SNPMiner Trials by Shray Alag

L858R (332) T790M (322) V600E (266) T315I (107) L861Q (92) M184V (68) V617F (58) K65R (53) G20210A (53) V600K (52) C282Y (50) V66M (49) G551D (42) P13K (39) C677T (35) A118G (29) I84V (27) V158M (26) H63D (25) V32I (24) S768I (24) I50V (23) I47V (21) K103N (21) K27M (20) Y181C (20) L33F (19) T380A (18) L76V (18) G12C (18) D842V (18) R117H (17) D816V (17) S1251N (17) S1255P (17) G178R (17) G1244E (17) S549R (17) G1349D (17) V82A (16) M41L (16) S549N (16) C3435T (16) G551S (16) Q151M (16) Q12H (15) K219Q (15) I54L (15) K70E (14) C797S (14) G719A (13) L90M (13) L74V (13) E138A (13) D67N (13) K70R (13) L89V (13) L210W (13) Y188L (13) G11778A (12) P4503A (12) L265P (12) M46I (12) I54M (12) G12D (12) E255K (12) V11I (12) R132H (12) G48V (11) V299L (11) D961H (11) T74P (11) R192G (11) T25W (10) K101E (10) G2677T (9) V106A (9) G12V (9) M184I (9) H221Y (9) V30M (9) Y253H (9) V600D (9) G1691A (8) F317L (8) F227C (8) T215Y (8) I50L (8) A1298C (8) L100I (8) I148M (7) N155H (7) F359C (7) S298P (7) G190A (7) M230I (7) C1236T (7) V600R (7) Y188C (7) G2019S (7) Q12W (6) P225H (6) Y93H (6) V108I (6) A3243G (6) G93A (6) G73S (6) P12A (6) Y115F (6) E545K (6) Q148H (6) Y537S (6) E542K (6) I10A (6) M230L (6) H1047R (6) N40D (6) D299G (6) N236T (6) D30N (6) M235T (6) T315A (6) D538G (6) T87Q (5) I47A (5) L74I (5) E92Q (5) N680S (5) A455E (5) M204V (5) D1152H (5) L755S (5) G13D (5) G190S (5) N363S (5) A181V (5) V179L (5) L24I (5) N88S (5) A2143G (5) T399I (5) M36I (5) F53L (5) R263K (5) R132C (5) V777L (5) T1405N (4) D579G (4) G719C (4) N370S (4) R117C (4) Q16W (4) L98H (4) A98G (4) K20M (4) E138G (4) E138K (4) L31M (4) E157Q (4) L10F (4) Q80K (4) C31G (4) G1202R (4) Q252H (4) L206W (4) P140K (4) C19P (4) I54V (4) K76T (4) Y537C (4) I1314L (4) S945L (4) Y402H (4) P1446A (4) V179D (4) N88D (4) A6986G (4) A1166C (4) G970R (4) Y181I (4) R352Q (4) G2385R (4) S310F (4) P67L (4) R1070W (4) G140A (4) E23K (4) S463P (4) T14484C (3) G719S (3) R206H (3) S1400A (3) S1400I (3) A71V (3) C134W (3) R24W (3) C481S (3) T24H (3) V122I (3) T47D (3) A636P (3) S977F (3) G118R (3) G3460A (3) N312S (3) D988Y (3) L444P (3) V659E (3) V769L (3) A147T (3) E10A (3) Q24W (3) L861R (3) R678Q (3) Q27E (3) E17K (3) Q148R (3) A1555G (3) S49G (3) Y537N (3) R16G (3) I10E (3) V158F (3) G21210A (3) K55R (3) V205C (3) Y181V (3) A2142G (3) R506Q (3) E298D (3) L211A (3) R172K (3) V843I (3) Y143R (3) R572Y (3) G143E (3) G1321A (3) V842I (3) H295R (3) G140S (3) T60A (3) P23H (3) F11N (2) S1009A (2) H275Y (2) T733I (2) F1074L (2) I1307K (2) Q36W (2) G250E (2) S77Y (2) E28A (2) E28C (2) E28D (2) T66A (2) S1400C (2) S1400E (2) S1400D (2) L833F (2) D1790G (2) S1400G (2) S1400F (2) R334W (2) L8585R (2) I105V (2) N375S (2) V560G (2) A194T (2) T20S (2) T69D (2) T69S (2) Y93C (2) E138R (2) E138Q (2) F359V (2) R776H (2) Q422H (2) D110H (2) D110E (2) R753Q (2) R404C (2) C283Y (2) L31F (2) S252W (2) L460D (2) L33I (2) R140W (2) R140L (2) R140Q (2) V106I (2) V106M (2) E709K (2) V697L (2) P50I (2) P535H (2) P51S (2) G1314A (2) S492R (2) G308A (2) V191T (2) G71R (2) T215F (2) E56K (2) A2063G (2) D769H (2) L248V (2) E280A (2) Q21D (2) E504K (2) Q141K (2) R496H (2) S100P (2) T128N (2) L536R (2) L536Q (2) L536P (2) A143T (2) T97A (2) G3556C (2) K751Q (2) T4396G (2) V151L (2) G170R (2) A581G (2) L536H (2) G12R (2) L180M (2) W153Q (2) G193E (2) V173L (2) F876L (2) R479H (2) L82M (2) Q28D (2) G190E (2) R347H (2) K601E (2) G16R (2) R831C (2) G5271C (2) V75I (2) G681A (2) A270S (2) L63P (2) L869R (2) P236L (2) R831H (2) T13D (2) H1047L (2) C3670T (2) V34L (2) E255V (2) G469A (2) V57I (2) L144F (2) M233I (2) C825T (2) C8092A (2) G776C (2) G776V (2) F121Y (2) R172S (2) R172W (2) R172M (2) Q192R (2) R172G (2) E380Q (2) F166L (2) A200V (2) Y121F (2) G145R (2) K101P (2) R61C (2) V600M (2) F31I (2) K540E (2) K103H (2) R132V (2) D1270N (2) R1628P (2) R132S (2) V534E (2) R132G (2) R132L (2) V207I (2) K238N (2) G4655A (2) S112A (2) I169T (2) I84A (2) Y129S (1) G1388A (1) S77F (1) R20A (1) V140A (1) C686A (1) I1768V (1) E25K (1) K652E (1) C420R (1) S9304A (1) R337H (1) C421A (1) V189I (1) K304E (1) A7445G (1) D19H (1) L304P (1) Y454S (1) A133S (1) M9T (1) P596L (1) E318D (1) C1156Y (1) N171K (1) A7445C (1) V82F (1) G47A (1) R447H (1) G47E (1) V82L (1) R776C (1) A92T (1) E27Q (1) F1052V (1) P27A (1) A289T (1) L523S (1) H54Y (1) T1095C (1) S428F (1) R400C (1) D313Y (1) Q12M (1) R139C (1) A393T (1) W719R (1) T862I (1) T66K (1) T66I (1) G49A (1) R48G (1) H58C (1) D203E (1) I104F (1) K656E (1) T40S (1) D312N (1) L747P (1) G276T (1) L747S (1) R200W (1) I1171N (1) Q14D (1) S1400K (1) R115G (1) F17L (1) A71T (1) S339F (1) A71L (1) I431V (1) F317V (1) F317S (1) G20201A (1) F317C (1) G2545R (1) C377T (1) P243R (1) S9346A (1) R25L (1) L528M (1) Q222R (1) I22M (1) I107M (1) C1858T (1) L859R (1) G2032R (1) A859S (1) G389D (1) V148I (1) K65E (1) V148G (1) C242T (1) G389R (1) H369P (1) A98S (1) G2500A (1) I349V (1) I107V (1) V561D (1) C481R (1) L833V (1) P200T (1) G1051A (1) Y93F (1) Y414C (1) Y1248H (1) K65N (1) L74M (1) P4502C (1) Y1248C (1) Y1248D (1) F227R (1) V89L (1) T164I (1) H1124D (1) C94A (1) G1628A (1) A2215D (1) E200K (1) F227L (1) I305F (1) N682S (1) T1010I (1) I655V (1) R885H (1) G7444A (1) R776G (1) E354Q (1) A21443C (1) M351T (1) R620W (1) A54T (1) D594G (1) F311L (1) T49A (1) F116Y (1) H870R (1) G205S (1) E355G (1) R535H (1) I767M (1) L55M (1) E571K (1) L55R (1) M2540A (1) E92K (1) G238A (1) L838P (1) E6V (1) L814P (1) K509I (1) V21I (1) G699A (1) V167F (1) D949V (1) L33P (1) M66V (1) D61804R (1) R849W (1) V762A (1) D816H (1) V108M (1) V326L (1) V411L (1) L10D (1) L58H (1) E158K (1) N334K (1) A1067T (1) S1800A (1) G894T (1) G202A (1) C282T (1) I191V (1) G435A (1) K1060T (1) A10H (1) R272G (1) V654A (1) V106T (1) C1091T (1) I638F (1) P317R (1) V433M (1) S230R (1) N550H (1) R4E (1) P1058A (1) M244V (1) N550K (1) E709Q (1) G304A (1) T124A (1) S253N (1) M680I (1) G1316A (1) M552V (1) M552I (1) R182H (1) D835V (1) A871E (1) D835Y (1) A677G (1) C1950G (1) H1505R (1) A893S (1) L597Q (1) S2808A (1) N55H (1) K28M (1) D89E (1) A38G (1) L485W (1) M9346A (1) L159F (1) A437G (1) R92Q (1) V29C (1) L38V (1) G135C (1) A677V (1) C34T (1) G93R (1) R270H (1) V321A (1) C10D (1) G308V (1) R122W (1) D614G (1) H2507Q (1) D20W (1) G309A (1) G721A (1) G309E (1) I90P (1) C59R (1) C416R (1) G71A (1) Q61R (1) Q61L (1) H835L (1) R498L (1) V941L (1) Q62E (1) R389G (1) D769N (1) G156A (1) E1784K (1) G98T (1) Q65E (1) T92A (1) S239D (1) C656G (1) R451C (1) G73C (1) G5665T (1) R72P (1) F64L (1) L248R (1) M204I (1) R149S (1) A105G (1) M28L (1) D769Y (1) V769M (1) R75T (1) E193K (1) T890M (1) P250R (1) P58A (1) L532S (1) S147G (1) S1235R (1) K660E (1) T454A (1) R76K (1) L1213V (1) V742I (1) V1238I (1) R74W (1) T102C (1) K3048A (1) T93M (1) D961S (1) G1269A (1) R277W (1) P187S (1) Q20W (1) A561P (1) V740A (1) T783I (1) T674I (1) T783A (1) S8814A (1) V90I (1) C325G (1) Q188R (1) R30H (1) C785T (1) S100A (1) R496L (1) G174S (1) L798F (1) V765A (1) P11A (1) C18S (1) L798H (1) G1049R (1) V765M (1) S366T (1) R230C (1) G1376T (1) H396R (1) H396P (1) S65D (1) T1191I (1) A277G (1) L755A (1) H131R (1) T878A (1) T854A (1) P253R (1) C1494T (1) L755P (1) P120H (1) E525K (1) C102T (1) Y1253D (1) G196A (1) A145T (1) K70N (1) L861G (1) H43R (1) I76V (1) C344T (1) F1174V (1) R677W (1) S9313A (1) I112T (1) G10V (1) R10C (1) F1174L (1) R10A (1) K860I (1) R34P (1) F1174C (1) R108K (1) I112M (1) V151I (1) I332E (1) S1369A (1) R32Q (1) N409S (1) C563T (1) Q24H (1) I113T (1) D761Y (1) N291S (1) Y114C (1) V151A (1) G34A (1) G1069R (1) R896C (1) S567L (1) A827G (1) G12S (1) I54T (1) D565H (1) Y113H (1) P367L (1) R102G (1) R368H (1) M3002A (1) P125A (1) V282M (1) M1040E (1) E545G (1) E545A (1) G398A (1) E545D (1) G12A (1) L409P (1) S1787N (1) S784P (1) L841V (1) R14C (1) V943A (1) S9333A (1) Q148K (1) Q148E (1) M1043I (1) Y220C (1) T416P (1) A3669G (1) R38H (1) T961C (1) V1110L (1) T961G (1) L84F (1) S108N (1) C365Y (1) A719G (1) D237E (1) G37R (1) D104N (1) S653C (1) S786I (1) V834I (1) Y376C (1) G3514C (1) G594A (1) G1947A (1) G190C (1) V834L (1) Q546R (1) F522C (1) Q546L (1) Q546K (1) P699S (1) F2004L (1) D101H (1) T393C (1) A1330T (1) R988C (1) H48Q (1) T174M (1) A62V (1) G595R (1) A62T (1) L84V (1) M165I (1) V222A (1) P479L (1) G908R (1) Y318F (1) V75M (1) D101Y (1) I10F (1) D90V (1) H1112L (1) G269S (1) R3500Q (1) V30A (1) S282R (1) D919G (1) I665V (1) H1112Y (1) D90A (1) C385A (1) M95L (1) G1170S (1) V244M (1) G17T (1) S26E (1) N251K (1) W574C (1) G464V (1) C807T (1) V77I (1) Y449D (1) C168H (1) D4064A (1) M50I (1) Q215S (1) F106C (1) K56M (1) G465R (1) G598V (1) S769N (1) E586K (1) T1482I (1) L1196M (1) E148Q (1) T12W (1) S720P (1) Y641S (1) S768R (1) F129L (1) Y641N (1) C938A (1) C165V (1) R19C (1) C383R (1) Y641H (1) C805S (1) Y641F (1) W64R (1) Y641C (1) H1047Y (1) M1268T (1) A736V (1) C61G (1) P1009S (1) V481F (1) S1612C (1) Q546E (1) L718P (1) V179F (1) G106R (1) M1002A (1) P300D (1) S131F (1) N63L (1) W21C (1) L144S (1) M1149T (1) H558R (1) S373C (1) A69S (1) V1180L (1) V774A (1) T377M (1) V689M (1) V774M (1) D164V (1) L387M (1) R199W (1) N86S (1) M694V (1) N86Y (1) G11053T (1) R175H (1) T17M (1) Y86N (1) A2144G (1) A2059G (1) N345K (1) D50W (1) I180V (1) A864V (1) L24E (1) V118I (1) G212S (1) I843S (1) N1303K (1) R1623Q (1) A1033V (1) L1198F (1) N1325S (1) Q812R (1) V773M (1) G212A (1) A997T (1) S241T (1) E167K (1) G1764A (1) G80A (1) E62D (1) E274Q (1) M34T (1) G401S (1) A2142C (1) G1631D (1) G211A (1) D76Y (1) D76N (1) E384G (1) V249I (1) M1106C (1) L234I (1) L101I (1) A2143C (1) K806E (1) A687V (1) A119S (1) P1028S (1) A313G (1) D824V (1) S9C (1) C182A (1) S9G (1) S153F (1) S1900E (1) S1900D (1) S1900C (1) R1644H (1) S1900A (1) R702W (1) T1456G (1) T1565C (1) E1021K (1) K15210D (1) G779C (1) G82S (1) G779F (1) G840A (1) V18M (1) A27L (1) L28M (1) T351I (1) K121Q (1) L28P (1) H180Q (1) G779S (1) M11T (1) M11Q (1) P549S (1) N215S (1) G60D (1) R352W (1) G623R (1) G84E (1) E161K (1) G951A (1) C23S (1) E184K (1) V1206L (1) Y842C (1) V736A (1) L432V (1) E89Q (1) R135W (1) Y253F (1) G843D (1) D820Y (1) F77L (1) S311C (1) D10W (1) Y143H (1) G86R (1) Y143C (1) R112H (1) Y143A (1) A227G (1) K101Q (1) R463C (1) G85E (1) L236P (1) A310V (1) T798M (1) S310Y (1) R222C (1) A4917G (1) T798I (1) E44D (1) L302P (1) Q30R (1) L786V (1) R287Q (1) P286R (1) D36Y (1) R263Q (1) T599I (1) K103M (1) S680N (1) K1270A (1) R88Q (1) T224M (1) P46L (1) N700D (1) A5147S (1) E21G (1) Y822D (1) Q260A (1) Y188H (1) R131H (1) R1070Q (1) C316N (1) T81C (1) T1304M (1) I167V (1) I82A (1) D13H (1) Q54H (1) Q30H (1) L239R (1) Y823D (1) T117S (1) I84T (1) A222V (1) L106V (1) K432Q (1) G163S (1) I1370K (1) G163E (1) K650E (1) E757A (1) R399Q (1) G41S (1) C1895T (1) P392L (1) T334G (1) H274Y (1) R399G (1)

