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Report for Clinical Trial NCT01877811

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

An Open-Label, Phase 1/1b, Single-Agent Study of RXDX-105 in Patients With Advanced Solid Tumors

This is a first-in-human, multicenter, open-label study consisting of 2 phases. Phase 1 is a dose escalation study of RXDX-105 (formerly known as CEP-32496) in patients with advanced solid tumors aimed at defining the recommended Phase 2 dose (RP2D) and schedule for administration. Phase 1b is a dose expansion in approximately 90 patients with advanced solid tumors with specific histologies and/or molecular alterations of interest. Patients in Phase 1b will be treated at the RP2D determined in Phase 1.

NCT01877811 Solid Tumors
MeSH: Neoplasms
HPO: Neoplasm

1 Interventions

Name: RXDX-105

Description: During Phase 1/1b, subjects will receive daily oral doses of RXDX-105 in 28-day cycles (except for Day 2 of Cycle 1). To determine the recommended Phase 2 dose (RP2D), doses will be administered in an escalated fashion starting at 20 mg/day. During Phase 1b, subjects will be administered the RP2D in 28-day treatment cycles until documented radiographic progression, unacceptable toxicity, withdrawal of consent, or protocol specified parameters to stop treatment.

Type: Drug

RXDX-105


Primary Outcomes

Description: From signing of the informed consent up to approximately 12 months

Measure: Phase 1: Dose Limiting Toxicities

Time: Approximately 12 months

Description: From signing of the informed consent up to approximately 12 months

Measure: Phase 1: Occurrence of Adverse Events

Time: Approximately 12 months

Description: To further assess the safety profile and tolerability of RXDX-105 at the RP2D

Measure: Phase 1b: Occurrence of Adverse Events

Time: Approximately 12 months

Secondary Outcomes

Measure: Phase 1: Maximum observed plasma drug concentration (Cmax)

Time: Day 1 to Day 16

Measure: Phase 1: Time of maximum observed plasma drug concentration (tmax)

Time: Day 1 to Day 16

Measure: Phase 1: Area under the plasma drug concentration versus time curve from time 0 to infinity (AUC0-∞)

Time: Day 1 to Day 16

Measure: Phase 1: Area under the plasma drug concentration versus time curve from time 0 to the last measureable drug concentration (AUC0-t)

Time: Day 1 to Day 16

Measure: Phase 1: Area under the plasma drug concentration versus time curve from time 0 to 24 hours after study drug administration (AUC0-24)

Time: Day 1 to Day 16

Measure: Phase 1: Terminal elimination rate constant (λz)

Time: Day 1 to Day 16

Measure: Phase 1: Terminal elimination half-life (t1/2)

Time: Day 1 to Day 16

Measure: Phase 1: Apparent clearance of study drug from plasma (CL/F)

Time: Day 1 to Day 16

Description: Objective response rate is defined as the proportion of patients with advanced solid tumors achieving best overall response of complete response (CR), or partial response (PR), as assessed using RECIST v1.1

Measure: Phase 1b: Objective Response Rate

Time: Approximately 12 months

Description: The duration of objective response is defined as the time interval from the date of first documented response (CR or PR) to disease progression or death, whichever occurs first

Measure: Phase 1b: Duration of Objective Response

Time: Approximately 12 months

Description: Clinical benefit rate is defined as the proportion of patients achieving a complete response (CR), partial response (PR) or stable disease (SD) for 6 months

Measure: Phase 1b: Clinical Benefit Rate

Time: Approximately 12 months

Purpose: Treatment

Single Group Assignment


There is one SNP

SNPs


1 V600E

Inclusion Criteria for Phase 1b: 1. Patients must have histologically or cytologically confirmed advanced solid tumors with a histology and/or molecular alteration of interest as defined in Section 4, detected by a CLIA-certified or equivalently accredited diagnostic laboratory • Squamous NSCLC and Non-squamous NSCLC (no known RET alterations or BRAF V600E mutations) patients must have archival tissue available for analysis by Ignyta; all other patients must send tissue to Ignyta, if tissue is available 2. Prior Treatment: - Patients with BRAF V600E mutations must be TKI-naïve; any number of other prior therapies are allowed - NSCLC patients with RET alterations who have had a prior RET inhibitor or are RET inhibitor-naïve will be enrolled; (any number of other prior therapies are allowed); all other histologies with RET alterations must be RET inhibitor-naïve - Patients with Squamous NSCLC and Non-squamous NSCLC (no known RET alterations or BRAF V600E mutations) may have had prior TKIs and any number of other prior therapies 3. Measurable disease according to RECIST v1.1 for all patients except patients with RET altered tumors; patients with RET altered tumors must have evaluable disease, but are not required to have measurable disease 4. Patients with treated, stable CNS metastases, including leptomeningeal carcinomatosis are allowed. --- V600E ---

