Gene Variant Detail

Gene EGFR
Variant T790M
Impact List missense
Protein Effect gain of function
Gene Variant Descriptions EGFR T790M is a gatekeeper mutation that lies within the ATP-binding pocket of the Egfr protein (PMID: 20026433). T790M results in increased Egfr kinase activity and is a frequently occurring secondary somatic mutation that results in resistance to reversible tyrosine kinase inhibitors (PMID: 18227510, PMID: 20026433).

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Transcript NM_005228
gDNA chr7:g.55181378C>T
cDNA c.2369C>T
Protein p.T790M
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
NM_005228 chr7:g.55181378C>T c.2369C>T p.T790M RefSeq GRCh38/hg38

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
EGFR exon 19 del EGFR T790M KRAS amp non-small cell lung carcinoma sensitive Osimertinib + Selumetinib Preclinical Actionable In a preclinical study, the combination of Tagrisso (osimertinib) and Selumetinib increased Parp cleavage, and highly suppressed phosphorylated Erk in human non-small cell lung cancer cells harboring EGFR exon 19 deletion, EGFR T790M, and a gain in KRAS in culture (PMID: 25870145). 25870145
EGFR exon 19 del EGFR T790M KRAS amp non-small cell lung carcinoma resistant Gefitinib Preclinical Actionable In a preclinical study, non-small cell lung cancer cells harboring EGFR exon 19 deletion became resistant to Iressa (gefitinib) after the emergence of EGFR T790M and amplified KRAS in culture (PMID: 25870145). 25870145
EGFR exon 19 del EGFR T790M KRAS amp non-small cell lung carcinoma resistant Osimertinib Preclinical Actionable In a preclinical study, non-small cell lung cancer cells harboring EGFR exon 19 deletion, EGFR T790M and amplified KRAS were resistant to Tagrisso (osimertinib) treatment in culture (PMID: 25870145). 25870145
EGFR L858R EGFR L718Q EGFR T790M Advanced Solid Tumor resistant CO1686 Preclinical Actionable In a preclinical study, transformed cells expressing an EGFR L858R/EGFR T790M/EGFR L718Q triple mutation demonstrated resistance to Rociletinib (CO-1686) in culture (PMID: 25948633). 25948633
EGFR L858R EGFR L718Q EGFR T790M Advanced Solid Tumor resistant Osimertinib Preclinical Actionable In a preclinical study, transformed cells expressing an EGFR L858R/EGFR T790M/EGFR L718Q triple mutation demonstrated resistance to AZD9291 in culture (PMID: 25948633). 25948633
EGFR C797S EGFR D770_N771insNPG EGFR T790M Advanced Solid Tumor predicted - resistant OBX1-012 Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EGFR C797S, EGFR D770_N771insNPG, and EGFR T790M did not respond to treatment with OBX1-012 in culture (PMID: 29754184). 29754184
EGFR C797S + EGFR L747_P753delinsS + EGFR T790M Advanced Solid Tumor resistant Nazartinib Preclinical - Cell culture Actionable In a preclinical study, overexpression of EGFR C797S in addition to EGFR L747_P753delinsS and T790M conferred resistance to Nazartinib (EGF816) in transformed cells in culture (PMID: 29285266). 29285266
EGFR C797S + EGFR L747_P753delinsS + EGFR T790M Advanced Solid Tumor resistant Erlotinib Preclinical - Cell culture Actionable In a preclinical study, overexpression of EGFR C797S in addition to EGFR L747_P753delinsS and T790M conferred resistance to Tarceva (erlotinib) in transformed cells in culture (PMID: 29285266). 29285266
EGFR C797S + EGFR L747_P753delinsS + EGFR T790M Advanced Solid Tumor resistant Afatinib Preclinical - Cell culture Actionable In a preclinical study, overexpression of EGFR C797S in addition to EGFR L747_P753delinsS and T790M conferred resistance to Gilotrif (afatinib) in transformed cells in culture (PMID: 29285266). 29285266
EGFR C797S + EGFR L747_P753delinsS + EGFR T790M Advanced Solid Tumor resistant Osimertinib Preclinical - Cell culture Actionable In a preclinical study, overexpression of EGFR C797S in addition to EGFR L747_P753delinsS and T790M conferred resistance to Tagrisso (osimertinib) in transformed cells in culture (PMID: 29285266). 29285266