SNPMiner SNPMiner Trials (Home Page)


Report for Mutation C797S

Developed by Shray Alag, 2020-2021.
SNP Clinical Trial Gene

There are 14 clinical trials

Clinical Trials


1 A Phase 1 Study of Temozolomide in Combination With Targeted Therapy for NSCLC Patients With CNS Progression on Either Osimertinib or Lorlatinib

This trial is testing two novel combinations (temozolomide plus osimertinib OR temozolomide plus lorlatinib) which have not been evaluated in clinical trials. Thus, the exact benefits of these novel combinations are unclear. However, based on the mechanism of action of temozolomide and CNS(Central Nervous System) penetration/activity in other tumor types, it is hypothesized that adding temozolomide to osimertinib or temozolomide to lorlatinib may provide improvement in CNS disease control in patients with CNS progression on either of these latter two TKIs (Tyrosine kinase inhibitors).

NCT04541407
Conditions
  1. Non Small Cell Lung Cancer
  2. CNS Progression
Interventions
  1. Drug: Temozolomide plus Osimertinib
  2. Drug: Temozolomide plus Lorlatinib
MeSH:Disease Progression

Compound mutations are defined as 2 or more mutations in the EGFR tyrosine kinase domain with the following exceptions: 1. C797S and EGFR exon 19 deletion or EGFR exon 21 point mutation and 2. T790M mutation and EGFR exon 19 deletion or EGFR exon 21 point mutation. --- C797S ---

Primary Outcomes

Description: Adverse events will be determined by the common terminology criteria for adverse events version 5.0

Measure: Adverse events

Time: Up to 3.5 years

Secondary Outcomes

Description: Central Nervous System response rate according to the Response assessment in neuro-oncology (RANO) criteria per investigator assessment. Evaluable CNS lesions may not have been previously irradiated unless they are definitively progressing following radiation and prior to enrollment on the study.

Measure: CNS response rate

Time: Up to 3.5 years

Description: Extra-CNS response rate according to response evaluation criteria in solid tumors (RECIST) v1.1 per investigator assessment.

Measure: Extra-CNS response rate

Time: Up to 3.5 years

Description: Overall response rate including both RANO criteria for CNS response rate and RECIST v1.1 for extra-CNS response rate per investigator assessment.

Measure: Overall response rate

Time: Up to 3.5 years

Description: Incidence of improvement in neurological function on two successive exams when compared to baseline as determined by one of two study neuro-oncologists

Measure: Incidence of improvement in neurological function

Time: Up to 3.5 years

Description: PFS will be defined as time from enrollment until development of CNS progressive disease according to the RANO criteria, development of extra-CNS disease progression according to RECIST v1.1 or death.

Measure: Progression free survival (PFS)

Time: Up to 3.5 years

Description: CNS PFS will be defined as time from enrollment until development of CNS progressive disease per investigator assessment according to the RANO criteria or death.

Measure: CNS PFS

Time: Up to 3.5 years

Description: Extra-CNS PFS will be defined as time from enrollment until development of progressive disease outside the CNS per investigator assessment according RECIST v1.1 or death.

Measure: Extra-CNS PFS

Time: Up to 3.5 years

Description: OS will be defined as time from enrollment until death.Patients alive at date of end of study visit will be censored for survival.

Measure: Overall Survival

Time: Up to 3.5 years

2 Clinical Study of Yiqi-yangyin-jiedu Decoction Combined With Gefitinib in Advanced Pulmonary Adenocarcinoma Patients With Activating EGFR Mutation

The investigators performed a multi-centered, randomized, double blinded, placebo-controlled, prospective clinical trial on the effect of Yiqi-yangyin-jiedu decoction (YYJD), a chinese herbal medicine (CHM) formula combined with gefitinib to prolong the progression free survival (PFS) of advanced pulmonary adenocarcinoma patients with activating EGFR mutation (exon19del or exon21L858R). The investigators plan to enroll 198 cases in 3 years (99 cases for gefitinib, 99 cases for gefitinib plus YYJD), expecting that combination therapy has a better efficacy on prolonging PFS, overall survival, improving quality of life(QOL).

NCT02929693
Conditions
  1. Cancer
Interventions
  1. Drug: gefitinib
  2. Drug: Yiqi-yangyin-jiedu decoction
  3. Drug: placebo
MeSH:Adenocarcinoma Adenocarcinoma of Lung

Although AZD9291 (AstraZeneca), a third-generation EGFR-TKI is reported with a response rate of 61% in NSCLC patients with EGFR T790M and a mPFS of 9.6 months, resistance to third-generation inhibitors mediated by EGFR C797S mutation is inevitable. --- T790M --- --- C797S ---

Primary Outcomes

Description: Time from start of the study treatment to date of objective tumour progression (excluding clinical deterioration without evidence of objective progression).

Measure: Progression-free survival (PFS)

Time: 2 months

Secondary Outcomes

Description: interval time from the first date of randomization to that of death for any reason, the end of the study, or loss of follow-up

Measure: Overall survival (OS)

Time: 2 months

Description: The ORR (complete response (CR) plus partial response (PR)) was determined by the Response Evaluation Criteria In Solid Tumors (RECIST) (Eisenhauer et al, 2009) version 1.1.in Solid Tumors (RECIST1.1).

Measure: Objective response rate (ORR)

Time: 2 months

Description: QOL is assessed using Functional Assessment of Cancer therapy-lung (FACT-L) questionnaire .

Measure: Quality of life (QOL)

Time: 2 months

Description: Safety assessment is evaluated according to Common Toxicity Criteria (CTC 3.0).