Inclusion Criteria for Phase 1b: 1. Patients must have histologically or cytologically confirmed advanced solid tumors with a histology and/or molecular alteration of interest as defined in Section 4, detected by a CLIA-certified or equivalently accredited diagnostic laboratory • Squamous NSCLC and Non-squamous NSCLC (no known RET alterations or BRAF V600E mutations) patients must have archival tissue available for analysis by Ignyta; all other patients must send tissue to Ignyta, if tissue is available 2. Prior Treatment: - Patients with BRAF V600E mutations must be TKI-naïve; any number of other prior therapies are allowed - NSCLC patients with RET alterations who have had a prior RET inhibitor or are RET inhibitor-naïve will be enrolled; (any number of other prior therapies are allowed); all other histologies with RET alterations must be RET inhibitor-naïve - Patients with Squamous NSCLC and Non-squamous NSCLC (no known RET alterations or BRAF V600E mutations) may have had prior TKIs and any number of other prior therapies 3. Measurable disease according to RECIST v1.1 for all patients except patients with RET altered tumors; patients with RET altered tumors must have evaluable disease, but are not required to have measurable disease 4. Patients with treated, stable CNS metastases, including leptomeningeal carcinomatosis are allowed. --- V600E --- --- V600E ---

Inclusion Criteria for Phase 1b: 1. Patients must have histologically or cytologically confirmed advanced solid tumors with a histology and/or molecular alteration of interest as defined in Section 4, detected by a CLIA-certified or equivalently accredited diagnostic laboratory • Squamous NSCLC and Non-squamous NSCLC (no known RET alterations or BRAF V600E mutations) patients must have archival tissue available for analysis by Ignyta; all other patients must send tissue to Ignyta, if tissue is available 2. Prior Treatment: - Patients with BRAF V600E mutations must be TKI-naïve; any number of other prior therapies are allowed - NSCLC patients with RET alterations who have had a prior RET inhibitor or are RET inhibitor-naïve will be enrolled; (any number of other prior therapies are allowed); all other histologies with RET alterations must be RET inhibitor-naïve - Patients with Squamous NSCLC and Non-squamous NSCLC (no known RET alterations or BRAF V600E mutations) may have had prior TKIs and any number of other prior therapies 3. Measurable disease according to RECIST v1.1 for all patients except patients with RET altered tumors; patients with RET altered tumors must have evaluable disease, but are not required to have measurable disease 4. Patients with treated, stable CNS metastases, including leptomeningeal carcinomatosis are allowed. --- V600E --- --- V600E --- --- V600E ---

Known hypersensitivity to any of the components of RXDX-105 Inclusion Criteria for Phase 1b: 1. Patients must have histologically or cytologically confirmed advanced solid tumors with a histology and/or molecular alteration of interest as defined in Section 4, detected by a CLIA-certified or equivalently accredited diagnostic laboratory • Squamous NSCLC and Non-squamous NSCLC (no known RET alterations or BRAF V600E mutations) patients must have archival tissue available for analysis by Ignyta; all other patients must send tissue to Ignyta, if tissue is available 2. Prior Treatment: - Patients with BRAF V600E mutations must be TKI-naïve; any number of other prior therapies are allowed - NSCLC patients with RET alterations who have had a prior RET inhibitor or are RET inhibitor-naïve will be enrolled; (any number of other prior therapies are allowed); all other histologies with RET alterations must be RET inhibitor-naïve - Patients with Squamous NSCLC and Non-squamous NSCLC (no known RET alterations or BRAF V600E mutations) may have had prior TKIs and any number of other prior therapies 3. Measurable disease according to RECIST v1.1 for all patients except patients with RET altered tumors; patients with RET altered tumors must have evaluable disease, but are not required to have measurable disease 4. Patients with treated, stable CNS metastases, including leptomeningeal carcinomatosis are allowed. --- V600E ---

