CD4 counts: \r\n* For Stratum 1: CD4+ cell count greater than 200 cells/mm^3 obtained within 2 weeks prior to enrollment at any United States (U.S.) laboratory that has a clinical laboratory improvement amendments (CLIA) certification or its equivalent\r\n* For Stratum 2: CD4 cell count between 100-200 cells/mm^3 obtained within 2 weeks prior to enrollment at any U.S. laboratory that has a clinical laboratory improvement amendments (CLIA) certification or its equivalent\r\n* Expansion Cohort: CD4 cell count for this cohort will be specified once Stratum 1 and Stratum 2 have completed enrollment\r\n* Solid Tumor Expansion Cohort: CD4+ cell count greater than 200 cells/mm^3 obtained within 2 weeks prior to enrollment at any U.S. laboratory that has a clinical laboratory improvement amendments (CLIA) certification or its equivalent\r\n* cHL Cohort: CD4 cell count of at least 100 cells/mm^3
Patient must have TCCs tumors harboring a TSC1 or TSC2 mutation identified by a Clinical Laboratory Improvement Amendments (CLIA) certified laboratory
Previously registered to A151216, with the result of lung cancer harboring an EGFR exon 19 deletion or L858R mutation; the testing must have been performed by one of the following criteria:\r\na) Patient registered to A151216 and the assessment performed centrally by the protocol-specified laboratory\r\nb) By a local Clinical Laboratory Improvement Amendments (CLIA) certified laboratory; the report must indicate the result as well as the CLIA number of the laboratory that performed the assay; these patients will also have been registered to A151216, but can be enrolled on A081105 regardless of the central lab results\r\n* Patients with known resistant mutations in the EGFR tyrosine-kinase (TK) domain (T790M) are not eligible\r\n* Patients that are both EGFR mutant and anaplastic lymphoma kinase (ALK) rearrangements will be registered to A081105
Tissue must have been determined to have local 1p/9q co-deletion and IDH mutation prior to submission for central path review\r\n* Tumor tissue must show co-deletion of chromosomes 1p and 19q; for eligibility, the 1p/19q analysis results will be accepted from the local site, as determined by either a locally available or reference laboratory (for US, must be Clinical Laboratory Improvement Act [CLIA] certified); acceptable methods for determination of 1p/19q loss include fluorescent in-situ hybridization (FISH), by genomic sequencing or methylomic analyses; US and Canadian sites must send a copy of the official report to the pathology coordinator and quality assurance specialist (QAS)\r\n* Tumor must also show evidence of IDH mutation by immunohistochemistry or genomic analyses; this should be performed at the local site (US: performed in a CLIA certified laboratory); the site must send a copy of the official report to the pathology coordinator and QAS
Histologically confirmed UC of the bladder, urethra, ureter or renal pelvis with positive retinoblastoma (Rb+)/CDKN2A- based on immunohistochemistry (IHC) of tissue blocks or unstained slides performed within a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory at University of North Carolina (UNC); if stage I of original cohort indicates futility, molecular requirement for eligibility will change to Rb+/CCND1 overexpression (also based on IHC)
Pretreatment cytogenetics must be performed on all patients; collection of pretreatment specimens must be completed within 14 days prior to registration to S1312; specimens must be submitted to the site's preferred Clinical Laboratory Improvement Amendments (CLIA)-approved cytogenetics laboratory; reports of the results must be submitted as described; note that cytogenetics are required at other time points
Formalin fixed paraffin embedded tumor tissue (preferably from the most recent recurrence) must be available to assess Rb1 protein status prior to enrollment on phase I or surgical study; if the subject has results from prior Rb1 IHC testing in a Clinical Laboratory Improvement Act (CLIA)-certified laboratory the requirement for screening to assess Rb1 protein status is waived; in these cases, patients will not be required to sign a screening consent
PHASE I (STRATUM 1): Patient has intact Rb1 protein confirmed either from previous results or screened tissue; all testing must be performed in a CLIA certified laboratory; DIPG patients with radiographically typical appearance will be waived from this requirement
All patients with breast and gastric/gastroesophageal junction cancers should have HER2 testing performed using a FDA approved test in a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory.
Pathologically confirmed recurrent or metastatic advanced solid tumor, for which there is no curative-intent treatment option and confirmation of the presence of AKT1, AKT2, or AKT3 mutations detected by the Memorial Sloan-Kettering (MSK)-integrated mutation profiling of actionable cancer targets (IMPACT) assay platform or other Clinical Laboratory Improvement Act (CLIA)-approved test
Participants must have PD-L1 IHC testing with results performed by a central laboratory during the screening period
HER2 positive patients by local laboratory testing.
Presence of alteration in CDK pathway (amplifications in CDK4, CDK6, CCND1, CCND2, CCND3 or CCNE1 or loss of CDKN2A) using a Clinical Laboratory Improvement Act (CLIA)-certified assay
Molecular testing results from Clinical Laboratory Improvement Amendments (CLIA)-certified laboratories used for patient eligibility should be obtained from the most recent tumor biopsy (baseline tumor biopsies and on-progression tumor biopsies are optional)
Participants must have histologically confirmed advanced malignancy that is metastatic and/or unresectable and/or recurrent with confirmed inactivating mutations in TSC1 or TSC2 or activating MTOR mutations, identified in any Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory; all genetic findings must be reviewed by the study principal investigator (PI), Dr. David Kwiatkowski, prior to study entry
Uric acid if elevated, corrected to within laboratory range prior to dosing
Molecular confirmation of a RET translocation is required to begin protocol therapy; methods of acceptable molecular confirmation include RET fluorescent in situ hybridization (FISH) and next-generation sequencing performed in a Clinical Laboratory Improvement Amendment (CLIA) certified lab
Uric acid must be within laboratory normal range
For enrollment to arm 1: participants must have a confirmed CCND1, 2, or 3 high-level amplification, CCND1 mutation, or a CCND1 splice variant expected to lead to nuclear retention of cyclin D1 protein, via Dana-Farber Cancer Institute (DFCI)/Brigham and Women's Hospital (BWH) OncoPanel or any Clinical Laboratory Improvement Act (CLIA)-certified method
MYD88 and CXCR4 mutated disease (determined by Treon laboratory or molecular diagnostics laboratory)
ENROLLMENT TO THE DOSE ESCALATION, EXPANSION AND PART II: Participants must have histologically confirmed advanced NSCLC (with a confirmed KRAS mutation via any Clinical Laboratory Improvement Act [CLIA]-certified method) for which curable treatment modalities are not an option
Adequate laboratory results including the following:
Histologic proof of melanoma reviewed and confirmed by the treating institution; the melanoma must have a documented BRAF V600E or BRAF V600K mutation by genotyping or immunohistochemistry (IHC) 12 performed by a Clinical Laboratory Improvement Act (CLIA) certified laboratory; at Memorial Sloan-Kettering (MSK), the diagnostic molecular pathology laboratory has developed and implemented a targeted capture-based next-generation deoxyribonucleic acid (DNA) sequencing assay, MSK-integrated mutation profiling of actionable cancer targets (IMPACT), to profile all protein-coding exons and selected introns from 410 oncogenes and tumor suppressor genes in formalin-fixed paraffin embedded tissues; MSK-IMPACT has been approved by the New York (NY) State Department of Health to be run as a clinical assay in the CLIA-compliant diagnostic molecular pathology laboratory; MSK-IMPACT is capable of detecting mutations, copy number alterations, and structural variations; BRAF exon15 was captured by the MSK-IMPACT panel and the c.1799T>A (p.V600E) mutation was fully validated as per New York State (NYS) requirements; detailed results of the validation of this mutation were included in the validation package submitted to NY State Department of Health