Measure: Safety assessment evaluated according to Common Toxicity Criteria

Time: 2 months

3 MasterKey-01: A Phase 1/2, Open-label, Two-part, Multicenter Study to Assess the Safety, Tolerability, Pharmacokinetics & Antitumor Activity of BDTX-189, an Inhibitor of Allosteric ErbB Mutations, in Patients w/ Advanced Solid Malignancies

This is a clinical study with an orally administered drug, BDTX-189 in participants with advanced solid tumors that have select mutations or alterations in human epidermal growth factor receptor 2 (HER2/ErbB2) genes or epidermal growth factor receptor (EGFR/ErbB1). The main goals of this study are to: - Find the recommended dose of BDTX-189 that can be given safely to participants - Learn more about the side effects of BDTX-189 - Learn what the body does to BDTX-189 after it has been taken (pharmacokinetics or PK) - Determine the antitumor activity of BDTX-189 in participants with select allosteric ErbB gene mutations

NCT04209465
Conditions
  1. Solid Tumor
Interventions
  1. Drug: BDTX-189

Evidence of second- or third-degree atrioventricular block 2. Clinically significant arrhythmia (as determined by the Investigator) 3. QTcF interval of >470 msec - Leptomeningeal or untreated and/or symptomatic CNS malignancies (primary or metastatic) - Women who are pregnant or breast-feeding - Taking or unable to discontinue proton pump inhibitors within 1 week prior to baseline - Known concurrent KRAS mutation - Known tumor-harboring resistance mutations including EGFR T790M or C797S mutations or HER2 C805S mutation Phase 2 Only: - Prior documented treatment response to approved or investigational HER2 or EGFR tyrosine kinase inhibitor therapies Main Inclusion Criteria: - Histologically- or cytologically-confirmed locally advanced or metastatic solid tumor with documented recurrence or disease progression from standard anticancer therapy in the advanced/metastatic setting - No standard therapy available or standard therapy is considered unsuitable or intolerable according to the Investigator and consultation with the Medical Monitor Phase 1 Only: - Solid tumor patients with alterations that may be associated with antitumor activity based on preclinical data for BDTX-189 such as: 1. Allosteric HER2 or HER3 mutation(s) 2. EGFR or HER2 exon 20 insertion mutation(s) 3. HER2 amplified or overexpressing tumors 4. EGFR exon 19 deletion or L858R mutation Phase 2 Only: - Patients with a solid tumor harboring an: 1. Allosteric HER2 mutation (including but not limited to S310F/Y, R678Q, L755S/P, V777L, V842I) 2. EGFR or HER2 exon 20 insertion mutation Eligible mutations must be determined by a validated next-generation sequencing (NGS) test routinely used by each institution and performed in a CLIA-certified or equivalent laboratory. --- T790M --- --- C797S ---

Evidence of second- or third-degree atrioventricular block 2. Clinically significant arrhythmia (as determined by the Investigator) 3. QTcF interval of >470 msec - Leptomeningeal or untreated and/or symptomatic CNS malignancies (primary or metastatic) - Women who are pregnant or breast-feeding - Taking or unable to discontinue proton pump inhibitors within 1 week prior to baseline - Known concurrent KRAS mutation - Known tumor-harboring resistance mutations including EGFR T790M or C797S mutations or HER2 C805S mutation Phase 2 Only: - Prior documented treatment response to approved or investigational HER2 or EGFR tyrosine kinase inhibitor therapies Solid Tumor BDTX-189 is an irreversible, small molecular inhibitor that is highly selective versus wild-type EGFR and potent for cancer driver mutations of the ErbB family, including extracellular, transmembrane, and kinase domain allosteric mutations of HER2, as well as EGFR and HER2 exon 20 insertion mutations. --- T790M --- --- C797S ---

Primary Outcomes

Description: Certain toxicities will be considered dose-limiting unless clearly attributable to an extraneous cause, such as underlying disease.

Measure: Incidence of dose limiting toxicities as a determinant of the Recommended Phase 2 Dose (RP2D)

Time: After the first dose of treatment for up to 21 days.

Description: Objective response rate is defined as the proportion of participants who achieve a confirmed complete response (CR; disappearance of all target and non-target lesions) or partial response (PR; at least a 30% decrease from baseline in the sum of diameters of target lesions) per RECIST version 1.1.

Measure: Phase 2: Objective response rate as a measure of antitumor activity

Time: Assessed until disease progression or death for up to 12 months

Secondary Outcomes

Description: Adverse events will be assessed by National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.

Measure: Phase 1 and Phase 2: Incidence of treatment-emergent adverse events as a measure of safety and tolerability of BDTX-189

Time: From Cycle 1 Day 1 (each cycle is 21 days) until 30 days post last dose

Description: Blood samples will be taken to measure the plasma concentrations of BDTX-189 in both a fed and fasted state.

Measure: Phase 1 and Phase 2: Plasma concentration of BDTX-189 as a measure of pharmacokinetics

Time: Multiple time points during Cycles 1-4 (each cycle is 21 days)

Description: Objective response is defined as the proportion of participants who achieved a complete response (CR; disappearance of all target and non-target lesions) or partial response (PR; at least a 30% decrease from baseline in the sum of diameters of target lesions) per RECIST version 1.1.

Measure: Phase 1: Objective response rate as a preliminary measure of antitumor activity

Time: Assessed until disease progression or death for up to 12 months

Description: Duration of response is the time from first documentation of a response to first evidence of progressive disease per RECIST version 1.1 or death. A response is defined as either a complete response (CR; disappearance of all target lesions and non-target lesions) or partial response (PR; at least a 30% decrease in the sum of diameters of target lesions). Progressive disease is defined by a target lesion increase of 20% and at least 5mm from smallest on-study lesion sum, the appearance of new lesions, or unequivocal progression of non-target lesions.

Measure: Phase 1 and Phase 2: Duration of response as a measure of antitumor activity

Time: Assessed until disease progression or death for up to 12 months

Description: Disease control rate is defined as the proportion of participants achieving: a complete response (CR; disappearance of all target and non-target lesions), partial response (PR; at least a 30% decrease in the sum of diameters of target lesions), or stable disease (SD; neither sufficient shrinkage to qualify for a PR nor sufficient increase in lesions) per RECIST version 1.1.

Measure: Phase 1 and Phase 2: Disease control rate as a measure of antitumor activity

Time: Assessed until disease progression or death for up to 12 months

Description: Progression-free survival is the time from first study dose until disease progression (PD; target lesion increase of 20% and at least 5mm from smallest on-study lesion sum, the appearance of new lesions, or unequivocal progression of non-target lesions) per RECIST v1.1.

Measure: Phase 1 and Phase 2: Progression-free survival as a measure of antitumor activity

Time: Assessed until disease progression or death for up to 12 months

Description: Overall survival is the time from first study dose until death from any cause or study discontinuation.

Measure: Phase 2: Overall survival as a measure of clinical activity

Time: Assessed every 12 weeks after treatment discontinuation for up to 1 year

4 Prospective Observational Trial to Evaluate the Efficacy of the Combination of Osimertinib and Aspirin in Patients With Disease Progression to 3st Generation Epidermal Growth Factor Receptor-tyrosine Kinase Inhibitor(EGFR-TKI) Osimertinib

The third generation epidermal growth gactor receptor-tyrosine Kinase Inhibitor(EGFR-TKI) osimertinib has obvious curative effect for EGFR sensitive mutation and T790M mutation(PMID 27959700), but acquired drug resistance will occur. Previous studies show that apoptosis escape can lead to EGFR-TKI resistance.Osimertinib resistant cells show abnormal activation of PI3K/AKT/BIM activation(PMID 28765329). The classical drug aspirin can effectively decrease AKT phosphorylation and activate of BIM(PMID 28881293).So Investigators speculate that aspirin may decrease the PI3K/AKT/BIM signaling pathways, then promote osimertinib resistant cells apoptosis. The current study aims to evaluate the combination of aspirin and osimertinib in patients with EGFR/T790M mutations.

NCT03532698
Conditions
  1. Non-Small Cell Lung Cancer Stage IIIB
  2. Non-small Cell Lung Cancer Stage IV
  3. EGFR T790M
Interventions
  1. Drug: Aspirin
  2. Drug: Osimertinib
MeSH:Lung Neoplasms Carcinoma, Non-Small-Cell Lung
HPO:Neoplasm of the lung Non-small cell lung carcinoma

Previous study showed that one principal mechanism accounting for majority of acquired resistance to Osimertinib in lung cancer is mediated by an exon 20 C797S mutation etc(PMID 29596911). --- C797S ---

Primary Outcomes

Description: To evaluate the response to therapy and Objective Response Rate of the combination of Osimertinib and Aspirin in patients who has metastatic pulmonary adenocarcinoma disease progression to 3st generation EGFR-TKI Osimertinib.

Measure: Objective Response Rate(ORR) according to resist 1.1

Time: 2years

Secondary Outcomes

Description: To evaluate the response to therapy and disease control rate of the combination of Osimertinib and Aspirin in patients who has metastatic pulmonary adenocarcinoma disease progression to 3st generation EGFR-TKI Osimertinib.

Measure: disease control rate(DCR) according to resist 1.1

Time: 2years

Description: To evaluate the response to therapy and Time to progression of the combination of Osimertinib and Aspirin in patients who has metastatic pulmonary adenocarcinoma disease progression to 3st generation EGFR-TKI Osimertinib.

Measure: Time to progression(TTP) according to resist 1.1

Time: 2years

Description: To evaluate the response to therapy and duration of Response of the combination of Osimertinib and Aspirin in patients who has metastatic pulmonary adenocarcinoma disease progression to 3st generation EGFR-TKI Osimertinib.

Measure: duration of Response(DOR) according to resist 1.1

Time: 2years

5 Phase I Study to Evaluate Safety, Tolerability, Pharmacokinetics and Anti-Tumor Activity of WSD0922-FUFU

This phase I trial studies the side effects and best dose of WSD0922-FU for the treatment of glioblastoma, anaplastic astrocytoma, or non-small cell lung cancer that has spread to the central nervous system (central nervous system metastases). WSD0922-FU is a targeted treatment which blocks the EGFR protein - a strategy that has led to a lot of benefit in patients with many different cancers. WSD0922-FU may also be able to get into cancers in the brain and spinal cord and help patients with brain and spinal cord cancers.