Known hypersensitivity to any of the components of RXDX-105 Inclusion Criteria for Phase 1b: 1. Patients must have histologically or cytologically confirmed advanced solid tumors with a histology and/or molecular alteration of interest as defined in Section 4, detected by a CLIA-certified or equivalently accredited diagnostic laboratory • Squamous NSCLC and Non-squamous NSCLC (no known RET alterations or BRAF V600E mutations) patients must have archival tissue available for analysis by Ignyta; all other patients must send tissue to Ignyta, if tissue is available 2. Prior Treatment: - Patients with BRAF V600E mutations must be TKI-naïve; any number of other prior therapies are allowed - NSCLC patients with RET alterations who have had a prior RET inhibitor or are RET inhibitor-naïve will be enrolled; (any number of other prior therapies are allowed); all other histologies with RET alterations must be RET inhibitor-naïve - Patients with Squamous NSCLC and Non-squamous NSCLC (no known RET alterations or BRAF V600E mutations) may have had prior TKIs and any number of other prior therapies 3. Measurable disease according to RECIST v1.1 for all patients except patients with RET altered tumors; patients with RET altered tumors must have evaluable disease, but are not required to have measurable disease 4. Patients with treated, stable CNS metastases, including leptomeningeal carcinomatosis are allowed. --- V600E --- --- V600E ---

Known hypersensitivity to any of the components of RXDX-105 Inclusion Criteria for Phase 1b: 1. Patients must have histologically or cytologically confirmed advanced solid tumors with a histology and/or molecular alteration of interest as defined in Section 4, detected by a CLIA-certified or equivalently accredited diagnostic laboratory • Squamous NSCLC and Non-squamous NSCLC (no known RET alterations or BRAF V600E mutations) patients must have archival tissue available for analysis by Ignyta; all other patients must send tissue to Ignyta, if tissue is available 2. Prior Treatment: - Patients with BRAF V600E mutations must be TKI-naïve; any number of other prior therapies are allowed - NSCLC patients with RET alterations who have had a prior RET inhibitor or are RET inhibitor-naïve will be enrolled; (any number of other prior therapies are allowed); all other histologies with RET alterations must be RET inhibitor-naïve - Patients with Squamous NSCLC and Non-squamous NSCLC (no known RET alterations or BRAF V600E mutations) may have had prior TKIs and any number of other prior therapies 3. Measurable disease according to RECIST v1.1 for all patients except patients with RET altered tumors; patients with RET altered tumors must have evaluable disease, but are not required to have measurable disease 4. Patients with treated, stable CNS metastases, including leptomeningeal carcinomatosis are allowed. --- V600E --- --- V600E --- --- V600E ---