EGFR C797S + EGFR L747_P753delinsS + EGFR T790M Advanced Solid Tumor resistant Naquotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing a combination of EGFR C797S, EGFR L747_P753delinsS, and EGFR T790M were resistant to Naquotinib (ASP8273) in culture (PMID: 29467275). 29467275
EGFR L858R EGFR T790M MET amp MET D1231Y lung adenocarcinoma predicted - resistant Cabozantinib + Osimertinib Clinical Study Actionable In a clinical case study, a patient with lung adenocarcinoma harboring EGFR L858R, EGFR T790M, MET amplification, MET D1228H, MET D1228N, MET Y1230H, and MET D1231Y demonstrated initial symptomatic improvement and lung nodule shrinkage following treatment Cometriq (Cabometyx, cabozantinib) and Tagrisso (osimertinib) in combination, but progressed after 1 month and was found to have lost MET D1228H, MET D1228N, and MET Y1230H, and to have an increased allele fraction of MET D1231Y (PMID: 29128427). 29128427
EGFR T790M non-small cell lung carcinoma sensitive Selumetinib + BEZ235 Preclinical - Cell line xenograft Actionable In a preclinical study, Selumetinib (AZD6244) in combination with BEZ235, synergistically inhibited proliferation of Iressa (gefitinib)-resistant NSCLC cells harboring EGFR T790M in culture and in cell line xenograft models (PMID: 24939055). 24939055
EGFR T790M non-small cell lung carcinoma sensitive Amlexanox + Selumetinib Preclinical - Cell line xenograft Actionable In a preclinical study, non-small cell lung cancer cell lines harboring activating EGFR mutations, including EGFR T790M, demonstrated sensitivity to the combination of amlexanox and Selumetinib (AZD6244), resulting in synergistic growth inhibition in culture and reduced tumor growth in xenograft models (PMID: 27287717). 27287717
EGFR T790M non-small cell lung carcinoma sensitive Avitinib maleate Phase I Actionable In a Phase I trial, Avitinib maleate (AC0010) treatment resulted in decreased EGFR T790M allele frequency in cell free DNA of non-small cell lung carcinoma patients with acquired resistance to first generation Egfr tyrosine kinase inhibitor, and resulted in partial response or stable disease (PMID: 29626621). 29626621
EGFR T790M non-small cell lung carcinoma sensitive Avitinib maleate Clinical Study Actionable In a clinical study, two patients with non-small cell lung cancer harboring EGFR T790M demonstrated tumor reductions of 31% and 36% when treated with Avitinib maleate (AC0010) (PMID: 27573423). 27573423
EGFR T790M lung cancer sensitive CUDC-101 Preclinical Actionable In a preclinical study, CUDC-101 inhibited the growth of lung cancer cells expressing EGFR T790M (PMID: 20388807). 20388807
EGFR T790M non-small cell lung carcinoma sensitive BEZ235 Preclinical Actionable In a preclinical study, BEZ235 suppressed the growth of an Iressa (gefitinib)-resistant NSCLC cell line with an EGFR T790M mutation (PMID: 24939055). 24939055
EGFR T790M non-small cell lung carcinoma decreased response Icotinib Clinical Study Actionable In a retrospective analysis, non-small cell lung cancer patients harboring EGFR T790M demonstrated a response rate of 4.76% and disease control rate of 47.62%, and a median progression-free survival of 1.6 months following treatment with icotinib (J Clin Oncol 35, 2017 (suppl; abstr e14050)). detail...
EGFR T790M non-small cell lung carcinoma sensitive Naquotinib Phase I Actionable In a Phase I trial, ASP8273 treatment resulted in partial response in 38% (15/40) and stable disease in 28% (11/40) of non-small cell lung carcinoma patients harboring EGFR T790M, with a median progression free survival of 6.7 months (J Clin Oncol 34, 2016 (suppl; abstr 9050)). detail...
EGFR T790M non-small cell lung carcinoma sensitive Nazartinib Phase I Actionable In a Phase I study, EGF816 treatment resulted in an objective response rate of 44% (56/127), disease control rate of 91% (115/127), and an estimated progression-free survival of 9.2 months in non-small cell lung carcinoma patients harboring EGFR T790M (J Clin Oncol 34, 2016 (suppl; abstr 9044); NCT02108964). detail...