NCT04197934
Conditions
  1. Anaplastic Astrocytoma, IDH-Wildtype
  2. Glioblastoma, IDH-Wildtype
  3. Lung Non-Small Cell Carcinoma
  4. Metastatic Malignant Neoplasm in the Central Nervous System
  5. Metastatic Malignant Neoplasm in the Leptomeninges
Interventions
  1. Drug: EGFR/EGFRvIII Inhibitor WSD0922-FU
  2. Procedure: Therapeutic Conventional Surgery
MeSH:Neoplasms Glioblastoma Astrocytoma Neoplasms, Second Primary Carcinoma, Non-Small-Cell Lung
HPO:Astrocytoma Glioblastoma multiforme Neoplasm Non-small cell lung carcinoma Subependymal giant-cell astrocytoma

Patients are not considered to have a "currently active" malignancy if they have completed therapy and are free of disease for more than three years prior to registration - Any of the following cardiac criteria: - A marked baseline prolongation of QT/corrected QT (QTc) interval - (e.g., repeated demonstration of a QTc interval > 480 milliseconds (ms) (Common Terminology Criteria for Adverse Events [CTCAE] grade 1) using Fridericia's QT correction formula - A history of additional risk factors for torsade de pointes (TdP) (e.g., heart failure, hypokalemia, family history of long QT syndrome) - The use of concomitant medications that prolong the QT/QTc interval - Patients confirmed to have a cis double mutation (Del19/T790M or L858R/T790M) or cis triple mutation (Del19/T790m/C797S or L858R/T790M/C797S) - Past medical history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease. --- T790M --- --- L858R --- --- C797S ---

Primary Outcomes

Description: The RP2D is either the maximum tolerated dose (MTD) or the highest dose tested (in the case that none of the doses are deemed higher than the MTD), whichever is higher.

Measure: Recommended phase 2 dose

Time: Up to 28 days

Secondary Outcomes

Measure: Incidence of adverse events

Time: Up to 4-6 weeks after study completion

Description: The overall response rate will be defined as the number of patients with a partial response (PR) or better that is confirmed in consecutive evaluations (at least 8 weeks apart) divided by the total number of evaluable patients. A 95% confidence interval will also be constructed using the properties of the binomial distribution.

Measure: Overall response rate

Time: Up to 5 years

Description: Duration of response is defined as the number of days between a patient's first occurrence of a PR (or better) and progression. If a patient goes off study prior to progression (for another reason) then they will be censored at that time. A time to event analysis will be performed utilizing the Kaplan-Meier method which will yield a median DOR.

Measure: Duration of response (DOR)

Time: From the first occurrence of a PR (or better) and progression, assessed up to 5 years

Description: A patient's progression free survival time is the number of days between study entry and disease progression. These data will be analyzed utilizing the Kaplan-Meier method which will yield a median PFS time.

Measure: Progression Free Survival (PFS)

Time: From study entry to disease progression, assessed up to 5 years

Other Outcomes

Measure: Maximum plasma Concentration [Cmax] of WSD0922-FU after a single dose of WSD0922-FU

Time: Cycle 1 Day 1: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 and 24 hours

Measure: Area under the plasma concentration versus time curve (AUC) of WSD022-FU after a single dose of WSD0922-FU

Time: Pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours of day 1 of cycles 1 and 2; and pre-dose day 1 of cycles 3 and 4

Measure: Maximum plasma Concentration [Cmax] of WSD0922-FU after multiple doses of WSD0922-FU

Time: Cycle 1 Day 15: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10 and 12 hours

Measure: Area under the plasma concentration versus time curve (AUC) of WSD022-FU after multiple doses of WSD0922-FU

Time: Cycle 1 Day 15: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10 and 12 hours

Measure: CSF concentration of WSD0922-FU after multiple doses of WSD0922-FU (Dose Expansion - NSCLC leptomeningeal metastases (NSCLC LM) cohort only).

Time: Cycle 2 Day 1

Measure: Brain tumor concentration of WSD0922-FU after a single dose of WSD0922-FU (Dose Expansion - Brain tumor penetration (BTP) cohort only).

Time: Cycle 0 Day 1

Measure: Tumor EGFR inhibition after a single dose of WSD0922-FU (Dose Expansion - Brain tumor penetration (BTP) cohort only).

Time: Cycle 0 Day 1

Measure: Effect of food on Maximum plasma Concentration [Cmax] of WSD0922-FU after a single dose of WSD0922-FU (Dose Expansion - NSCLC LM cohort only).

Time: Cycle 0 Day 1 and Cycle 0 Day 4

Measure: Effect of food on Area under the plasma concentration versus time curve (AUC) of WSD022-FU after a single dose of WSD0922-FU (Dose Expansion - NSCLC LM cohort only).

Time: Cycle 0 Day 1 and Cycle 0 Day 4

6 Prospective Observational Trial to Evaluate the Efficacy of the Combination of Osimertinib and Aspirin in Patients With Epidermal Growth Factor Receptor(EGFR)-Mutation

The third generation epidermal growth factor receptor-tyrosine Kinase Inhibitor(EGFR-TKI) osimertinib has obvious curative effect for EGFR sensitive mutation and T790M mutation(PMID 27959700), but acquired drug resistance will occur. Previous studies show that apoptosis escape can lead to EGFR-TKI resistance.Osimertinib resistant cells show abnormal activation of PI3K/AKT/BIM activation(PMID 28765329). The classical drug aspirin can effectively decrease AKT phosphorylation and activate of BIM(PMID 28881293).So Investigators speculate that aspirin may decrease the PI3K/AKT/BIM signaling pathways, then promote osimertinib resistant cells apoptosis. The current study aims to evaluate the combination of aspirin and osimertinib in patients with EGFR/T790M mutations.

NCT04184921
Conditions
  1. Lung Cancer Non-small Cell Stage IV
Interventions
  1. Drug: Aspirin 100mg
  2. Drug: Osimertinib 80 MG
MeSH:Carcinoma, Non-Small-Cell Lung
HPO:Non-small cell lung carcinoma

Previous study showed that one principal mechanism accounting for majority of acquired resistance to Osimertinib in lung cancer is mediated by an exon 20 C797S mutation etc(PMID 29596911). --- C797S ---

Primary Outcomes

Description: To evaluate the response to therapy and progression-free survival rate of the combination of Osimertinib and Aspirin in advanced lung cancer patients who has EGFR-mutation.

Measure: progression-free survival rate according to resist 1.1

Time: 2 years

Secondary Outcomes

Description: To evaluate the overall survival of the combination of Osimertinib and Aspirin in advanced lung cancer patients who has EGFR-mutation.

Measure: overall survival(OS)

Time: 5 years

Description: To evaluate the response to therapy and Objective Response Rate of the combination of Osimertinib and Aspirin in patients who has EGFR-mutation.

Measure: Objective Response Rate(ORR) according to resist 1.1

Time: 2 years

Description: To evaluate the response to therapy and Time to progression of the combination of Osimertinib and Aspirin in patients who has EGFR-mutation.

Measure: Time to progression(TTP) according to resist 1.1

Time: 2 years

7 Prospective Observational Trial to Evaluate the Efficacy of the Combination of Osimertinib and Aspirin in Patients With Disease Progression to 1st Generation EGFR-TKI Due to Acquisition of EGFR T790M

The third generation epidermal growth gactor receptor-tyrosine Kinase Inhibitor(EGFR-TKI) osimertinib has obvious curative effect for EGFR sensitive mutation and T790M mutation(PMID 27959700), but acquired drug resistance will occur. Previous studies show that apoptosis escape can lead to EGFR-TKI resistance.Osimertinib resistant cells show abnormal activation of PI3K/AKT/BIM activation(PMID 28765329). The classical drug aspirin can effectively decrease AKT phosphorylation and activate of BIM(PMID 28881293).So Investigators speculate that aspirin may decrease the PI3K/AKT/BIM signaling pathways, then promote osimertinib resistant cells apoptosis. The current study aims to evaluate the combination of aspirin and osimertinib in patients with EGFR/T790M mutations.

NCT03543683
Conditions
  1. Non-Small Cell Lung Cancer Stage IIIB
  2. Non-small Cell Lung Cancer Stage IV
  3. EGFR T790M
Interventions
  1. Drug: Osimertinib
  2. Drug: Aspirin
MeSH:Lung Neoplasms Carcinoma, Non-Small-Cell Lung
HPO:Neoplasm of the lung Non-small cell lung carcinoma

Previous study showed that one principal mechanism accounting for majority of acquired resistance to Osimertinib in lung cancer is mediated by an exon 20 C797S mutation etc(PMID 29596911). --- C797S ---

Primary Outcomes

Description: To evaluate the response to therapy and 1 year median progression-free survival(PFS) rates of the combination of Osimertinib and Aspirin in patients who harbors T790M EGFR-mutant with metastatic pulmonary adenocarcinoma disease progression to 1st generation EGFR-TKI .

Measure: 1-year median progression-free survival(PFS) rates according to resist 1.1

Time: 3years

Secondary Outcomes

Description: To evaluate the response to therapy and 1 year progression-free survival (PFS) of the combination of Osimertinib and Aspirin in patients who harbors T790M EGFR-mutant with metastatic pulmonary adenocarcinoma disease progression to 1st generation EGFR-TKI .

Measure: median PFS according to resist 1.1

Time: 3years

Description: To evaluate the response to therapy and overall survival(OS) of the combination of Osimertinib and Aspirin in patients who harbors T790M EGFR-mutant with metastatic pulmonary adenocarcinoma disease progression to 1st generation EGFR-TKI

Measure: median overall survival(OS) according to resist 1.1

Time: 3years

8 Whole Genomic Landscape of EGFR Mutation-Positive Advanced Non-Small Cell Lung Cancer Treated With First-Line Osimertinib (WARRIOR)

This is a phase 2 single-arm, non-randomized multicentre and tissue acquisition study to evaluate acquired resistance mechanisms, efficacy, and safety in advanced, EGFR tyrosine kinase inhibitor-naïve NSCLC patients with EGFR-activating mutations who receive a first-line osimertinib orally at a dose of 80mg once daily.

NCT03969823
Conditions
  1. Locally Advanced or Metastatic NSCLC
Interventions
  1. Drug: Tagrisso
MeSH:Carcinoma, Non-Small-Cell Lung
HPO:Non-small cell lung carcinoma

Acquired resistance to first-line osimertinib is mediated by heterogeneous mechanisms including MET amplification (15%), secondary EGFR mutation including C797S or S768I (7%), PIK3CA mutation (7%), CDK4/6 amplification (5%), KRAS mutation (3%), BRAF mutation (3%), CCND1-3 amplification (3%), CCNE1 amplification (2%), HER2 amplification (2%), and SPTBN1-ALK fusion (1%) using plasma genotyping of FLAURA study (N=91). --- C797S ---

Primary Outcomes

Description: Disease progression as defined by investigator assessments according to RECIST1.1

Measure: Proportion of acquired resistance mechanisms to osimertinib at disease progression

Time: Through study completion, an average of 2 years

Secondary Outcomes

Description: AEs/SAEs as defined by NCI CTCAE version 5.0

Measure: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]

Time: Through study completion, an average of 2 years

Description: PFS as defined as the time from the date of initiation until the date of first documented progression

Measure: Progression-Free Survival (PFS)

Time: Through study completion, an average of 2 years

Description: OS as defined as the time from the date of first dose until death due to any cause

Measure: Overall Survival (OS)

Time: Through study completion, an average of 2 years

Description: ORR using investigator assessments according RECIST1.1

Measure: Objective Response Rate (ORR)

Time: Through study completion, an average of 2 years

9 A Multi-center, One-arm, Phase II Trial of Anlotinib Combined With Osimertinib as the Second-line Treatment in Stage IIIb-IV NSCLC With Confirmed EGFRm and T790M.