HPO Nodes


HPO:
Neoplasm
Genes 1473
GPC3 LETM1 LZTS1 REST MPL ARID1B RPL18 MGMT GLI3 BIRC3 ZSWIM6 TRNS2 ETV6 HNF1B KIT BRCA1 SUFU PLAG1 SOX9 TP63 CTSC RASA1 ATRX TRIM37 SUFU BTK CYP11B1 NOTCH3 EPCAM PORCN PIGL AR TET2 FH TGIF1 HMBS ATRX TREX1 SMAD4 KRT17 FGFR1 WDPCP SF3B1 GPR101 KIT GLI1 SLC25A11 XRCC4 SDHD PRKCD RNF43 SDHB BAP1 EGFR PIGA NF1 ASCL1 MPL RET C2CD3 GDNF NR5A1 DICER1 TNFRSF4 CASP10 TERC FGF8 PSAP CIB1 SLC22A18 PTCH2 ENPP1 CDKN2C SLC25A11 GPR101 KIT AXIN2 TREX1 DYNC2LI1 ERCC4 RPS14 COMP TINF2 FOXE1 DHCR24 RPS7 TYROBP HOXD13 ERBB2 BLK EYA1 ZFPM2 ERCC6 NLRP1 STAC3 ERCC5 NUTM1 MEN1 WT1 BCL10 GNPTAB KRAS TP53 KDR PUF60 TRNF FCN3 SDHC KCNH1 MSTO1 EP300 BUB1B GNA11 KCNE3 DOCK8 SEMA3C ACD GLI2 SMPD1 SUFU NF1 PTCH2 ACAN DCC WT1 CTSA KIF11 BCR SRGAP1 KIT PTEN LEMD3 MLLT10 SCN4A BRCA2 BMPR1A NOTCH3 SEC23A CDKN1C BARD1 SPIB RSPO1 MC2R CALR ATP6V1B2 NBN RAD54L MST1 SUFU MYCN TMEM127 SRD5A3 IGF2 CD28 RUNX1 OGG1 HAX1 SDHC CTNNB1 MST1R SDHA IGF2 KCNJ10 IL12RB1 MEN1 RAD51 TFE3 ND5 MMEL1 MVK APC FLI1 RNF6 NF1 BRCA2 SUFU GPC6 NR4A3 TTC37 KIT NRTN BLNK IGH SPRED1 TXNRD2 IGF2R FOXP1 BUB1B SOS1 LRP5 GJB2 DNMT3A PMS2 PRKN RET MSH6 ACVRL1 MPLKIP ERCC2 AIP GNAS TAL1 NNT RECQL4 PMS1 DLL1 EIF2AK4 STAT6 MNX1 SDHB KRAS MEN1 MN1 SH2B3 EFL1 VHL KLLN RMRP RUNX1 SIX3 GDNF FANCD2 EXT1 CDH23 BRD4 DLEC1 NODAL CARMIL2 SDHB MSH2 HMBS SMAD4 SRP72 NRAS DOCK8 SPRTN BRCA1 MAP2K1 KRT14 LETM1 TERT MAP2K2 HRAS WHCR WT1 IDH1 TMEM107 SCN10A GJB3 SDHD KRAS GATA1 RPS20 GJB2 SLX4 USP8 PRKAR1A CR2 JAK2 HFE MPL POT1 BRCA2 GNAI3 SDHB ALK OCA2 TP53 GPC4 ACTG2 CTNNB1 HSPG2 AR FGFR1 STK4 MET TMC8 MRAP MSH6 CCBE1 EWSR1 LMO1 EDN3 LEMD3 PGM3 FGFR3 CASP8 RB1CC1 SCN9A FANCL TG SDHD COX3 IGF2 COL11A2 AGGF1 GPR101 PRKN PLCB4 SDHD NF1 GTF2E2 MAP2K1 ESCO2 CDC73 WRAP53 TET2 PDGFRB RNASEH2A RAD21 HNF1A TGFBR2 POLD1 COX2 TNFRSF10B MINPP1 DNAJC21 FAS EXT1 SLC26A2 APC SDHAF2 TINF2 LIG4 POLR1D WWOX TMC6 RPS19 ERCC2 SASH1 MC1R MVD SEC23B CYP2A6 GPC3 KIT HRAS RAD54L SDHA GDNF NKX2-1 GFI1 ALX3 STAT3 MYH11 DYNC2LI1 FGFR2 TCOF1 PTEN MAFA PIK3R1 SLC25A13 HRAS VHL COL7A1 GNAS FGFR2 PIK3CA GPC4 DICER1 ERCC3 PIK3CA RAD51C RB1 RMRP