Molecular testing results from clinical laboratory improvement amendments (CLIA)-certified laboratories (using tissue and/or blood) demonstrating HER2 overexpression or amplification. Participants must have one of the following tumor types: biliary cancer, salivary cancer, or bladder cancer. a) For participants screened using a blood assay: obtain tissue-based testing result confirming study eligibility (within first 4 weeks after enrollment)
Molecular testing results from CLIA-certified laboratories (using tissue and/or blood) demonstrating EGFR-activating mutations Vemurafenib plus Cobimetinib
All therapy should be dispensed at the primary institution; we encourage all imaging studies to be reviewed and reported by the primary institution; laboratory studies may be performed at a Clinical Laboratory Improvement Act (CLIA)-certified laboratory of the investigator’s choice
INCLUSION CRITERIA FOR REGISTRATION (HER2 MUTATION IDENTIFIED AT AN OUTSIDE CLINICAL LABORATORY IMPROVEMENT ACT [CLIA] CERTIFIED LOCATION): Histologically or cytologically confirmed HER2-negative (0 or 1+ by IHC or non- amplified by FISH) breast cancer that is stage IV
Stratum A: Newly diagnosed children (3-21 years old) with DIPG who are positive for the H3.3K27M mutation (positive testing in Clinical Laboratory Improvement Act [CLIA] laboratory) that underwent standard radiation therapy
Stratum B: Newly diagnosed children (3-21 years old) with diagnosis of glioma other than DIPG who are positive for the H3.3K27M mutation (positive testing in CLIA laboratory) including spinal cord gliomas that underwent standard radiation therapy
Participants enrolling into the MET cohort must have a MET exon 14 mutation as confirmed by targeted next generation (NextGen) sequencing using the Dana-Farber Cancer Institute (DFCI)/Brigham and Women’s Hospital (BWH) OncoPanel or another Clinical Laboratory Improvement Act (CLIA)-certified method; participants whose NSCLC specimens contain actionable genetic mutations/alterations (e.g. ALK/EGFR) should receive appropriate targeted therapies prior to enrollment in the trial
PROCUREMENT INCLUSION: CD30 positive tumor as assayed in a Clinical Laboratory Improvement Act (CLIA) certified pathology laboratory (result can be pending at this time)
TREATMENT INCLUSION: CD30-positive tumor as assayed in a CLIA certified pathology laboratory
Tumor positive for EBV encoded RNA (EBER) based on report from certified laboratory.
Any isolated laboratory abnormality suggestive of a serious autoimmune disease (e.g. hypothyroidism)
Acceptable laboratory results
Patients must have available tumor molecular profiling from Clinical Laboratory Improvement Amendments (CLIA)-certified labs or have available archived tissue to be sent to such a laboratory in the context of this investigation
Molecular testing in a CLIA-certified laboratory must have demonstrated a deletion involving the CDKN2A locus or a mutation within the locus that can be deemed from best available evidence to be likely to cause inactivation of a gene within or protein encoded by CDKN2A; sequencing or fluorescence in situ hybridization (FISH)/chromogenic in situ hybridization (CISH) methods are acceptable; the investigators will consider analyses performed according to similar standards as applied by Foundation Medicine (likely to be the most common source of molecular diagnostic data for patients in this trial)
Laboratory requirements:
Patients must have positive genetic testing for NF1 in a Clinical Laboratory Improvement Amendments (CLIA) certified laboratory or a diagnosis of NF1 based on clinical National Institutes of Health (NIH) consensus criteria of at least one other diagnostic criterion in addition to the presence of a PN; NF1 mutation analysis will be performed on germline deoxyribonucleic acid (DNA) as described by Messiaen & Wimmer; histologic confirmation of tumor is not necessary in the presence of consistent clinical and imaging findings, but should be considered if malignant transformation of a PN is clinically suspected; additional criteria are as follows:\r\n* Six or more cafe-au-lait macules (>= 0.5 cm in prepubertal subjects or >= 1.5 cm in post pubertal subjects)\r\n* Freckling in axilla or groin\r\n* Optic glioma\r\n* Two or more Lisch nodules\r\n* A distinctive bony lesion (dysplasia of the sphenoid bone or dysplasia or thinning of long bone cortex)\r\n* A first-degree relative with NF1
INCLUSION CRITERIA FOR STRATUM C: Diagnosis of hypermutated brain tumors\r\nPatients with brain tumors and increased tumor mutation burden as determined by\r\n* Confirmed diagnosis of CMMRD syndrome by Clinical Laboratory Improvement Act (CLIA)-certified germline gene sequencing OR\r\n* Confirmation of high mutation burden by whole genome/exome sequencing performed in a CLIA-certified laboratory and/or the use of Foundation One next generation sequence panel or another CLIA approved targeted sequencing lab with publicly available correlations between number of mutations found in the panel and mutations per megabase and/or genome; for protocol purposes a high mutation burden will be defined as at least 100 non-synonymous coding-region mutations by whole exome/genome sequencing (well above two standard deviations of the number of median similar mutations described in pediatric CNS cancers) AND/OR a high tumor mutation burden (TMB) or intermediate TMB based on the reporting parameters of the panel; TMB parameters provided for the Foundation One reports are high tumor mutation burden is >= 20 mutations per megabase or intermediate TMB is between 6 to 19 mutations per megabase\r\n* Confirmed diagnosis of Lynch syndrome by CLIA-certified germline gene sequencing; patients with Lynch syndrome will not be accounted for in primary objective unless their tumors are determined to have the minimum number of mutations described above but they will still be eligible for this study\r\n* Low-grade tumors in patients with CMMRD or Lynch syndrome do not have to reach the threshold of 100 mutations for study inclusion
A documented deleterious gBRCA1/2m obtained in a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory, including but not limited to Myriad Genetics, either by multi-gene panels or individual testing, for cohort 1 patients prior to study enrollment; variants of uncertain significance (VUS) of BRCA1/2 are not considered deleterious; patients with VUS or deleterious mutation in other genes without gBRCA1/2m can be considered for cohort 2 or 3 or 5
Patients must have tumor evidence of somatic genomic molecular alteration in EGFR, HER2, ERBB3, or ERBB4, from a test result generated in a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory; the tumor tissue sample used to generate the qualifying report must be from a muscle-invasive or higher stage urinary tract cancer specimen (metastatic tissue is also acceptable); final determination about whether a specific tissue source or molecular genomic finding meets criteria as a qualifying result rests with the central study principal investigator (PI)
For patients with metastatic colorectal cancer:\r\n* Stage IV histologically-proven colorectal adenocarcinoma\r\n* Liver metastasis confirmed to be surgically resectable, with surgery evaluation and planned resection; may have minimal extrahepatic disease that is determined to be resectable\r\n* Tumor must be confirmed to be microsatellite stable (MSS); if not already reported at a Clinical Laboratory Improvement Act (CLIA)-certified laboratory, we will be able to perform this at Emory University\r\n* No prior immunotherapy\r\n* No cancer chemotherapy treatment 2 weeks prior to day 1 of treatment
Known mutation of the IDH1 or IDH2 genes in the tumor\r\n* Documentation that no IDH1 or IDH2 mutations are present in the tumor by a Clinical Laboratory Improvement Amendments (CLIA) approved laboratory is required prior to initiation of study treatment
Participants must have a genomic (DNA and/or ribonucleic acid [RNA]) alteration (mutation, fusion, and/or amplification) involving PDGF-A, PDGF-B, PDGFR-A, PDGFR-B, FGF1, FGF3, FGFR1 or FGFR3, as identified by tumor (formalin-fixed, paraffin-embedded [FFPE] or fresh, diagnosis or relapse tissue, but relapse tissue preferred) sequencing; sequencing will be performed through the University of Michigan MI-ONCOSEQ study (Clinical Laboratory Improvement Act [CLIA]-certified), or other (non-university [U] of Michigan) CLIA-certified tumor DNA or RNA sequencing
Patients who are HIV positive (by self-report) or have clinical or laboratory features indicative of AIDS.