Evaluate the efficacy and safety of Anlotinib combined with Icotinib as the second-line treatment in stage IIIb-IV NSCLC patients with sensitive EGFR and T790M mutations.

NCT04029350
Conditions
  1. Non Small Cell Lung Cancer
Interventions
  1. Drug: Anlotinib Combined With Osimertinib
MeSH:Carcinoma, Non-Small-Cell Lung
HPO:Non-small cell lung carcinoma

Exclusion Criteria: 1. Squamous cell carcinoma (including adenosquamous carcinoma); Small Cell Lung Cancer (including small cell cancer and other kinds of cancer mixed with non-small cell cancer) 2. Non-small cell lung cancer (NSCLC) with an EGFR C797S mutation. --- C797S ---

Primary Outcomes

Description: The PFS time is defined as time from enrollment to locoregional or systemic recurrence, second malignancy or death due to any cause; censored observations will be the last date of : "death", "last tumor assessment", "last follow up date" or "last date in drug log"

Measure: Progression-free survival (PFS)

Time: each 42 days up to PD or death (up to 24 months)

Secondary Outcomes

Description: OS was defined as time from date of enrollment to date of death due to any cause. For participants still alive at the time of analysis, OS time was censored on last date that participants were known to be alive.

Measure: OS(Overall Survival)

Time: up to 24 months

Description: To evaluate the effectiveness of Anlotinib Hydrochloric Capsule Plus Icotinib Hydrochloric Tablet by enhanced CT/MRI scan every two cycles. Objective Response Rate (ORR) is defined as participants who had complete response (CR) or partial response(PR) divided by the total number of patients.

Measure: ORR(Objective Response Rate)

Time: each 42 days up to intolerance the toxicity or PD (up to 24 months)

Description: To evaluate the effectiveness of Anlotinib Hydrochloric Capsule Plus Icotinib Hydrochloric Tablet by enhanced CT/MRI scan every two cycles. Disease Control Rate (DCR) defined as the percentage of participants with Disease Control best overall response (complete response, partial response or stable disease).

Measure: DCR(Disease Control Rate)

Time: each 42 days up to intolerance the toxicity or PD (up to 24 months)

Description: Number of Participants with Adverse Events as a Measure of Safety and Tolerability

Measure: Adverse Events

Time: Until 30 day safety follow-up visit

10 A Study of T790M Mutation Testing in Patient Tissue and Blood With Various Detection Platforms at Hospital Laboratories in Comparison With Central Testing

The study primary objective is to assess the concordance of T790M resistance mutation testing from hospital-based laboratories with T790M resistance mutation testing from a central laboratory.

NCT02991274
Conditions
  1. Locally Advanced or Metastatic EGFR(+) NSCLC Patients
Interventions
  1. Procedure: genomic testing of T790M mutation

The prevalence of C797S (An amino acid substitution at position 797 in EGFR, from a Cysteine (C) to a Serine (S) ) resistance mutation based on the local lab testing. --- C797S ---

Prevalence (%) = (number of patients with C797S mutation positive)/(total number of patients with evaluable C797S testing)×100%. --- C797S ---

Prevalence (%) = (number of patients with C797S mutation positive)/(total number of patients with evaluable C797S testing)×100%. --- C797S --- --- C797S ---

Primary Outcomes

Description: Concordance (%)=(number of patients with same T790M mutation status based on central and local labs)/(total number of patients in the FAS) ×100%

Measure: the concordance of T790M mutation testing between the test in central and local labs

Time: within 1 -14 days after enrolled

Secondary Outcomes

Description: Prevalence (%) = (number of patients with T790M mutation positive)/(total number of patients in the FAS)×100%

Measure: The prevalence rate of T790M mutation based on the central lab testing

Time: within 1 -14 days after enrolled

Description: Sensitivity (%)=(number of patients with T790M mutation positive based on both tissue and plasma tests)/(number of patients with T790M mutation positive based on tissue test) ×100%

Measure: The sensitivity of each platform based on the local lab plasma testing

Time: within 1 -14 days after enrolled

Description: Specificity (%)=(number of patients with T790M mutation negative based on both tissue and plasma tests)/(number of patients with T790M mutation negative based on tissue test) ×100%

Measure: The Specificity of each platform based on the local lab plasma testing

Time: within 1 -14 days after enrolled

Description: Positive predictive value (%)=(number of patients with T790M mutation positive based on both tissue and plasma tests)/(number of patients with T790M mutation positive based on plasma test) ×100%

Measure: The Positive predictive value of each platform based on the local lab plasma testing

Time: within 1 -14 days after enrolled

Description: Negative predictive value (%)=(number of patients with T790M mutation negative based on both tissue and plasma tests)/(number of patients with T790M mutation negative based on plasma test) ×100%

Measure: The Negative predictive value of each platform based on the local lab plasma testing

Time: within 1 -14 days after enrolled

Description: Concordance (%)=(number of patients with same T790M mutation status based on tissue and plasma tests)/(total number of patients in the FAS) ×100%

Measure: The Concordance of each platform based on the local lab testing

Time: within 1 -14 days after enrolled

Description: Prevalence (%) = (number of patients with C797S mutation positive)/(total number of patients with evaluable C797S testing)×100%

Measure: The prevalence of C797S (An amino acid substitution at position 797 in EGFR, from a Cysteine (C) to a Serine (S) ) resistance mutation based on the local lab testing

Time: within 1 -14 days after enrolled

Description: Prevalence (%) = (number of patients with rare EGFR mutation positive)/(total number of patients in the FAS)×100%

Measure: Rare EGFR mutation prevalence rate

Time: within 1-14 days after enrolled

11 Detect EGFR T790M Mutation in ctDNA of Chinese Advanced/Metastatic NSCLC Patients by Cobas, Super-ARMS, Digital PCR and NGS and Evaluate Clinical Outcomes of T790M Mutation Positive Patients Who Had AZD9291 Monotherapy

The aim of this study is to evaluate concordance of T790M mutation plasma testing between the Cobas test and each of other platforms: Super-ARMS, digital PCR or NGS. And to assess the efficacy of AZD9291 monotherapy by assessment of PFS in adult patients with advanced or metastatic NSCLC, who have received prior EGFR-tyrosine kinase inhibitor (TKI) therapy and are T790M mutation positive detected by any one of the four plasma testing platforms: Cobas/Super-ARMS/ digital PCR/NGS.

NCT02997501
Conditions
  1. Lung Cancer
Interventions
  1. Procedure: T790M+ Testing
  2. Procedure: Baseline Visit Blood & Urine Testing
  3. Procedure: Baseline ECG
  4. Procedure: Visual Slit-Lamp Testing
  5. Drug: AZD9291 Dosing
  6. Procedure: Plasma AZD9291 testing

To evaluate the NPV of Super-ARMS/digital PCR/NGS by using Cobas as the reference.. Proportion of patients with each EGFR mutation (C797S and T790M etc.) at different time point.. --- C797S ---

Primary Outcomes

Description: To evaluate concordance of T790M mutation plasma testing between the Cobas test and Super-ARMS platform.

Measure: Concordance of T790M mutation plasma testing between Cobas test and Super-ARMS platform

Time: Within 1- 28 days after enrollment and before study treatment

Description: To assess the efficacy of AZD9291 monotherapy by assessment of PFS in adult patients with advanced or metastatic NSCLC, who have received prior EGFR- TKI therapy and are T790M mutation positive detected by any one of the four plasma testing platforms: Cobas/Super-ARMS/ digital PCR/NGS.

Measure: Progression Free Survival (PFS) using investigator assessments according to RECIST v1.1

Time: From first dose intake to Progression of disease (PD), up to 3 years

Description: To evaluate concordance of T790M mutation plasma testing between the Cobas test and digital PCR platform.

Measure: Concordance of T790M mutation plasma testing between Cobas test and digital PCR platform

Time: Within 1- 28 days after enrollment and before study treatment

Description: To evaluate concordance of T790M mutation plasma testing between the Cobas test and NGS platform.

Measure: Concordance of T790M mutation plasma testing between Cobas test and NGS platform

Time: Within 1- 28 days after enrollment and before study treatment

Secondary Outcomes

Description: To evaluate the sensitivity of Super-ARMS/digital PCR/NGS by using Cobas as the reference.

Measure: Testing sensitivity

Time: Within 1- 28 days after enrollment and before study treatment

Description: To assess the efficacy of AZD9291 monotherapy by assessment of ORR in adult patients with advanced or metastatic NSCLC, who have received prior EGFR-TKI therapy and are T790M mutation positive detected by any one of the four plasma testing platforms: Cobas/Super-ARMS/ digital PCR/NGS.

Measure: Objective Response Rate (ORR)

Time: From first dose intake to end of study, up to 3 years

Description: To assess the efficacy of AZD9291 monotherapy by assessment of OS in adult patients with advanced or metastatic NSCLC, who have received prior EGFR-TKI therapy and are T790M mutation positive detected by any one of the four plasma testing platforms: Cobas/Super-ARMS/ digital PCR/NGS.

Measure: Overall Survival (OS)

Time: From first dose intake to end of study, up to 3 years

Description: To evaluate the specificity of Super-ARMS/digital PCR/NGS by using Cobas as the reference.

Measure: Testing specificity

Time: Within 1- 28 days after enrollment and before study treatment

Description: To evaluate PPV of Super-ARMS/digital PCR/NGS by using Cobas as the reference.

Measure: Testing positive predictive value (PPV)

Time: Within 1- 28 days after enrollment and before study treatment

Description: To evaluate the NPV of Super-ARMS/digital PCR/NGS by using Cobas as the reference.

Measure: Testing negative predictive value (NPV)

Time: Within 1- 28 days after enrollment and before study treatment

Other Outcomes

Description: To dynamically monitor EGFR mutations by NGS and digital PCR in ctDNA of patients receiving AZD9291 treatment.

Measure: Proportion of patients with each EGFR mutation (C797S and T790M etc.) at different time point.

Time: every 6 weeks during treatment, up to 3 years

Description: To explore the mechanisms of acquired resistance in patients who received AZD9291 treatment by NGS testing of tissue and/or blood samples from the collection at PD versus baseline.

Measure: Changes of distribution of resistance related genes at PD compared with baseline.

Time: every 6 weeks during treatment, up to 3 years

Description: To describe the genomic profile of long-term survivors, especially to find out potential genomic prognosis and/or predictive factors for AZD9291 long-term efficacy as compared to rapid PD patients.

Measure: Key genetic and proteomic markers including, but not limited to, EGFR mutations

Time: every 6 weeks during treatment, up to 3 years

Description: To evaluate concordance of EGFR mutation plasma testing by Bio-rad droplet digital PCR using other plasma test or tissue test as reference, respectively.

Measure: Testing concordance

Time: Within 1- 28 days after enrollment and before study treatment

Description: To evaluate sensitivity of EGFR mutation plasma testing by Bio-rad droplet digital PCR using other plasma test or tissue test as reference, respectively.