MLH3 ATM COL7A1 LIG4 NF1 VAMP7 RPL35A RB1 SETD2 BCL10 LPP NRAS KRAS ABCA5 ERCC2 PDE6D KCNQ1OT1 MS4A1 SLC22A18 APC LIG4 JAK2 FANCD2 GAS1 STAG3 NRAS PALLD SLC22A18 RFWD3 PPP2R1B APC PTPN11 PTEN WIPF1 PIK3CA NOP10 IL7 UROD TNFRSF1B TP53 REST SLC37A4 NHP2 CXCR4 KIT CYSLTR2 FZD2 ALX4 BMPR1A SRY TRNQ SDHD PIGL CCM2 FIBP FANCI GJB4 SPINK1 RPL10 NSD2 MAP3K1 RET CDK4 HSPA9 TET2 GFI1B MAD2L2 DCC AP2S1 SMAD7 BRCA2 TRNK ERCC3 BRCA1 ELANE SFTPC PTH1R COL1A1 FUZ OFD1 RET FLT4 PRKAR1A SBDS RPL26 SMARCE1 SMARCAD1 MSH2 BCR GPR35 INTU FANCA STAT1 ANTXR2 FGFRL1 TUBB BRAF SLX4 CASP10 TERT RAD21 MTOR TRIP13 MYD88 DPM1 RSPO1 PTPN11 CTNNB1 AIP PTEN VANGL1 CYP2D6 RPS10 GCK KRT16 DNAJC21 BCL2 AKT1 KRAS KLF6 NOTCH1 FLNA MAX NF2 PALB2 TP53 PSENEN RNF6 TSC1 HNF1B TP53 RFWD3 SDHD PERP TP53 DIS3L2 B3GALT6 STS PDGFB SMARCB1 BRAF BRIP1 CBFB BUB1 BLM INHBA CALR NBN MLH3 TAF1 MLF1 PIK3CA MSH2 CTLA4 ND6 PALB2 WT1 PTCH1 POLE ADA MC1R FLT4 ATP7A MLH3 SMO TRNF NRAS LMNA DLST TRNL1 MTAP TP53 ZAP70 SDHB CHEK2 PALB2 FLT4 CDK4 NBN MSR1 CC2D2A TNPO3 ECE1 RPS15A NAGS TMEM67 HNF1A PIK3CA ATP7A AKT1 NRAS SDHAF2 CXCR4 TSC2 NF2 EPHB2 WDPCP OFD1 BUB1 FLT3 APC SMARCA4 CDKN2A RPS29 MCM4 PDGFRA ESCO2 CTC1 ESR1 SDHB MSH6 APC HABP2 GNAQ KIF1B SH3GL1 CD70 MPL IGH ZIC2 GCM2 VEGFC HRAS CTNNB1 KCNH1 LRRC8A BRAF FAS ICOS NSD1 RNF43 AKT1 BIN1 DLC1 SH2B3 RARA WNT10A CARD14 SDHC EXOC6B ESCO2 POLR1C G6PC MSH6 KRT1 PDX1 TNFRSF13C ERCC3 EVC SNAI2 CD79A BRCA1 RNASEH2B CCND1 TP53 RPS19 H19 H19 BRCA2 TFAP2A ARMC5 FASLG FGFR3 APC F5 EDN1 MAP3K8 AIP APC AKT1 TERC CCND1 CEL MYC TP53 GPC4 ERCC5 HNF1A POLE DAXX NUP214 TRIP13 AKT1 TET2 CDC73 ND1 MUTYH PIK3R1 TERT CEBPA EXT2 OCRL DIS3L2 ADAR TGFBR2 BRCA2 MRE11 SOS1 HNF4A FAH TMEM127 WT1 AXIN2 TCF4 EDN3 PTPN3 KRAS SEMA4A PIK3CA XPA MFN2 TINF2 PIK3CA APPL1 RUNX1 GNPTAB FGFR3 NRAS PDCD10 RAG2 PTEN CTNNB1 SOX2 BMPR1A HBB TERT USP9X NFKB1 FANCC PRF1 WRN SRY SRSF2 PMS2 RHBDF2 PHOX2B RPS17 PAX3 RECQL4 KIF1B SQSTM1 RB1 EXT1 XPC CYLD TOP2A MYD88 CDKN1B TET2 GJB2 PTEN UBE2T RTEL1 PTCH1 KLHDC8B GATA1 POLH JAK2 RHOH FLCN DCLRE1C MTMR14 GTF2H5 PTEN SBDS TBC1D24 PAX7 AR TP53 ASPSCR1 MTM1 RECQL4 ERCC2 