EGFR T790M lung adenocarcinoma resistant Gefitinib Clinical Study Actionable In a clinical study, EGFR T790M mutations were associated with resistance to Iressa (gefitinib) in lung adenocarcinoma patients (PMID: 15737014). 24410791 15737014
EGFR T790M Advanced Solid Tumor sensitive AV-412 Preclinical Actionable In a preclinical study, AV-412 inhibited the kinase activity of EGFR T790M (PMID: 17888033). 17888033
EGFR T790M non-small cell lung carcinoma sensitive Osimertinib Guideline Actionable Tagrisso (osimertinib) is included in guidelines as subsequent therapy in patients with EGFR T790M-positive, metastatic non-small cell lung cancer who have progressed on Tarceva (erlotinib), Iressa (gefitinib), or Gilotrif (afatinib), and in patients who have progression with symptomatic brain metastases (NCCN.org). detail...
EGFR T790M non-small cell lung carcinoma sensitive Osimertinib FDA approved Actionable In a Phase I extension trial that supported FDA approval, treatment with Tagrisso (osimertinib) resulted in in an objective response rate of 58% (115/119) and disease control rate of 92% in patients with EGFR-TKI resistant non-small cell lung cancer harboring EGFR T790M mutations (World Conf on Lung Cancer 2015. Abst MINI16.06). detail...
EGFR T790M non-small cell lung carcinoma sensitive Osimertinib Phase I Actionable In a Phase I trial, AZD9291 treatment resulted in an objective response rate of 61% (78/127) and a disease control rate of 95% (121/127) in NSCLC patients harboring EGFR T790M mutations (PMID: 25923549). 25923549
EGFR T790M non-small cell lung carcinoma sensitive Osimertinib Phase III Actionable In a Phase III trial (AURA3), treatment with Tagrisso (osimertinib) resulted in an improved median progression-free survival of 10.1 months vs. 4.4 months with platinum plus pemetrexed, and an objective response rate of 71% (95% CI, 65 to 76) compared to 31% (95% CI, 24 to 40) with platinum plus pemetrexed therapy in patients with EGFR T790M-positive non-small cell lung cancer (PMID: 27959700; NCT02151981). 27959700
EGFR T790M non-small cell lung carcinoma sensitive Osimertinib Phase II Actionable In Phase II clinical trials (AURA extension and AURA2), Tagrisso (osimertinib) treatment resulted in a central nervous system (CNS) overall response rate of 54% (24/50), including 6 complete responses, and a CNS disease control rate of 92% (46/50) in non-small cell lung cancer patients with CNS metatstases harboring EGFR T790M (PMID: 29293889; NCT01802632, NCT02094261). 29293889
EGFR T790M non-small cell lung carcinoma sensitive Osimertinib Phase I Actionable In a Phase I trial, AZD9291 demonstrated efficacy in 50% (9/18) of NSCLC patients carrying EGFR T790M mutations (PMID: 24410791). 24410791
EGFR T790M non-small cell lung carcinoma resistant Erlotinib Clinical Study Actionable In a clinical study, 83% (5/6) of non-small cell lung cancer patients that had progressed on prior treatment with Iressa (gefinitib) with secondary EGFR T790M mutations had progressive disease as best response to treatment with Tarceva (erlotinib) (PMID: 18981003). 18981003 24410791
EGFR T790M non-small cell lung carcinoma sensitive CO1686 Phase Ib/II Actionable In a Phase Ib/II trial, treatment with Rociletinib (CO-1686) resulted in a response rate of 59% (27/46) and a disease control rate of 93% (43/46) in non-small cell lung cancer patients harboring EGFR T790M (PMID: 25923550). 25923550
EGFR T790M non-small cell lung carcinoma sensitive CO1686 Phase I Actionable In a Phase I trial, CO-1686 has demonstrated safety and efficacy in NSCLC patients carrying EGFR T790M mutations (J Clin Oncol 31, 2013 (suppl; abstr 2524)). detail...
EGFR T790M non-small cell lung carcinoma no benefit Brigatinib Phase Ib/II Actionable In a Phase I/II trial, Alunbrig (brigatinib) treatment did not result in objective response in EGFRT790M-positive non-small cell lung cancer patients resistant to one previous EGFR tyrosine kinase inhibitor (PMID: 27836716). 27836716
EGFR T790M non-small cell lung carcinoma sensitive HM61713 Phase II Actionable In a Phase II trial, BI 1482694 (HM61713) treatment resulted in a disease control rate of 90% (64/71), and objective response with a median duration of 8.3 months in 56% (40/71) of patients with EGFR tyrosine kinase inhibitor-resistant non-small cell lung carcinoma harboring EGFR T790M (J Clin Oncol 34, 2016 (suppl; abstr 9055)). detail...