Measure: Testing sensitivity

Time: Within 1- 28 days after enrollment and before study treatment

Description: To evaluate specificity of EGFR mutation plasma testing by Bio-rad droplet digital PCR using other plasma test or tissue test as reference, respectively.

Measure: Testing specificity

Time: Within 1- 28 days after enrollment and before study treatment

Description: To evaluate PPV of EGFR mutation plasma testing by Bio-rad droplet digital PCR using other plasma test or tissue test as reference, respectively.

Measure: Testing positive predictive value (PPV)

Time: Within 1- 28 days after enrollment and before study treatment

Description: To evaluate NPV of EGFR mutation plasma testing by Bio-rad droplet digital PCR using other plasma test or tissue test as reference, respectively.

Measure: Testing negative predictive value (NPV)

Time: Within 1- 28 days after enrollment and before study treatment

Description: To evaluate the efficacy of patients who receive AZD9291 monotherapy and are T790M mutation positive detected by each of the five platforms, respectively.

Measure: Objective Response Rate (ORR)

Time: From first dose intake to end of study, up to 3 years

Description: To evaluate the efficacy of patients who receive AZD9291 monotherapy and are T790M mutation positive detected by each of the five platforms, respectively.

Measure: Progression Free Survival (PFS)

Time: From first dose intake to end of study, up to 3 years

Description: To evaluate the efficacy of patients who receive AZD9291 monotherapy and are T790M mutation positive detected by each of the five platforms, respectively.

Measure: Overall Survival (OS)

Time: From first dose intake to end of study, up to 3 years

12 A Pilot Study of Local Ablative Therapy for Treatment of Oligoprogressive, EGFR-mutated, Non-Small Cell Lung Cancer (NSCLC) After Treatment With Osimertinib (AZD9291, Tagrisso)

Background: Some non-small-cell lung cancers (NSCLC) have a mutation in a gene that makes a protein called EGFR. This particular cancer can be treated with certain drugs such as Erlotinib (Tarceva), Gefitinib (Iressa) and Osimertinib (Tagrisso). But many tumors become resistant to these drugs because of a second mutation. Researchers want to test if adding local ablative therapy (LAT) extends the benefits of the drug, Osimertinib. LAT can include techniques such as surgery, radiofrequency ablation, cryotherapy or radiation therapy. Objective: To test if re-taking osimertinib after LAT is safe, tolerable, and effective for people whose NSCLC has progressed after initial treatment with osimertinib. Eligibility: Adults ages 18 and older with certain types of NSCLC. Participants will be divided into various groups as described below. Design: Participants will be screened with: Medical history Physical exam Blood, urine, and heart tests Tumor scans Eye exam Review of tumor sample. Participants will take the study drug by mouth once a day. They will continue until they can no longer tolerate it or their disease worsens. They will keep a dosage diary. All participants will start each 21-day course with physical exam; blood, urine, and saliva tests; and electrocardiogram. They will have scans every 6 weeks and echocardiogram every 3 months. Groups 1 and 2 will: Start osimertinib right away. Have LAT if their disease gets worse and is suitable for LAT. If LAT cannot be performed or LAT consists of a procedure other than surgery, a tumor biopsy will be performed. Re-start osimertinib after LAT, or other treatments if not suitable for LAT. Group 3 will: Have LAT. If LAT consists of a procedure other than surgery, a tumor biopsy will be performed. Start osimertinib after LAT. After participants stop taking the drugs, they will have a final visit. This will include: Medical history Physical exam Heart and blood tests Participants will be called every year for follow-up.

NCT02759835
Conditions
  1. Lung Adenocarcinoma
  2. Lung Neoplasms
Interventions
  1. Drug: osimertinib
  2. Other: LAT
MeSH:Lung Neoplasms Adenocarcinoma of Lung
HPO:Neoplasm of the lung

In fact, a newly identified EGFR mutation (C797S) that results in acquired resistance to osimertinib has been reported recently. --- C797S ---

Primary Outcomes

Description: progression-free survival (PFS)

Measure: determine PFS in patients with oligoprogressive disease after treatment with LAT followed by osimertinib

Time: progression of disease

Description: time to second progression (PFS2)

Measure: Patients who progress on their initial treatment with osimertinib and receive LAT therapy (surgery, radiation therapy, or RFA) followed by osimertinib will be evaluated for their time to second progression (PFS2)

Time: progression of disease

Secondary Outcomes

Description: response rate

Measure: response rate

Time: end of treatment

Description: overall survival

Measure: overall survival

Time: death

Description: EGFR mutation status using liquid biopsies

Measure: feasibility of evaluating EGFR mutation status using liquid biopsies

Time: end of treatment

13 A Phase 1, First-in-Human, Open-Label, Dose Escalation Study of JNJ-61186372, a Human Bispecific EGFR and cMet Antibody, in Subjects With Advanced Non-Small Cell Lung Cancer

The purpose of study is to evaluate the safety, pharmacokinetics, and preliminary efficacy of Amivantamab as a monotherapy and in combination with lazertinib, and to determine the recommended Phase 2 dose (RP2D) (monotherapy), recommended Phase 2 combination dose (RP2CD) (combination therapy), and to determine recommended Phase 2 Dose (RP2q3W) with combination chemotherapy (Amivantamab in combination with standard of care carboplatin and pemetrexed) in 21 day treatment cycle for participants with advanced non-small cell lung cancer (NSCLC).

NCT02609776
Conditions
  1. Non-Small-Cell Lung Cancer
Interventions
  1. Drug: Amivantamab
  2. Drug: Amivantamab
  3. Drug: Lazertinib
  4. Drug: Carboplatin
  5. Drug: Pemetrexed
MeSH:Lung Neoplasms Carcinoma, Non-Small-Cell Lung
HPO:Neoplasm of the lung Non-small cell lung carcinoma

Cohort C: Participants with primary EGFR mutated disease, with a documented EGFR alteration (example, C797S) mediating resistance to previous treatment with a third generation EGFR TKI (for example, osimertinib), in participants with primary Exon 20ins disease, the documented EGFR alteration may arise following treatment with a TKI with known activity against Exon 20ins disease (for example, poziotinib). --- C797S ---

Primary Outcomes

Description: The Dose Limiting Toxicity (DLT) is based on drug related adverse events and includes unacceptable hematologic toxicity, non-hematologic toxicity of Grade 3 or higher, or elevations in hepatic enzymes suggestive of drug-induced liver injury.

Measure: Part 1: Number of Participants With Dose Limiting Toxicity (DLT)

Time: Up to Day 28

Description: An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.

Measure: Part 2: Number of Participants With Adverse Events (AEs) and Serious AEs

Time: Screening up to follow-up (30 [+7] days after the last dose)

Description: Overall response rate (ORR) is defined as the percentage of participants who achieve either a CR or PR as per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1). CR: disappearance of all target lesions and non-target lesions. All lymph nodes must be non-pathological in size (< 10 mm short axis) and normalisation of tumour marker levels; PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters and Persistence of one or more non-target lesion(s) and/or maintenance of tumour marker level above the normal limits.

Measure: Part 2: Overall Response Rate (ORR)

Time: Up to End of Treatment Follow (EOT) Up Period (30 [+7] days after the last dose)

Description: DOR will be calculated as time from initial response of CR (disappearance of all target lesions and non-target lesions. All lymph nodes must be non-pathological in size ([<] 10 [mm] short axis) and normalisation of tumour marker levels) or PR (at least a 30 [%] decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters and persistence of one or more non-target lesion(s) and/or maintenance of tumour marker level above the normal limits or durable stable disease (neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum diameters while on study and persistence of one or more non-target lesion(s) and/or maintenance of tumour marker level above the normal limits) to progressive disease (PD) or death due to underlying disease, whichever comes first, only for participants who achieve CR or PR.

Measure: Part 2: Duration of Response (DOR)

Time: Up to EOT Follow Up Period (30 [+7] days after the last dose)

Description: Clinical benefit rate is defined as the percentage of participants achieving complete response (CR): disappearance of all target lesions and non-target lesions. All lymph nodes must be non-pathological in size (less than [<] 10 millimeter [mm] short axis) and normalisation of tumour marker levels or partial response (PR): at least a 30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters and persistence of one or more non-target lesion(s) and/or maintenance of tumour marker level above the normal limits or durable stable disease (neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum diameters while on study and persistence of one or more non-target lesion(s) and/or maintenance of tumour marker level above the normal limits.

Measure: Part 2: Percentage of Participants With Clinical Benefit

Time: Up to EOT Follow Up Period (30 [+7] days after the last dose)

Description: Ctrough is the observed serum concentration immediately prior to the next administration.

Measure: Trough Serum Concentration (Ctrough) of Amivantamab

Time: Up to EOT (30 days after last dose)

Description: The AUCtau is the area under the serum concentration-time curve during a dose interval time period (tau)

Measure: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of Amivantamab

Time: Up to EOT (30 days after last dose)

Secondary Outcomes

Description: The Cmax is the maximum observed serum concentration of Amivantamab.

Measure: Maximum Serum Concentration (Cmax) of Amivantamab

Time: Cycle 1 Day 1: predose through end of infusion (EOT) or Follow Up (approximately 16 months) (each cycle is of 28 days)

Description: The Tmax is defined as time to reach maximum observed serum concentration of Amivantamab.

Measure: Time to Reach Maximum Observed Serum Concentration (Tmax) of Amivantamab

Time: Cycle 1 Day 1: predose through EOT or Follow Up (approximately 16 months)

Description: The AUC(t1-t2) is the area under the serum Amivantamab concentration-time curve from time t1 to t2.

Measure: Area Under the Serum Concentration-Time Curve From t1 to t2 Time (AUC[t1-t2]) of Amivantamab

Time: Cycle 1 Day 1: predose through EOT or Follow Up (approximately 16 months)

Description: The AUCtau is the area under the serum concentration-time curve during a dose interval time period (tau)

Measure: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of Amivantamab

Time: Cycle 1 Day 1: predose through EOT or Follow Up (approximately 16 months)

Description: The Ctrough is the observed serum concentration immediately prior to the next administration.

Measure: Trough Serum Concentration (Ctrough) of Amivantamab

Time: Cycle 1 Day 1: predose through EOT or Follow Up (approximately 16 months)

Description: Cmax is the maximum observed serum concentration of lazertinib.

Measure: Maximum Serum Concentration (Cmax) of Lzertinib

Time: Cycle 1 Day 1: predose through EOT (30 [+7] days after last dose [Cycle 4 Day 15]) (each cycle is of 28 days)

Description: Tmax is defined as time to reach maximum observed serum concentration of lazertinib.

Measure: Time to Reach Maximum Observed Serum Concentration (Tmax) of Lazertinib

Time: Cycle 1 Day 1: predose through EOT (30 [+7] days after last dose [Cycle 4 Day 15]) (each cycle is of 28 days)

Description: Ctrough is the observed serum concentration immediately prior to the next administration.

Measure: Trough Serum Concentration (Ctrough) of Lazertinib

Time: Cycle 1 Day 1: predose through EOT (30 [+7] days after last dose [Cycle 4 Day 15]) (each cycle is of 28 days)

Description: The R is the accumulation ratio calculated as Cmax or AUC after multiple doses divided by Cmax or AUC after the first dose, respectively.