Adequate laboratory results including the following:
Patients must meet at least one of the following AVPC criteria: \r\n* Histologically proven small cell (neuroendocrine) prostate carcinoma.\r\n* Exclusive visceral metastases. \r\n* Predominantly lytic bone metastases identified by plain x-ray or CT scan. \r\n* Bulky (>= 5 cm in longest dimension) lymphadenopathy or high-grade tumor mass in prostate/pelvis. \r\n* Low PSA (=< 10 ng/mL) at initial presentation (prior to androgen ablation or at symptomatic progression in the castrate-setting) plus high volume (>= 20) bone metastases. \r\n* Elevated serum lactate dehydrogenase (>=2 x upper limit of normal) or elevated serum carcinoembryonic antigen (>= 2 x upper limit of normal) in the absence of other etiologies. \r\n* Short interval (=< 180 days) to castrate-resistant progression following initiation of hormonal therapy. \r\n* Known loss or mutation (by Clinical Laboratory Improvement Act [CLIIA] certified molecular testing, immunohistochemistry staining method [IHC] and/or DNA sequencing) in at least 2 of the following: Tp53, RB1 and PTEN.
Documented non-synonymous somatic mutation in NF1 in any tumor specimen or cell-free DNA assay by Clinical Laboratory Improvement Act (CLIA)-approved laboratory
PTEN or PIK3CB mutated advanced solid tumor\r\n* PTEN loss of function mutation or PIK3CB gain of function mutation identified by local Clinical Laboratory Improvement Act (CLIA) certified next generation sequencing (NGS)\r\n* Breast cancers patients enrolled on this study must have either:\r\n** Estrogen receptor positive and HER2 negative breast cancer\r\n** Triple negative breast cancer
Patients must have vulvar HSIL as confirmed by pathology report from a Clinical Laboratory Improvement Act (CLIA)-certified laboratory
Measurable metastatic or unresectable malignancy expressing G12V mutated KRAS as assessed by one of the following methods: reverse transcriptase-polymerase chain reaction (RT-PCR) on tumor tissue, tumor deoxyribonucleic acid (DNA) sequencing or any other Clinical Laboratory Improvement Act (CLIA) certified laboratory test on resected tissue; patients shown to have tumors expressing G12V mutated NRAS and HRAS will also be eligible
Have one of the following confirmed histologically, cytologically, or through biochemical testing:\r\n* Wild-type GIST (GIST without KIT or PDGFRA mutation);\r\n* PHEO/PGL with a germline mutation in SDHA, SDHB, SDHC, or SDHD;\r\n* Renal cell cancer associated with HLRCC\r\n* Testing will be performed in Clinical Laboratory Improvement Act (CLIA) certified labs using genetic tests for KIT/PDGFRA and testing panels developed for patients with PHEO/PGL; results from outside labs will be accepted; pathologic diagnosis will be reviewed and verified at the Clinical Center
Patients must have histologically confirmed adenocarcinoma of the colon that has metastasized (stage 4) and is TP53 mutant/deleted by a Clinical Laboratory Improvement Act (CLIA) approved genetic test; only known loss of function TP53 mutation/deletion will be eligible for this study
Any of the following clinical laboratory results during screening (i.e., within 28 days before the first dose of study treatment):
Must have either a clinical diagnosis of NF1 or a germline NF1 mutation, or in patients without the NF1 syndrome, demonstrate an NF1 mutation in the GIST verified in a Clinical Laboratory Improvement Act (CLIA) certified laboratory; in patients without the NF1 syndrome, confirmation of the NF1 mutation in the GIST is required for enrollment
Patients must have a histologically or cytologically confirmed measurable GIST without platelet-derived growth factor receptor, alpha polypeptide (PDGFRA) or KIT proto-oncogene receptor tyrosine kinase (KIT) mutations; GIST may be newly diagnosed or recurrent provided that it meets criteria for progressive or metastatic disease; metastatic disease refers to disease outside the gastrointestinal (GI) tract, not simply a multifocal primary tumor; testing performed by the Laboratory of Pathology, National Cancer Institute (NCI), unless previously conducted by a CLIA/College of American Pathologists (CAP) external laboratory; analysis will include evaluation of 4 exons of KIT (9, 11, 13, 17) and 3 exons of PDGFRA (12, 14, 18)
Molecular identification of a KRAS mutation (codons 12, 13, or 61 mutations detected by sequencing) by a Clinical Laboratory Improvement Amendments (CLIA)-certified assay (source documentation required)
Documented evidence of an ALK rearrangement (by fluorescence in situ hybridization [FISH], immunohistochemistry [IHC], or next generation sequencing [NGS]), ROS1 rearrangement (by FISH or NGS), or MET oncogene as defined by MET exon 14 skipping (NGS), MET Y1003X mutation or MET gene fusion (NGS) in NSCLC tumor specimen by a Clinical Laboratory Improvement Act (CLIA)-approved laboratory
Documented ALK-rearrangement (or ROS1 rearrangement for phase I only) break-apart fluorescence in situ hybridization (FISH) (in >= 15% or tumor cells), or next generation sequencing assay performed on tumor sample or cell-­free DNA in Clinical Laboratory Improvement Amendments (CLIA)-approved laboratory
Laboratory requirements:
Patients who are HIV positive (by self-report) or have clinical or laboratory features indicative of AIDS.