TGFBR2 ERCC4 JAK2 SF3B1 CDKN2B XPC GATA4 KIT POU2AF1 BRCA2 GREM1 CDON NTHL1 DICER1 GINS1 ATM RAD51D SHOX EXT1 RASGRP1 WT1 GATA2 NF2 ERCC4 TUBB MBTPS2 DHCR7 MYLK KCNN3 TCTN3 TMEM216 TMEM231 KRT1 CTNNB1 MPL PDGFRB FANCG RPGRIP1L KEAP1 DICER1 WT1 BAP1 FOXI1 ERCC4 CDKN2A FGFR3 KDSR CBL HRAS BMPR1A DISP1 RELA MAP3K1 PARN BCR ENG COL7A1 LMOD1 KRAS PAX6 SNAI2 GLI3 FANCF FOXO1 RPL15 TBX18 TRPV3 PIK3CA NRAS CDH1 GNAS SMARCB1 KLF11 ADA2 EDN3 POU6F2 CDH1 GNAS IL1B SMAD4 H19-ICR SDHB STK11 NF2 TRIM28 SEC23A SLCO2A1 BRCA2 BRAF DNMT3A MDM2 BMP2 BRCA2 DHH NRAS POU6F2 CTBP1 PTCH2 FLCN CALR BAP1 LIG4 HRAS REST BRAF SAMD9 NDP TYR KRT17 MUC5B PRSS1 MEN1 NPM1 ITK MSH2 CYLD TAL2 SRP54 IFIH1 HMMR TCTN3 ND5 JAK2 FAM20C RET NEK9 DMRT3 KRAS MINPP1 SH3KBP1 THPO FAH KRT5 JAK2 PHKG2 TSC1 TNFRSF13C MEN1 FH RPL31 FANCG PIK3CA IL2RG DNAJC21 VANGL2 MYO1H ALX1 CDKN2A AIP H19 NRAS TWIST1 PTEN TRNK TRPS1 RPS26 MAPRE2 RPS27 TCF3 KRT17 ERCC6 DHH MMP1 FGFR1 SEMA3D PTCH1 ABL1 CDKN2A SKI APC WWOX ZSWIM6 NF2 WNT10A KRAS GPC3 REST GJB6 HRAS VHL CTNNB1 TGFBR1 IL6 TDGF1 RPL11 IL1RN BRCA1 MGAT2 POT1 ASCC1 XPA TBX2 FLCN HFE NTHL1 SMARCB1 DVL3 TRNH IDH1 FANCA LAMB3 CD79B RAD51C PRDM16 PHOX2B GNAQ CCL2 PDGFRA CREB1 SRP54 PIEZO2 TRNL1 GBA GNAS WNT5A PIK3CA STS FANCB KRAS MAGT1 RAD51 IDH1 TNFRSF13B TREM2 GABRD BCL10 SKIV2L POLD1 KRIT1 KRAS ARSA SMAD4 RAD51 TP53 DIS3L2 KIAA0753 PRLR CD96 LZTR1 WRN GATA2 EDNRB MUTYH ATM CHIC2 TP53 CYLD PAX4 SLC26A4 RTEL1 VHL NEK1 TRNS1 GCM2 TYR ATP7B CTHRC1 BRAF ASXL1 OFD1 MLH1 CDKN1A PHOX2B XRCC2 CD19 RB1 FOXC2 TRIM28 EWSR1 TERT GNA11 F13B CDKN2A KARS1 BCL10 TP53 WT1 CDKN2A FDPS KIT COX1 COL14A1 VHL WT1 TERT SMAD4 STAR NUMA1 RPL5 PDGFB PCGF2 CFTR KCNQ1OT1 KIT GJA1 GNAQ CD27 FANCC IDH2 EVC2 BRCA2 TCF4 KRAS PIK3CA CDC73 ACVR1 BRIP1 TRNW PRCC GCGR CDKN1B STK11 SCN11A TGFBR2 AXIN2 ERBB2 RPL35 APC TSC2 IL12A SSX2 TET2 KIF1B DICER1 TRNP BTK CCDC22 PDGFRA ALX3 ADAMTS3 CD81 RET DKC1 GLI3 FGF3 SMAD4 STK11 ERCC6 WT1 ELANE C11ORF95 SAMD9L SLC45A2 NQO2 PTPN11 ATR PDGFRL TNFSF12 BRCA2 ADA BUB1B FASLG GDF5 KRAS CPLANE1 CREBBP CDC73 CLCNKB GATA2 CTRC SDHA ACTB APC BMPER SPINK1 APC2 MC1R FOXI1 DYNC2H1 