Measure: Accumulation ratio (R) of Amivantamab

Time: Cycle 1 Day 1: predose through EOT or Follow Up (approximately 16 months)

Description: Serum levels of antibodies to Amivantamab for evaluation of potential immunogenicity.

Measure: Number of Participants With Anti-Drug Antibodies (ADA)

Time: Cycle 1 Day 1: predose through EOT or Follow Up (approximately 16 months)

Description: PFS is defined as the time from first infusion of study drug to PD or death due to any cause.

Measure: Progression-Free Survival (PFS)

Time: Up to End of Treatment Follow Up Period (30 [+7] days after the last dose)

Description: TTF is defined as the time from the first infusion of the study drug to discontinuation of treatment for any reason, including disease progression, treatment toxicity, death, and will be utilized to capture clinical benefit for patients continuing treatment beyond RECIST v1.1 defined disease progression.

Measure: Time to Treatment Failure (TTF)

Time: Up to End of Treatment Follow Up Period (30 [+7] days after the last dose)

Description: OS is defined as the time from first infusion of study drug to death due to any cause.

Measure: Overall Survival (OS)

Time: Up to End of Treatment Follow Up Period (30 [+7] days after the last dose)

14 A Longitudinal Study Evaluating Molecular Changes Associated With Resistance to First and Third (AZD9291) Generation EGFR TKIs in Patients With EGFR Mutant NSCLC Using "Liquid Biopsy"

Based on the possibilities that both plasma and circulating tumor cells (CTCs) (the "liquid biopsy") may offer, we consider that it could be feasible to longitudinally monitor the genetic evolution and the biologic characteristics of CTCs, by using Circulating tumor DNA (ctDNA) and CTCs as a source of biologic material. This approach could provide information regarding the genetic/molecular changes associated with primary and acquired resistance to AZD9291 and, thus, to facilitate to more appropriately adapt the tailored treatment in this particular group of NSCLC patients. It has been recently reported that the detection of resistant clones, based on the tumor-associated genetic aberrations in the blood, can identify treatment resistance up to 10 months earlier than the radiological methods providing, thus, the potential for an early switch to a non cross-resistant therapy in order to improve patients' outcome.

NCT02771314
Conditions
  1. Non Small Cell Lung Cancer
Interventions
  1. Drug: AZD9291
MeSH:Carcinoma, Non-Small-Cell Lung
HPO:Non-small cell lung carcinoma

The patients will be followed every 3 months for the detection of mutations (T790M), (C797S), (L858R), del 19 EGFR mutations as well as the mutations [(KRAS)/(NRAS), (BRAF), (PI3K)] in the serum/plasma, the determination of the serum levels of Hepatocyte Growth Factor (HGF), the presence of T790M (+) and C797S(+) CTCs as well as the molecular (c-MET) and (HER2 amplification) and phenotypic characterization of CTCs using the filtration platform (ISET). --- T790M --- --- C797S ---

Primary Outcomes

Measure: Biomarkers of resistance to first and third (AZD9291) generation EGFR TKIs, explored by studying baseline serial serum or plasma DNA specimens and baseline Circulating Tumor Cells (CTCs)

Time: Up to 2.5 years

Secondary Outcomes

Measure: Progression free survival (PFS)