Have all of the following results as part of screening laboratory assessments (results from either the central laboratory or a local laboratory can be used for qualification):
Previously obtained tumor sample exhibits a hypermutator phenotype; for the purposes of this trial, a hypermutator phenotype is defined as tumors harboring >= 30 mutations (non-synonymous somatic point or indel mutations) detected by the Memorial Sloan Kettering (MSK)-Integrated Mutation Profiling for Actionable Cancer Targets (IMPACT) or comparable next generation sequencing performed in a Clinical Laboratory Improvement Act (CLIA) environment; contingent to approval by the MSK principal investigator, patients with less than 30 mutations may be eligible if they display a mutation in a mismatch repair gene or other mutations in genes known to be associated with hypermutator phenotypes or microsatellite instability, including but not limited to MutL homolog (MLH)1, MutS protein homolog (MSH)2, MSH6, PMS2 postmeiotic segregation increased 2 (S. cerevisiae) (PMS)2, polymerase (deoxyribonucleic acid [DNA] directed), epsilon-1 (POLE), polymerase (DNA directed), delta 1, catalytic subunit (POLD) as determined by validated methods, or if microsatellite instability is present, as identified by polymerase chain reaction (PCR) or other validated methods\r\n* Note: the MSK-IMPACT (Integrated Mutation Profiling for Actionable Cancer Targets) assay is a next generation genomic profiling performed on formalin-fixed, paraffin-embedded (FFPE) tumor tissue in a CLIA-certified Molecular Diagnostic Service laboratory; IMPACT provides full exon coverage of 410 cancer related genes and can detect base substitutions, small indels, copy number alterations and selected gene re-rearrangements; in some cases, additional assays such as Sanger sequencing or fluorescence in situ hybridization (FISH) may be required to confirm specific results detected on IMPACT; patients at MSK will have this assay to determine eligibility; use of other validated next-generation sequencing techniques for eligibility may be considered, provided they are performed in a CLIA-certified laboratory and are approved by the MSK principal investigator
PHASE II: Patients must have histologically or cytologically confirmed, PIK3CA mutant metastatic colorectal cancer; PIK3CA status must be confirmed by tumor sequencing conducted in a Clinical Laboratory Improvement Act (CLIA) certified lab
Patients must have a documented germline neurofibromatosis 1 (NF1) mutation in a Clinical Laboratory Improvement Act (CLIA) certified laboratory or a diagnosis of NF1 based on clinical National Institutes of Health (NIH) consensus criteria; in addition to substantial cutaneous neurofibroma burden, at least one of the criteria below have to be present:\r\n* Six or more cafe-au-lait macules (>= 0.5 cm in prepubertal subjects or >= 1.5 cm in post pubertal subjects)\r\n* Freckling in axilla or groin\r\n* Optic glioma\r\n* Two or more Lisch nodules\r\n* A distinctive bony lesion (dysplasia of the sphenoid bone or dysplasia or thinning of long bone cortex)\r\n* A first-degree relative with NF1
PHASE II SCLC: Patients must have histologically or cytologically confirmed diagnosis of SCLC from a Clinical Laboratory Improvement Act (CLIA)-certified laboratory
mCRPC EXPANSION COHORT: Documented histopathological confirmation of prostate cancer from a CLIA- certified laboratory
Androgen receptor will be quantified using a Clinical Laboratory Improvement Act (CLIA)-compliant assay for AR on a biopsy specimen obtained prior to the start of treatment; AR-positivity is defined as >= 10% of nuclear staining
For cohort 1, documented activating HER2 mutation in lung cancer by Clinical Laboratory Improvement Act (CLIA) laboratory, specifically exon 20 insYVMA (Y772 A775dup), insGSP (G778 P780dup), insTGT (G776delinsVC), single base pair substitutions L 755A, L755S, V777L, V659E S310F, or another HER2 mutation approved by the principal investigator
For cohorts 2, 3, 4, documented HER2 amplification identified through next generation sequencing by Memorial Sloan-Kettering Cancer Center (MSK)-Integrated Mutation Profiling for Actionable Cancer Targets (IMPACT) or at another Clinical Laboratory Improvement Amendments (CLIA) laboratory, or documented HER2 amplification by in-situ hybridization (ISH) with HER2/ centromeric probe for chromosome 17 (CEP17) ratio >= 2.0 at a CLIA laboratory; patients with HER2 amplification identified by another method or criteria must be approved by the principal investigator and may enroll in the “other” cohort 4
Documented histopathological confirmation of prostate cancer from a Clinical Laboratory Improvement Act (CLIA)-certified laboratory
CAPMATINIB INCLUSION CRITERIA: Presence of an oncogenic kinase fusion involving MET, confirmed by assay by a Clinical Laboratory Improvement Act (CLIA)-approved laboratory
REGORAFENIB INCLUSION CRITERIA: Presence of an oncogenic kinase fusion involving BRAF or RET, confirmed by assay by a CLIA-approved laboratory
ENTRECTINIB INCLUSION CRITERIA: Presence of an oncogenic kinase fusion involving ROS1 or NTRK1/2/3, confirmed by assay by a CLIA-approved laboratory
Tumor must have labeling index of greater than or equal to 5% of the nuclear Gli-1 (integral biomarker performed in the MD Anderson Cancer Center Clinical Laboratory Improvement Amendment [CLIA] laboratory) for patient to be eligible in this trial (if enough archival tissue is not available to determine labeling index, patient must agree to a biopsy to be eligible for the study)
Has a documented local diagnostic pathology of original biopsy confirmed by a Clinical Laboratory Improvement Amendments (CLIA/College of American Pathologists (CAP) or equivalent laboratory certification
Patients must have CDKN2A-deficient tumor (deletion or mutation); definition of CDKN2A deficient tumor:\r\n* CDKN2A deletion or mutation by any Clinical Laboratory Improvement Amendments (CLIA)-certified sequencing OR\r\n* >= 30% of tumor cells with (at least) hemizygous deletion by fluorescent in situ hybridization (FISH); status will be determined from archived tissue
Patients with CDKN2A wild type by a CLIA-certified laboratory
Histologically confirmed diagnosis of advanced (metastatic or unresectable) NSCLC with mutations, rearrangement and fusion involving RET oncogene, or abnormalities (non-synonymous single nucleotide variant [SNV] or amplification) in the nintedanib target genes VEGFR1-3, TP53, PDGFR-A, PDGFR-B, or FGFR1-3; Clinical Laboratory Improvement Act (CLIA) certified lab testing for nintedanib target genes using cell free DNA from peripheral blood and/or assays performed on tumor tissues are acceptable
Patients must have activating genomic alterations in FGFR (mutations, fusions or amplifications [> 6 copies]) or activating genomic alterations in mast/stem cell growth factor receptor kit (KIT), platelet-derived growth factor receptor alpha (PDGFR alpha), ret proto-oncogene (RET), ABL proto-oncogene 1, non-receptor tyrosine kinase (ABL1) and fms-related tyrosine kinase 3 (FLT3) by any validated Clinical Laboratory Improvement Amendments (CLIA)-certified molecular testing (fluorescent in situ hybridization [FISH], polymerase chain reaction [PCR] or sequencing data are acceptable); CLIA validated results from other institutions; diagnostic labs (e.g. foundation medicine) are acceptable
BRAF mutation-positive melanoma (V600E or V600K) based on report from a Clinical Laboratory Improvement Amendments (CLIA) certified laboratory
COHORT A: Confirmation in a Clinical Laboratory Improvement Amendments (CLIA) certified laboratory that one of the patient’s thyroid tumors (primary tumor, recurrent tumor, or metastasis) has an neuroblastoma RAS viral (v-ras) oncogene homolog (NRAS) or Kirsten rat sarcoma viral oncogene homolog (KRAS) or Harvey rat sarcoma viral oncogene homolog (HRAS) mutation at G12, G13, or Q61; this group of patients will also be referred to as “RAS MUT”
Have clinically acceptable laboratory screening results within certain limits
RECIPIENT: Mutation in the GATA2 gene, or evidence of loss of expression of one allele of GATA2, by complementary deoxyribonucleic acid (cDNA) analysis performed by a Clinical Laboratory Improvement Amendments (CLIA) certified laboratory, or the clinical syndrome of MonoMAC
Patients must have a tissue or blood proven KRAS or EGFR mutation confirmed in a Clinical Laboratory Improvement Amendments (CLIA) certified lab (only required in the Phase IB expansion cohort)
Required baseline laboratory data
