug)
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.
干预措施: Osimertinib (Drug)
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.
干预措施: Crizotinib (Drug)
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.
干预措施: Larotrectinib (Drug)
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.
干预措施: Erdafitinib (Drug)
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.
干预措施: Relatlimab (Biological)
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.
干预措施: Laboratory Biomarker Analysis (Other)
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.
干预措施: Magnetic Resonance Imaging (Procedure)
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.
干预措施: Cytology Specimen Collection Procedure (Other)
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.
干预措施: Trastuzumab (Biological)
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.
干预措施: Capivasertib (Drug)
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.
干预措施: Cytology Specimen Collection Procedure (Other)
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.
干预措施: Echocardiography Test (Procedure)
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.
干预措施: Binimetinib (Drug)
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.
干预措施: Computed Tomography (Procedure)
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.
干预措施: Echocardiography Test (Procedure)
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.
干预措施: Fexagratinib (Drug)
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.
干预措施: Larotrectinib Sulfate (Drug)
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.
干预措施: Radionuclide Imaging (Procedure)
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.
干预措施: Sunitinib Malate (Drug)
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.
干预措施: Radiologic Examination (Procedure)
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.
干预措施: Trastuzumab (Biological)
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.
干预措施: Dabrafenib (Drug)
结局指标
主要结局
Objective response rate (ORR)
时间窗: Up to 3 years
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)
次要结局
- Overall survival (OS)(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(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(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)