Time: Up to 2.5 years

Measure: Overall Survival

Time: Up to 2.5 years

Measure: Response rate, assessed using RECIST 1.1

Time: Up to 2.5 years


HPO Nodes


HP:0002664: Neoplasm
Genes 1522
SF3B1 GFI1B IGF2 FIBP RPS7 WT1 COL7A1 TREX1 HSPG2 CASP8 SLC22A18 MC1R TFE3 KRAS PLAG1 OFD1 BRAF NUMA1 KRT16 PSENEN CTPS1 APC SOX9 FANCM OPCML CDKN2A RPS15A CTNNB1 SDHD EDN3 FCN3 NELFA GJC2 MALT1 HPGD GLI1 CD70 SPINK1 LETM1 PMS1 LRP5 HNF1B EXT1 TCF4 ELMO2 MET ANTXR1 KRT16 KRT10 PAX4 SETBP1 TERT WT1 SMARCB1 GJB6 HRAS STK11 BUB1B GNPTAB MYD88 MCC GJB2 BRCA1 TP63 PDGFRL TARS1 NF1 FGFR3 KARS1 BARD1 BRIP1 GATA2 IL1RN BRAF CD81 TNFRSF13B TYROBP AR LIG4 KLF11 ABL1 MVK BMPR1A PIK3CA B3GALT6 SLC37A4 SOS1 TSC1 FGFR3 ATRX FANCG TET2 KIT SRP72 MPL TP53 SMAD4 EVC2 MAPRE2 DLST BRCA1 DICER1 HRAS AKT1 RNR1 TSC1 TNPO3 XRCC4 DNMT3A NEUROD1 THPO MN1 NOD2 SRSF2 PPM1D FLT4 ATP7A IL7 KRAS GDNF WNT10A EPAS1 COL1A1 IL1B MRAP ADAMTS3 PRKCD SUFU PTCH1 ERCC3 KRT14 CXCR4 HOXD13 IGF2 LIG4 PALB2 BLM NRAS ERCC3 FOXP1 SDHD TP53 PKD2 PDX1 TINF2 ADA2 MYF6 RHBDF2 POU6F2 PHKG2 CDKN2A RUNX1 ERCC2 MAP2K2 WT1 USB1 GATA4 FGFR2 ACD CR2 MUTYH ARL6IP6 FAH MSH2 RASA1 NEK1 SOX6 NR0B1 LIG4 CDKN2B NF1 NF1 POLE RPL35 SRY SDHAF2 FANCL CPLX1 FAS PRKAR1A PHB SDHA CALR PIK3R1 FAN1 TET2 TMEM216 RSPO1 SEMA3D MDM4 SDHD HRAS NUP214 GJA1 PIK3CA CCND1 RNF6 MSH2 C11ORF95 MVK MCM4 FLI1 TINF2 KIAA0753 ECM1 ARSA ERCC2 SOX2 SDHC SLC26A2 MPL VANGL1 PUF60 RAD51D POT1 CR2 ESCO2 FOXE1 PMVK SRY GJB4 TRIM37 KIT EXT2 PDGFB KIF1B FANCF IGF2R MLH1 GDNF PIK3CA ASCC1 ASCL1 TCIRG1 APPL1 RPS19 BCL10 IGF2 NRAS FLT3 STAT1 BCL10 RMRP GNAI3 KRAS GPR101 BAP1 NKX2-1 MAX BMPR1A DDB2 SMARCB1 RAD51 FGFR3 ALX4 BTK MSH6 NOTCH3 DICER1 CXCR4 CCBE1 RET WT1 TP53 PALLD RNASEH2B WT1 ATR CCND1 KCNQ1OT1 SMAD4 AHCY STK11 FANCC TRNK BCL6 SMAD4 SKIV2L HMBS TP53 TERT PHOX2B SNAI2 BRAF TCOF1 FANCI NRAS REST SDHC HBB HFE CREBBP MET SEC23A CEP57 CTLA4 TRIM28 SMAD7 GNAS BRCA2 PALB2 FGF8 SBDS RET ALK GJB2 CPLANE1 GPC3 TCTN3 PTEN RB1 INTU CYP26C1 LEMD3 PRLR CDON NLRP1 GPR101 DHH HNF4A MMEL1 DNASE1L3 RASGRP1 ATRX CHEK2 FANCA SPRED1 DNM2 FLT4 CHEK2 RPS19 KLLN HACE1 HNF1A PTPN11 CDKN1B GAS1 BRCA2 KCNQ1OT1 NPM1 FGFR3 MC1R MINPP1 PTPN11 TSC2 ABCA5 BRCA2 PLCB4 SCN11A HNF1A BRAF RB1 CBL ARHGAP26 SUFU PTPRJ C1S APC IRF5 GNAQ GDNF TERT MYSM1 XPC TMC8 COL4A5 ERBB3 SLC26A4 CD96 NSUN2 PDGFRA FERMT1 TYR DNAJC21 MSH2 SH3GL1 TUBB RET BRAF ESR1 PAX3 RHBDF2 RTL1 WRN DYNC2LI1 ELANE EXOC6B RPS26 EWSR1 VHL PIGA GCGR POU6F2 RNF43 POLE BRAF MNX1 SFTPA2 CDH23 ASCL1 APC ACVR1 PIGL BAX RAG2 RSPO1 MSH3 PGM3 FGF3 FANCE MPL TP53 COL7A1 BUB1 TET2 PALB2 ACTB PNP SDHC EDN3 XPA TMC6 NEK1 GNA11 KAT6B KRT1 RUNX1 PAX7 NOTCH1 ENG CTNNB1 ETV6 MPLKIP PARN CDKN2A PTPN3 STAG3 MDM2 TP53 LAMC2 NBEAL2 VAMP7 GNA14 DCLRE1C CBL GCDH FANCC AXIN2 PYGL SOS1 BLK WRAP53 IDH1 KRAS CCM2 APC ASXL1 ATP7B ERCC3 SF3B1 EP300 BRCA2 MGAT2 NRTN CDKN2A DICER1 PMS1 RPS10 TBC1D24 FAH BRCA2 ASXL1 BCR C2CD3 KRAS IDH1 IGLL1 RASA1 BRCA2 CHEK2 PTCH1 RNF113A BRAF MBTPS2 EDNRB IGHM PDGFRB RAF1 MEN1 FASLG TUBB NDUFAF6 FOXI1 TGFBR1 EPCAM CYLD SDHB APC CYP2D6 TAF1 KRT17 BRCA1 BUB1B BAP1 GDF2 BUB1B ERCC2 TP53 KRT5 GATA2 BRCA1 RAD54B MRE11 STAC3 DNMT3A MLH1 BCHE EDN3 CDKN1B AURKA NRAS FLCN IDH2 EDN1 ESCO2 USF3 IGH POT1 ACVRL1 JAK2 NBN NRAS SQSTM1 TMEM127 ZFPM2 SLC12A3 NTHL1 ADA CHIC2 STAT3 SETBP1 FANCB FIBP STAT3 STK11 MLLT10 SFTPC HDAC4 NUP214 GLI2 SLX4 TSC1 ERCC6 TP53 CLCNKB KLF6 OGG1 JAK2 PAX6 RECQL4 RPL31 MYO1H FH RPGRIP1L SLC45A2 RPL10 RPL10 HMBS GDF5 TNFRSF10B PIK3CA GABRD TP53 BRCA2 SEMA4A BCR PALB2 ASXL1 KRT6B CCDC22 SAMD9 DMPK DCC ERCC5 RPL5 CTNNB1 RPS27 TRNS2 PTCH1 PTEN TFAP2A RPS24 RPL35A RET AXIN1 HNF1B ARMC5 UBE2T SRP54 SSX2 DKC1 ERCC3 JAK2 GNA11 LAMB3 GJB2 NFKB1 KCNQ1 GLI3 PIK3CA KANSL1 CASP8 MYC RECQL4 ACAN CACNA1S BDNF KIF11 MDH2 MSL3 FGFR1 TERF2IP HFE NFKB2 TOP2A GFI1 SRD5A3 PHKA2 MAX POLE MAP2K1 EYA1 RNF43 ALX3 SETD2 ERCC4 CTLA4 SIX3 LEMD3 OCRL CDH23 DZIP1L MSH3 AR CDC73 PDGFRL TWIST1 POU2AF1 DKC1 CALR LIN28B KRT6A GATA1 MC1R DIS3L2 CD28 CDC73 ADA2 UROD CIB1 TSR2 WNT5A TET2 PHOX2B BMPER KIT DLC1 MSTO1 H19-ICR SLC25A13 ADAR TMEM67 BMPR1A MLH3 POLR1C KRT6B FH EFL1 TERC BUB3 FOXC2 NOTCH3 KIT NSD1 FGFR2 SLC6A17 MAP3K1 TRIP13 MEG3 RRAS2 BMPR1A NF1 DPM1 LIG4 PARN RHOH BRCA2 NF1 TAF15 RFWD3 VHL H19 BCR KRAS VANGL2 KRAS SDHD DVL3 BIN1 ABL1 GPC3 HAX1 FANCA GDNF NHP2 IGF2 VHL CCL2 EXTL3 RUNX1 PRKCD BLNK MSH6 SLC22A18 IL2RG PTH1R SDHB AIP WDPCP APC KCNJ10 ASPSCR1 OCA2 TP53 WT1 SPRTN TET2 TAL1 L2HGDH KIT SDHC ERCC4 GPR143 PRKN SMAD4 SEMA3C TRNS1 BRCA1 SHOX PCNA FANCG CREB1 TRNH VHL MYLK BAP1 SUFU ANTXR1 POLD1 NODAL IGH JAK2 MS4A1 MEN1 TSC2 GATA2 DHCR7 TINF2 F13B RB1 COL7A1 SCN4A BMPR1A DDB2 CDKN2A SDHD CYP11B2 IL7 ARID1B KIT FGFR1 RET CDKN2A LAMA3 CHEK2 TBX2 TBX18 HNF4A GPC4 SHH LMNA BMP2 YY1 AKT1 WT1 BAP1 FZD2 SH2B3 BTK GATA1 RAD54L ATM CTBP1 PTEN SRY RYR1 CTHRC1 MFN2 PTEN RAD21 PTEN MYC SLC26A2 TP53 CTNNB1 RAD51C NAB2 NLRP1 SUFU DLL1 PSAP SDHB REST TGFBR2 TRIP13 IGH ABCC8 IL6 CPLANE1 H19 FANCD2 FGFR2 RET PKD1 DNMT3A REST CHEK2 GNAQ MXI1 BRIP1 DYNC2LI1 GNAS TP53 GLI3 DIS3L2 NRAS PICALM WT1 BAP1 MEN1 TXNRD2 MGMT PTEN MYD88 GNAS POT1 AGGF1 BUB1 PTEN PORCN HFE NUTM1 PHOX2B MSX2 PMS2 SLX4 H19 USP9X RPL27 GNAS SEC23B CBL CD28 PKHD1 AXIN2 TRPV3 KLLN SSX1 TSC1 PPOX KRT17 CARD14 HRAS TCF3 RPL11 CC2D2A GREM1 CHEK2 AP2S1 NRAS TRNL1 ALX1 CREBBP TCTN3 TET2 ESCO2 DOCK8 NRAS STK11 GCM2 TTC37 WT1 SMAD4 DAXX MITF BCL2 DIS3L2 POLR1D TDGF1 KRAS TNFRSF13C KIT PHOX2B SF3B1 RPL15 NF1 TERT TNFRSF1B FANCD2 MLH3 IL7R GPC4 H19-ICR SLC17A9 MEN1 MST1R KIT RAD50 TJP2 DNAJC21 PDCD10 MUTYH IL12RB1 SH2D1A FGFR2 NBN KRAS KIT CASR ENPP1 SDHB HRAS IKBKG PNP EXT2 BRD4 SMARCB1 REST COL11A2 TG KIT LIG4 SUFU NBN RSPRY1 CYSLTR2 SDHD AAGAB BLM RAG1 RNF139 RB1CC1 ACD PTPN11 SLC26A2 TREX1 BMPR1B DDR2 ZAP70 MNX1 MAGT1 AIP GATA2 AR STAR IFIH1 IDH2 BRCA1 USP8 RB1 FGFRL1 SMO USP8 RMRP SLC25A11 MLH3 FUZ DOCK8 SUFU NF2 KDR KRAS RPS14 CASP10 SRP54 ZSWIM6 TBXT PTCH2 EWSR1 TNFRSF13C MTAP NQO2 RPL18 DNAJC21 GCK ERCC6 KDM6B EXT1 SBDS CCND1 SDHAF2 KCNH1 CYLD LMOD1 PDGFRA CAT CHRNG TRNQ ADA NRAS TLR2 SHOX FGFR3 BCL10 TYR KRAS COL2A1 PTCH2 SMO GBA MSTO1 TREM2 JAK2 TMEM231 MSH2 ASXL1 RET DHCR7 NBN PIK3CA NSD2 SDHB EIF2AK4 PALB2 KIF7 PTPN11 PIK3CA HLA-DRB1 STIM1 TMC6 KIF1B TNFSF15 RELA AKT1 NPM1 APC SDHA SDHB STAT6 CDKN1C CDC73 PTCH2 KANSL1 ZSWIM6 FLCN HBB LZTS1 FN1 TRAF7 ACP5 CTNNB1 MLH1 EXT2 RNASEL RNASEH2A IL2RG ATP7A CDK4 CYP11B1 MMP1 SDHB ATRX ACTG2 FOXH1 OFD1 NEK9 STS MUC5B PRKCD PTPN11 PTCH2 LRRC8A RPL26 MSH6 NNT LZTR1 CDC73 PTEN AKT1 AKT1 SASH1 HRAS ANAPC1 PTPN12 KCNJ11 TCF4 GATA2 MLH3 ERCC4 GNB1 DISP1 IDH1 BCR GANAB MSH6 NR5A1 TSC2 GFI1 TNFSF12 TRNP MAPK1 IFNG FLT4 MTM1 WWOX HABP2 RPS28 HRAS SLCO2A1 ND5 SDHB CHD7 BRIP1 SLC37A4 MC2R XRCC3 TNFRSF4 NAGS PHF21A ZIC2 PCGF2 SMARCE1 CTNNB1 SRP54 CDH1 CDK4 RPS20 KCNJ10 RAD21 RNF6 COL14A1 SMO CD19 WRN SRGAP1 CDKN2C AXIN2 GPC6 WWOX HSPA9 FOXI1 CPOX RPS17 APC2 MYH8 SERPINA1 ATM LMX1B ENG POLH TGFBR2 DHX37 VEGFC KIF1B KRT17 DDX41 SPIB CBFB HRAS BCL10 PIGL FGFR1 NSD1 F5 KCNN3 BAX PIEZO2 RECQL4 CREBBP KIT PDGFB PDE6D ABCA5 AKT1 KLHDC8B TNFSF12 EPCAM RARA MLH1 GINS1 EVC PIK3CA FANCE WIPF1 NF2 PDGFRA PRKAR1A CDH1 SDHD PRCC TRNF PTCH1 TNFRSF1B WNT10A WWOX MAD1L1 MTOR WDPCP RNASEH2C NSD2 SAMD9L FH LPP NF1 KRIT1 NTHL1 IL12A HNF1A CDH1 SMARCB1 SMARCE1 CD19 FH FDPS TRPS1 ERCC4 SMPD1 SMARCD2 BRCA1 MPL CRKL SEC23A EXT1 PERP ATM FOXE1 CDKN2B CTSC SIX1 FAM149B1 CDH1 RAD51C ALX3 DLST TRIP13 ING1 PDGFRB FLT3 COL18A1 MST1 TGIF1 TMEM107 SRSF2 TRIM28 BAP1 ANTXR2 CD79A PIK3R1 MAP3K1 NOP10 PIK3CA POLD1 KDSR CCND1 TP53 TMC8 ALK MAP2K1 CD79B SDHC ECE1 PALLD CTSA PRDM16 IVNS1ABP CALR FLNA GPR101 BRCA2 ERCC2 DYNC2H1 TFAP2A COL2A1 DVL1 TERT APC TERT TEK EXT2 TERC ALX4 OFD1 LMO1 PDGFRB RPS14 DCC RTEL1 INS TSC2 FAM20C MYH11 GPC3 SCN9A SMAD4 RASGRP1 HBB TGFBR2 RERE NDP PLA2G2A TCF4 MAD2L2 SKI AIP HMMR SDHC SNAI2 PIK3CA LMNA PGM3 ABCB11 TAL2 WT1 VHL PIK3CA TCTN3 SAMD9L ICOS GLI3 RB1 SLC25A13 SDHC DCLRE1C GCM2 VANGL1 SIX6 WT1 PMS2 KCNH1 BARD1 H19-ICR GNAS TERT CIB1 B3GALT6 GJB3 ERBB2 SDHA KRAS CDC73 TNFRSF13B TET2 FGFR3 WAS SEC23B TGFBR2 TP53 NF2 SMARCA4 NF2 SLC26A4 ANTXR2 WRAP53 FAS SAMHD1 TP53 TET2 ATP7A PTEN SH3KBP1 CARMIL2 MVD PDGFB ABCC6 G6PC1 TRNK KRAS GPC3 PTEN NF2 JAK2 DMRT3 GNAQ RAD51 GTF2H5 TMEM127 TERT RUNX1 FAT4 AR HABP2 NR4A3 EP300 MINPP1 OFD1 RASA1 DLEC1 BIRC3 AIP CD27 PHOX2B BMPR1A KCNE3 PLCD1 RAD51 KRT1 MSH3 MITF EPHB2 DHCR24 RABL3 KRT17 XRCC2 NRAS ITK VHL BICC1 RECQL4 SMARCAD1 MYCN RET CTC1 PTCH1 JAK2 SRC SDHB PHOX2B AKT1 KEAP1 JAG1 VHL LETM1 NLRP1 MEN1 BRCA2 FLCN C2CD3 RFWD3 XPA APC APC SDHD FOXO1 MAFA WHCR GPC4 MLH1 ICOS CDKN1B MTMR14 KIT DICER1 EP300 ZFHX3 MMP1 PRKAR1A KRT9 F13A1 CTNNB1 MPL INPP5E NF1 DKC1 TERT DLK1 SCN10A STS RPS29 PTEN FLCN LRBA ELANE GTF2E2 ATM PIK3CA GPR35 CYLD RAD51C CDKN1A WT1 DICER1 PIK3CA TERC PIK3CA SLC25A11 GNAS CEBPA ATP6V1B2 RET XPC EXT1 BRCA2 SH2B3 ERCC3 BRCA2 RTEL1 WASHC5 ERCC2 AKT1 KCNAB2 CYLD STK4 POLH ERCC5 CDH1 CEL XIAP MSR1 TP53 TET2 DHH PRKAR1A