Diagnosis of dyskeratosis congenita based on clinical triad of abnormalities of skin pigmentation, nail dystrophy, oral leukoplakia; OR one of clinical triad and presence of two or more associated features; OR a pathogenic mutation in DKC1,TERC, TERT, NOP10, NHP2, TCAB1, TINF2, CTC1, PARN, RTEL1, or ACD as reported by a CLIA-approved laboratory; OR age-adjusted mean telomere length < 1%ile in peripheral blood lymphocytes as reported by a CLIA-approved laboratory; OR Hoyeraal-Hreidarsson syndrome; OR Revesz syndrome
FA demonstrated by a positive test for increased sensitivity to chromosomal breakage with mitomycin C or diepoxybutane performed by a Clinical Laboratory Improvement Amendments (CLIA) or College of American Pathologists (CAP) approved laboratory
DOCK8 deficiency with the two criteria listed below:\r\n* Clinical history of one or more episodes of life-threatening or severely disfiguring infection with opportunistic organisms, including severe recurrent cutaneous and sinopulmonary infections with bacterial or fungal infection, or viral infections with herpes simplex, herpes zoster, Molluscum contagiosum, or human papilloma virus\r\n* Homozygous or compound heterozygous mutations in the DOCK8 gene performed by a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory
Subject must meet all of the following criteria based on the centrally analyzed laboratory tests within 14 days prior to the first dose of study treatment. In case of multiple laboratory data within this period, the most recent data should be used to determine eligibility.
Required baseline central laboratory data in protocol.
Cancer must have at least one of the following PIK3CA mutations: E542K, E545K, H1047R, H1047L; the PIK3CA mutation must be documented in a Clinical Laboratory Improvement Amendments (CLIA) approved laboratory
Laboratory data:
Liver function status Child-Pugh (CP) Class A. CP status should be calculated based on clinical findings and laboratory results during the screening period.
Patients must have one of the histologically advanced solid tumors harboring CCNE1 amplification: their diseases are refractory to, or do not have, standard-of-care therapy; or they declined standard-of-care therapy; patients with triple negative breast cancer or small cell lung cancer are not eligible since there is an ongoing phase Ib study of AZD1775 as a single agent targeting these patients; CCNE1 amplification is defined in a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory: CCNE1 amplification > 7 based on targeted custom Ampliseq panel on the Ion Torrent PGM; or CCNE1 amplification on alternate CLIA platforms such as Foundation One, UW-OncoPlex – Cancer Gene Panel, Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT), Solid Tumor Genomic Assay (Life Technologies), etc. will also be eligible to be treated after principle investigator (PI) approval; patients with known CCNE1 amplification on local or commercial platforms can start treatment after planned biopsy or submission of recent archival sample; central next-generation sequencing (NGS) CCNE1 and fluorescence in situ hybridization (FISH) testing will be performed to confirm the result
Expression of PD-L1 in ?50% of tumor cells determined by the commercially available assay performed by the central laboratory
Stage IV or metastatic/recurrent non-small cell lung cancer; for expansion cohorts, patient’s tumor must also harbor a KRAS mutation detected in a CLIA certified laboratory
For phase I dose expansion cohorts the patient’s tumor must harbor a KRAS mutation detected by a CLIA certified laboratory
Patient has an AR-positive and PTEN-positive tumor as determined by using Clinical Laboratory Improvement Amendments (CLIA) compliant assays to identify AR-positive and PTEN-positive disease (AR positivity is defined as >= 1% of nuclear staining, PTEN positivity is defined as > 0% of nuclear staining).
Documented deleterious BRCA1/2 or PALB2 mutation (germline or somatic) as assessed by Clinical Laboratory Improvement Amendments (CLIA) certified laboratory; variants that are considered to be non-detrimental (“variants of uncertain significance”, “variants of unknown significance”, “variant, favor polymorphism” or “benign polymorphism” etc) are not sufficient for study entry
Required initial laboratory data (normal limits per treating institution; minor changes from the indicated laboratory guidelines will be allowed at the discretion of the treating team under special circumstances and reasons for the changes will be documented):
Carcinoma must be HPV-associated, which is defined as positive for p16 protein by immunohistochemistry (IHC); p16 positivity is defined as >= 70% of tumor cells demonstrating diffuse cytoplasmic and nuclear staining for p16 by immunohistochemistry in a Clinical Laboratory Improvement Amendments (CLIA) certified pathology lab. p16 testing is standard at participating institutions and may be conducted locally
Tumors must have undergone expanded molecular profiling with a Clinical Laboratory Improvement Act (CLIA)-certified platform that evaluates, at a minimum, RAS, PIK3CA, PTEN and BRAF mutations status
To be eligible for the study all participants (Cohort 1 and 2) are required to provide genomic profiling data from assays performed in a Clinical Laboratory Improvement Act (CLIA)-certified lab that demonstrate the following with respect to relevant biomarkers required for enrollment to the study as listed below; results from genomic profiling must be sent to the DFCI Coordinating Center prior to enrollment of the participant for central pathology review\r\n* Inactivation of CDKN2A/B or C in the tumor by homozygous deletion (evidence or more than single copy loss for any of the genes defined as array comparative genomic hybridization [CGH] log2 ratio of < 0.3 by array CGH; or from sequencing data with sufficient coverage for evaluation) AND\r\n* Validation of wild-type RB status (no deletion/losses more than single copy by copy number or sequencing data; and/or no inactivating mutations by sequencing)
The subject must have all of the following results as part of screening laboratory assessments (results from either the central laboratory or a local laboratory can be used for qualification):
Patients with previously identified IDH1/2 mutations from a Clinical Laboratory Improvement Act (CLIA) certified laboratory can be enrolled on the trial, but must be verified in the central study laboratory
Documented laboratory (lab) results confirming tumor mutational status must be obtained at screening; patients in whom mutational status cannot be determined will be deemed ineligible
Patients must have BRAFV600E or BRAFV600K mutations, identified by a Food and Drug Administration (FDA)-approved test at a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory (lab); if test at CLIA-certified lab used a non-FDA approved method, information about the assay must be provided
Formalin-fixed, paraffin-embedded tumor tissue must be submitted to Baylor College of Medicine (BCM) – Cancer Genetics Laboratory for Clinical Laboratory Improvement Amendments (CLIA)-certified KRAS mutation testing; results must be reported on the eligibility checklist during registration in order to receive treatment assignment\r\n* Note: if CLIA-certified KRAS mutation tumor testing is available from local or other source (e.g., Foundation Medicine) this report can be submitted to Statistical and Data Center (SDC) to meet this requirement
Melanoma must be documented to contain a BRAFV600 mutation by a Clinical Laboratory Improvement Amendment (CLIA) approved laboratory
Please contact study investigator and/or consult protocol document for specific details on laboratory criteria
Has a documented local diagnostic pathology of original biopsy confirmed by a Clinical Laboratory Improvement Amendments (CLIA)/College of American Pathologists (CAP) or equivalent laboratory certification
Has one of the following histologically confirmed tumors: (NOTE: Evidence of diagnostic pathology of original biopsy confirmed by a CLIA/CAP certified laboratory must be available)
Clinical/Laboratory Criteria:
Patients K-ras status must be wild type (not mutated); K-ras status determination may be based on either primary or metastatic tumor\r\n* NOTE: the assay must be performed by a Clinical Laboratory Improvement Amendments (CLIA) approved laboratory
DISEASE RELATED CRITERIA: Patients must have pathologically confirmed KRAS mutation (at codon 12, 13 and 61) positive non-small cell lung cancer (NSCLC) that is stage IV or recurrent; the specific subtype of KRAS mutation must be known; KRAS mutation testing must have been performed in a Clinical Laboratory Improvement Act (CLIA) certified laboratory; CLIA certified commercially available tests are acceptable
Presence of 17p del by central laboratory.