KIT PPM1D SDHC NSD1 SDHC DDX41 ANTXR1 CASP8 F13A1 SUFU INS NUP214 ANTXR2 KIF7 NFKB2 ABCC8 TARS1 ERCC3 TCIRG1 ND4 ERCC2 GNAS TERT WASHC5 SLC49A4 RERE CALR MSH3 PHOX2B SLC25A13 BMPR1B CYLD SIX6 ASCL1 IDH2 FAN1 CHRNG CBL NEUROD1 MSH3 THPO VANGL1 CDKN2B TAF15 PTCH2 HMGA2 MSH6 CHEK2 FN1 GATA2 IRF1 KRAS BMPR1A NPM1 ERCC3 CDH1 ALK DNM2 ERBB3 PTPN11 DLST MUTYH PARN GFI1 NBN FGFR3 CHEK2 EP300 RNF113A TNFSF15 TEK TERF2IP ICOS COL18A1 TNFSF12 BRAF CHEK2 IFNG TMC6 USB1 KDM6B GJC2 SLC26A2 MDH2 TP53 ENG MLH1 KRT6B MNX1 PDGFB TRNH POLE CASP10 HPGD TET2 RB1 PHOX2B JAG1 GNB1 ACD TNFRSF13B MYC BRAF TSC1 SAMD9L BCL10 H19 POT1 USP8 IGF2 OFD1 CYP11B2 KCNQ1 CDH1 LMX1B TET2 ANTXR1 JAK2 SMARCB1 ELMO2 PTCH1 SIX1 L2HGDH WRAP53 BUB3 AXIN1 RET KCNJ11 ABL1 FANCE RAD54B FANCM TSC2 MAX IGHM TSC1 HACE1 CASR RNF139 MITF RAF1 WT1 TCTN3 POLH LIG4 TP53 KRT10 AAGAB SRY RAD50 TNFRSF1B TRNQ DNASE1L3 FAM149B1 KRT9 VHL FLCN TBXT SLC37A4 DKC1 PNP DDB2 SETBP1 ECM1 MSH2 CR2 COL2A1 COL7A1 MLH1 FH SFTPA2 PIK3CA FOXH1 MET HNF4A H19 KAT6B GPR143 PHB PMS1 ATP7A FAT4 TJP2 TFAP2A GDF2 AHCY TSC2 CD19 TRNS1 BDNF TRIP13 AKT1 FGFR2 RAG1 BRCA1 SDHC MLH1 XRCC3 NSD2 LMNA SDHC TERC EXT2 PIK3CA MSH3 SDHD SRC CHEK2 C1S ABCA5 HBB RYR1 FGFR2 CDC73 KIT FANCE RET LYST KCNJ10 BCHE HDAC4 INPP5E CRKL PHOX2B BAP1 CPLX1 PDGFRB ARL6IP6 RNASEL SETBP1 CTLA4 PALB2 DCLRE1C NSUN2 XIAP TRNS2 BMPR1A IL7R BCL6 COL4A5 PIK3CA NOD2 PRKAR1A NELFA IL2RG MYH8 RHBDF2 IGLL1 PIK3CA SERPINA1 FOXE1 ARHGAP26 TCF4 MITF ABCB11 ERBB2 GNA14 SLC26A2 NSD1 SH2B3 STK11 PTCH1 GDNF RPL27 DHCR7 WAS CIB1 SHH CACNA1S LIN28B SF3B1 ATM PRKCD RPS24 LAMA3 ATRX CASP8 AKT1 OPCML HFE SH2D1A ING1 CCND1 SLC12A3 HABP2 H19 LAMC2 RAD51C NAB2 NRAS MAPK1 CPLANE1 CYP26C1 CDKN1B CHD7 IGH MYF6 BLM ASXL1 FH NEK1 HLA-DRB1 SLC26A4 RPS14 SHOX RNASEH2C SMARCD2 GATA2 CDH23 WT1 EPCAM NR0B1 KLLN DVL1 SEC23B GPC3 SLC17A9 BRCA1 SRP54 DKC1 RECQL4 CD28 PTPN11 HRAS NBEAL2 BARD1 MLH1 DDB2 PMS2 IRF1 ABCC6 EXT2 ASXL1 TSR2 PTEN MALT1 PTEN BCR PALB2 BRIP1 SSX1 PHKA2 FGFR2 SDHB FERMT1 KCNAB2 FLT3 PMVK MSTO1 CEP57 MMP1 PICALM IRF5 TP53 PTPRJ RNR1 WWOX PLCD1 RPS28 FGFR3 COL2A1 IKBKG TERT RASA1 SAMHD1 PHF21A