Presence of 11q del by central laboratory.
Acceptable organ function, as evidenced by the following laboratory data:
Has a documented local diagnostic pathology of original biopsy confirmed by a Clinical Laboratory Improvement Amendments (CLIA)/College of American Pathologists (CAP) or equivalent laboratory certification
Identification of a drug target/targets through molecular profiling performed as a part of routine clinical care and treatment recommendation by the Mayo Clinic Genomics Tumor Board (GTB); NOTE: If profile matches more than 1 treatment arm, final decision for treatment arm assignment to be made by patients treating physician; it will be required for the genomic aberration to be identified through a test in a Clinical Laboratory Improvement Amendments (CLIA) workflow; assays used will range from single gene abnormalities (e.g. fluorescent in situ hybridization [FISH] for human epidermal growth factor receptor 2 [ERBB2] amplifications) to next generation sequencing based gene panels (Foundation One®) to more comprehensive assays such as whole exome sequencing; the Mayo Clinic GTB will serve as the centralized point of data synthesis to allow for assessment of molecular profiling accomplished through a heterogeneous array of tests
SUB-PROTOCOL AIM A: Confirmation of advanced cancer with mTOR pathway aberrations as determined through routine clinical care using pathway aberrations performed in a CLIA certified laboratory; cancer genomic profiling tests incorporating next generation sequencing from archival formalin-fixed paraffin-embedded tissue (FFPE) are validated with sensitivities and specificities of 99% and 99%, respectively; in the assay, hybrid-capture–selected deoxyribonucleic acid (DNA) libraries are sequenced to depths targeting > 500 × coverage by non-polymerase chain reaction (PCR) duplicate read pairs, with > 99% of exons at coverage > 100 ×); multiplatform profiling may include immunohistochemistry and in situ hybridization methods with previously established negative/positive cutoffs performed in a CLIA certified lab; at least one pathway aberration must be identified; these must be confirmed in a CLIA certified lab; the potential mTOR aberrations that could be identified are listed below, please note that this list is not all inclusive; if a CLIA validated report lists an mTOR pathway inhibitor as a target drug for a genetic aberration, then it can be considered eligible for the purposes of this study; v-akt murine thymoma viral oncogene homolog 1 (AKT1), MTOR, phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA), tuberous sclerosis (TSC)1, TSC2, retrovirus-associated DNA sequence (Ras) homolog enriched in brain (RHEB), serine/threonine kinase 11 (STK11), neurofibromin (NF)1/2
The following laboratory results must be met within 21 days of patient registration:
Required baseline laboratory data as outlined in protocol
Laboratory criteria as:
Results must be available from a genomic test or immunohistochemistry (IHC) test for protein expression performed in a Clinical Laboratory Improvement Amendments (CLIA)-certified, College of American Pathologists (CAP) -accredited, New York State accredited (for labs offering services to residents of NY) laboratory that has registered the test with the National Institutes of Health (NIH) Genetic Test Registry or has established an integration with the TAPUR platform. The genomic or IHC test used to qualify a patient for participation in TAPUR may have been performed on any specimen of the patient's tumor obtained at any point during the patient's care at the discretion of the patient's treating physician. Genomic assays performed on cell-free DNA in plasma (\liquid biopsies\) will also be acceptable if the genomic analysis is performed in a laboratory that meets the criteria described above.
If HER2 negative by immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH), but activating somatic mutations of HER2 gene identified through genomic sequencing including but not limited to the following (Clinical Laboratory Improvement Act [CLIA] certified lab test): missense substitutions (G309A, G309E, S310F, S310Y, S653C, V659E, R678Q, V697L, T733I, L755S, L755P, E757A, D769H, D769Y, D769N, G776V, G776C, V777L, L841V, V842I, R849W, L869R, R896C); insertions/deletions (A775_G776insYVMA aka Y772_A755dup, G776VinsC, G776AinsVGC, G776 insertions, G778_S779insCPG, P780_781insGSP aka G778_P780dup, L755_T759del) and/or HER3 activating mutations; there is no limitation on the number of prior lines of systemic therapy or HER2-targeted therapies (prior neratinib not allowed)
Patients with active tumor lysis syndrome (TLS) either from laboratory or clinical changes
Recurrent respiratory papillomatosis (RRP) criteria\r\n* Histological diagnosis of RRP confirmed by pathology report from a Clinical Laboratory Improvement Act (CLIA)-certified laboratory\r\n* One of the following:\r\n** A Derkay anatomic score of 10 or greater and a history of two or more endoscopic interventions in the last 12 months for control of RRP\r\n** Pulmonary RRP with pulmonary disease that is measurable by computed tomography scan\r\n** Tracheal involvement with RRP that has required either two or more endoscopic interventions in the last 12 months or a tracheostomy
Patients must have either isocitrate dehydrogenase 1 (NADP+), soluble (IDH1) or isocitrate dehydrogenase 2 (NADP+), mitochondrial (IDH2) mutations (any known mutations) based on the SNaPshot platform or other molecular testing platform from either archived tissue or fresh biopsy (tested in Clinical Laboratory Improvement Amendments [CLIA]-certified lab)
All baseline laboratory requirements will be assessed and should be obtained within -14 days of study registration
Confirmation of advanced biliary cancer that is refractory or intolerant to gemcitabine or fluoropyrimidine based therapy with FGFR2 fusion [using next-gen sequencing assays (such as Foundation One) or fluorescent in situ hybridization (FISH) break-apart assays] or FGFR pathway mutation/amplification [using next-gen sequencing assays (such as Foundation One)]; assays must be performed in a Clinical Laboratory Improvement Amendments [CLIA] certified laboratory and done as a CLIA validated test or research use only [RUO] in a CLIA laboratory
Confirmation in a Clinical Laboratory Improvement Amendments (CLIA) certified laboratory or in an Food and Drug Administration (FDA)-approved assay that one of the patient’s thyroid tumors (primary tumor, recurrent tumor, or metastasis) possesses a BRAF mutation at V600
Patients must have histologically or cytologically confirmed adenocarcinoma of esophagus or gastroesophageal junction, or stomach which is Gli-1 positive (labeling index [LI] greater than or equal to 5%); testing is to be performed in a Clinical Laboratory Improvement Amendments (CLIA) certified laboratory; the patients must have an archival tumor sample to facilitate this testing
Agreed to participate in laboratory protocol PA13-0291 for the testing of biomarkers as described in this clinical protocol
All subjects must have EITHER the clinical diagnosis of NF1 using the National Institute of Health (NIH) consensus conference criteria, OR have a constitutional NF1 mutation documented in a Clinical Laboratory Improvement Amendments (CLIA)/College of American Pathologists (CAP) certified lab
Absence of Kit and PDGFRA mutation confirmed in a Clinical Laboratory Improvement Act (CLIA) certified laboratory
COHORT I: Patients must have MM that harbors an NF2 mutation believed to cause functional loss of the NF2 protein as determined by any Clinical Laboratory Improvement Act (CLIA) lab certified next generation sequencing (NGS) platform or NF2 loss must be documented by CLIA certified immunohistochemistry (IHC)
Carcinoma of the oropharynx associated with HPV as determined by p16 protein expression using immunohistochemistry (IHC) performed by a Clinical Laboratory Improvement Amendments (CLIA) approved laboratory; using p16 antibody obtained from Roche mtm laboratories AG (CINtec, clone E6H4) is recommended
Patients must be HLA-A201 as determined by a CLIA certified (or equivalent) clinical laboratory. (This determination will be made under a pre-enrollment screening ICF)
Laboratory requirements:
Cancers with positive BRAF V600 mutation detected by a Clinical Laboratory Improvement Act (CLIA)-certified laboratory
Patients with known K-RAS mutant (codon 12 or 13) detected by a Food and Drug Administration (FDA)-approved test in a CLIA-certified laboratory
Participants must have histologically or cytologically confirmed squamous cell carcinoma of the oropharynx, unknown primary, or nasopharynx that is p16 positive as determined by immunohistochemistry (IHC); tissue from the primary site must be available for biomarker studies and for polymerase chain reaction (PCR) testing; IHC must be performed in a lab verified by the central laboratory or the slides must be available for review by the central laboratory (Zhang, Mount Sinai School of Medicine [MSSM]) and PCR must be done in the central laboratory prior to randomization; HPV16 PCR must be performed and results available for randomization after induction
Any isolated laboratory abnormality suggestive of a serious autoimmune disease (e.g. hypothyroidism)
Must have met the following clinical laboratory criteria:
Laboratory test results within these ranges:
Any isolated laboratory abnormality suggestive of a serious autoimmune disease (e.g. hypothyroidism)
Test positive by FISH by the central laboratory designated by the Sponsor
Have FGFR2 gene fusion documented by a local or central laboratory using standard protocols and approved by local IRB/EC, by CLIA or other similar agency. If the FGFR2 gene fusion is identified by a laboratory other than the Sponsor's central laboratory, then archival and/or recent tissue biopsy samples or a tissue block suitable for genetic testing must be available for confirmatory testing by FISH by the Sponsor's central laboratory. If a subject has documentation from the central laboratory indicating that they test negative for FGFR2 gene fusion, that subject may not be enrolled in the study.
NTRK gene fusions will be identified via a CLIA certified (or equivalent) laboratory. Exception: Patients with Infantile Fibrosarcoma (IFS) and congenital mesoblastic nephroma (CMN) may be enrolled based on ETV6+ FISH test without identifying NTRK3
1p/19q deletion status assessment as determined by the Mayo Cytogenetics Laboratory has been received
All patients must have definitive evidence of t(8;21) or inv(16) by a Clinical Laboratory Improvement Amendments (CLIA) approved cytogenetics laboratory from initial diagnosis
Subject must meet all of the following criteria on the laboratory tests that will be analyzed centrally within 7 days prior to the first dose of study drug. In case of multiple laboratory data within this period, the most recent data should be used.
Positive for RAS mutation (neuroblastoma RAS viral [v-ras] oncogene homolog [NRAS] codon 12, 13, 61 mutation or Kirsten rat sarcoma viral oncogene homolog [KRAS] codon 12, 13, 61 mutation) at a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory prior to study entry; mutational testing will be performed on bone marrow sample and/or peripheral blood; patients with previously known RAS mutations prior to study entry may be considered positive for RAS mutation for eligibility prior to a CLIA-certified laboratory confirmation of such a mutation at the discretion of the investigator; (appropriate blood and/or bone marrow samples must be taken for RAS determination and submitted to a CLIA-certified laboratory prior to study entry); however, if such a mutation is not confirmed by the M D Anderson Cancer Center (MDACC)/other center’s CLIA-certified laboratory, the patient may be permitted to stay on the study if they wish and consent to do so but such patients’ data will be analyzed separately
Subject must meet all of the following criteria on the laboratory tests. In case of multiple laboratory data within this period, the most recent data should be used.
Acceptable laboratory results as indicated by protocol
Laboratory or clinical evidence of active infectious hepatitis
Subject with clinical or laboratory evidence of active DIC
Diagnosis of relapsed or refractory AML of any French American British (FAB) subtype except M3 and NPM1 genetic mutation detected by molecular assay; AML patients treated at Stanford have NPM1 molecular mutation status checked routinely at time of diagnosis in a Clinical Laboratory Improvement Amendment (CLIA)-certified laboratory
ERLOTINIB HYDROCHLORIDE ARM: Patients must have an EGFR tyrosine kinase inhibitor (TKI) sensitizing mutation as determined by analysis of the primary tumor or a metastatic site in a Clinical Laboratory Improvement Amendments (CLIA) certified laboratory
Patients tumors must have known PI3K pathway activation defined as EITHER of the following on a Clinical Laboratory Improvement Amendments (CLIA)-approved molecular diagnostics test:\r\n* Genomic alteration resulting in loss of phosphatase and tensin homolog (PTEN) function including a whole or partial gene deletion, frame shift mutations, or non-sense mutations; missense mutations in PTEN will not be considered qualifying\r\n* A previously characterized activating mutation in any component of the pathway including: phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA), v-akt murine thymoma viral oncogene homolog 1 (AKT1), phosphoinositide-3-kinase, regulatory subunit 1 (alpha) (PIK3R1), phosphoinositide-3-kinase, regulatory subunit 2 (beta) (PIK3R2), mTOR
Local testing for EGFR-mutations for this study is acceptable provided it was performed in a Clinical Laboratory Improvement Act (CLIA) certified lab
Patient must have acceptable, applicable laboratory requirements
CCND1 amplification and/or loss of p16 as determined by the central laboratory.
Tumors with at least one of the following known mutations in the PI-3K signaling pathway, via assays performed in a Clinical Laboratory Improvement Act (CLIA)-approved setting (Foundation Medicine FoundationOne test will be used; this assay uses a cut-off of 5% allele fraction for mutations; allele fraction will be requested on each sample):\r\n* PIK3CA,\r\n* PIK3CG, \r\n* PIK3R1, PIK3R5 and PIK3AP1 (regulatory subunits), \r\n* AKT and mTOR, or\r\n* PTEN \r\n** Note: PIK3CA amplification is not eligible
BRAF V600 mutation-positive tumor: as confirmed by a Clinical Laboratory Improvement Amendments (CLIA) approved local laboratory or equivalent.
Evidence of lack of HER2 oncogene amplification as determined by FISH testing by central laboratory
Uric acid, if elevated, must be corrected to within laboratory normal range prior to dosing
Additional Laboratory Requirements
Specific to the cohorts as designed to enroll patients with tumor protein p53 (TP53) mutations: TP53 mutations are identified by next-generation sequencing in a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory prior to screening
EXPANSION COHORT B ONLY: documented genetic alteration (mutation or homozygous deletion) in the PTEN gene, identified by the MSKCC Integrated Mutation Profiling of Actionable Cancer Targets (IMPACT) assay platform or other Clinical Laboratory Improvement Amendments (CLIA)-approved test
Liver toxicity criteria based on local laboratory results obtained within 24 hours of Baseline:
Subject must meet all of the following criteria on the laboratory tests that will be performed within 7 days prior to enrollment. In case of multiple laboratory data within this period, the most recent data should be used.
RAS wild-type status (by a Clinical Laboratory Improvement Amendments [CLIA] certified assay that includes all known mutations in Kirsten rat sarcoma viral oncogene homolog [KRAS], Harvey rat sarcoma viral oncogene homolog [HRAS], and neuroblastoma RAS viral [v-ras] oncogene homolog [NRAS])
Laboratory evaluation:
Documentation from the enrolling site confirming the presence of IDH mutation and 1p/19q status; the provided information must document assays performed in clinical laboratory improvement amendments (CLIA)-approved laboratories and be uploaded prior to Step 2 registration
GLIOMA PATIENTS: Standard of care next generation sequencing via a Clinical Laboratory Improvement Act (CLIA) certified platform must be available and at a minimum include IDH, RB, and ATRX status
For Part B, participants must have one of the following diagnoses histologically confirmed:\r\n* Neuroblastoma with evidence of mycn/myc positivity based on any of the following:\r\n** MYCN amplification (> 4 copy amplification) from Children's Oncology Group (COG) reference laboratory or other Clinical Laboratory Improvement Act (CLIA)-certified laboratory; or\r\n** Mycn protein expression >= 1+ according to validated assay in Children’s Hospital Los Angeles (CHLA) Clinical Pathology Laboratory; or\r\n** Myc expression >= 1+ according to validated assay in CHLA Clinical Pathology Laboratory\r\n* One of the following mature B cell lymphoma diagnoses:\r\n** Diffuse large B cell lymphoma\r\n** Burkitt lymphoma\r\n* An extra-cranial, solid tumor, other than neuroblastoma, with evidence of MYC or MYCN-alteration based on either of the following:\r\n** MYC or MYCN amplification from a CLIA-certified laboratory\r\n** MYC or MYCN high copy gain from a CLIA-certified laboratory
Documented ICOS positive expression using an analytically validated immunohistochemistry (IHC) assay by central laboratory for Part 1B and Part 2B biomarker cohorts only.
HIV-1 infection, as documented by a rapid HIV-1 test or any Food and Drug Administration (FDA)-approved HIV-1 enzyme or chemiluminescence immunoassay (E/CIA) test kit and confirmed by western blot at any time prior to study entry; alternatively, two HIV-1 RNA values > 200 copies/mL at least 24 hours apart performed by any laboratory that has Clinical Laboratory Improvement Amendments (CLIA) certification, or its equivalent may be used to document infection
Disease response must be confirmed with repeat laboratory studies at least 30 days apart
All clinical and laboratory studies for organ functions to determine eligibility must be performed within 7 days prior to enrollment unless otherwise indicated below.
Activating Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation (any G12, G13, Q61) confirmed by Clinical Laboratory Improvement Act (CLIA)-certified testing
Vitamin D level (25 hydroxy D2 + hydroxyl D3) confirmed by central laboratory review
Pre-imaging laboratory tests must be performed within 28 days prior to the [18F] FLT imaging procedure; these must be less than 4.0 times below or above the upper or lower limit range for the respective laboratory test for entry into the study (unless clinically not relevant); in those instances where a laboratory value is outside of this range, then such a patient will be ineligible for enrollment; for follow-up scanning sessions after therapy has been instituted, laboratory testing will also be required due to the use of [18F] FLT; the patients have brain tumors and will have received chemoradiation; therefore, many routine laboratory tests may not be within the typical normal range; as such, a factor of 4.0 times above or below the upper or lower value for the normal range for any laboratory test will also be used to determine the acceptable range for the 2nd and possibly 3rd imaging time points (unless clinically not relevant); the baseline laboratory testing will include liver enzymes (alanine transaminase [ALT], aspartate aminotransferase [AST]), bilirubin (total), serum electrolytes, complete blood count (CBC) with platelets, prothrombin time, partial thromboplastin time, blood urea nitrogen (BUN), and creatinine; for those patients receiving coumadin or another anticoagulant the upper limit for prothrombin time or partial thromboplastin time must not exceed 6 times the upper limit of the normal range
Patients who are diagnosed with NF1 using the National Institutes of Health (NIH) Consensus Conference criteria or have a confirmed NF1 mutation with analysis performed in a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory; NF1 mutation testing to confirm eligibility will not be performed on this protocol, but as part the POB separate screening study
Pre-treatment laboratory tests for patients receiving [18F]FLT must be performed within 21 days prior to study entry; these must be less than 4.0 times below or above the upper or lower limit range for the respective laboratory test for entry into the study (unless clinically not relevant); in those instances where a baseline laboratory value is outside of this range, then such a patient will be ineligible for enrollment; for the follow-up scanning sessions after therapy has been instituted, laboratory testing will also be required due to the use of FLT; the patients have brain tumors and will have received various forms of therapy; therefore, many routine laboratory tests may not be within the typical normal range; as such, a factor of 4.0 times above or below the upper or lower value for the normal range for any laboratory test will also be used to determine the acceptable range for the 2nd and possible 3rd imaging time points (unless clinically not relevant); the baseline laboratory testing will include liver enzymes (alanine aminotransferase [ALT], aspartate aminotransferase [AST], alkaline phosphatase [ALK], lactate dehydrogenase [LDH]), bilirubin (total), serum electrolytes, complete blood count (CBC) with platelets and, prothrombin time, partial thromboplastin time, blood urea nitrogen (BUN), creatinine; previous urinalysis abnormalities will not preclude the patient from being studied; for those patients receiving Coumadin or another anticoagulant the upper limit for prothrombin time or partial thromboplastin time must not exceed 6 times the upper limit of the normal range
Abnormalities in hematological, clinical chemical or any other laboratory variables at Screening measured by the central or local laboratory regarded as clinically relevant by the investigator unless they are due to underlying disease or condition.
Peripheral blood MDSC level ? 10% of mononuclear cell fraction (assayed at a central laboratory)