EGFR T790M non-small cell lung carcinoma predicted - sensitive Epitinib Phase I Actionable In a Phase I clinical trial, HMPL-813 (Epitinib) demonstrated safety and preliminary efficacy in patients with NSCLC, including a patient with EGFR T790M (J Clin Oncol 31, 2013 (suppl; abstr e19042). detail...
EGFR T790M non-small cell lung carcinoma predicted - sensitive Alflutinib Phase I Actionable In a Phase I trial, Alflutinib (AST2818) treatment resulted in an objective response rate of 58.3% (7/12) and a disease control rate of 91.7% (11/12) in patents with non-small cell lung cancer harboring EGFR T790M whose disease progressed on EGFR tyrosine kinase inhibitor therapy (J Thorac Oncol. Nov 2017, Vol 12, Issue 11, Suppl. 2, pS2138). detail...
EGFR T790M non-small cell lung carcinoma decreased response Selumetinib Preclinical Actionable In a preclinical study, Selumetinib (AZD6244) mildly inhibited the growth of an Iressa (gefitinib)-resistant NSCLC cell line with an EGFR T790M mutation (PMID: 24939055). 24939055
EGFR T790M non-small cell lung carcinoma predicted - resistant Afatinib Clinical Study Actionable In a prospective clinical study, Gilotrif (afatinib) treatment resulted in partial response in 15% (4/27), stable disease in 56% (15/27), and progressive disease in 30% (8/27) of non-small cell lung carcinoma patients carrying an EGFR T790M mutation (PMID: 26354527). 26354527
EGFR T790M non-small cell lung carcinoma predicted - resistant Afatinib Phase II Actionable In a post-hoc analysis of Phase II and Phase III trials (LUX-Lung2, LUX-Lung 3, LUX-Lung 6), Gilotrif (afatinib) treatment resulted in an objective response rate of 14.3% (2/14) in non-small cell lung cancer patients harboring EGFR T790M, with a mean progression-free survival of 2.9 months, and an overall survival of 14.9 months (PMID: 26051236; NCT00525148, NCT00949650, and NCT01121393). 26051236
EGFR T790M lung adenocarcinoma resistant Afatinib Clinical Study Actionable In a clinical study, second-site EGFR T790M mutations were detected in 47.6% (20/42) of lung adenocarcinoma patients with acquired resistance to Gilotrif (afatinib) (PMID: 26862733). 26862733
EGFR E746_A750del EGFR T790M EGFR L844V non-small cell lung carcinoma resistant CO1686 Preclinical Actionable In a preclinical study, expression of an EGFR E746_A750del/EGFR T790M/EGFR L844V triple mutation conferred resistance to Rociletinib (CO-1686) in non-small cell lung cancer cells harboring EGFR E746_A750del and EGFR T790M in culture (PMID: 25948633). 25948633
EGFR E746_A750del EGFR T790M EGFR L844V non-small cell lung carcinoma sensitive Osimertinib Preclinical Actionable In a preclinical study, AZD9291 inhibited growth of non-small cell lung cancer cells harboring EGFR E746_A750del and EGFR T790M and ectopically expressing an EGFR E746_A750del/EGFR T790M/EGFR L844V triple mutation in culture (PMID: 25948633). 25948633
EGFR E746_A750del EGFR T790M EGFR L844V Advanced Solid Tumor sensitive Osimertinib Preclinical Actionable In a preclinical study, AZD9291 inhibited growth of transformed cells expressing an EGFR E746_A750del/EGFR T790M/EGFR L844V triple mutation in culture (PMID: 25948633). 25948633
EGFR E746_A750del EGFR T790M EGFR L844V Advanced Solid Tumor resistant CO1686 Preclinical Actionable In a preclinical study, transformed cells expressing an EGFR E746_A750del/EGFR T790M/EGFR L844V triple mutation demonstrated resistance to Rociletinib (CO-1686) in culture (PMID: 25948633). 25948633
EGFR G719A EGFR T790M Advanced Solid Tumor resistant Afatinib Preclinical - Cell culture Actionable In a preclinical study, acquisition of EGFR T790M was associated with resistance to Gilotrif (afatinib) in transformed cells expressing EGFR G719A in culture (PMID: 27913578). 27913578
EGFR L858R EGFR T790M lung adenocarcinoma sensitive Afatinib + Cetuximab + Sirolimus Preclinical Actionable In a preclinical study, addition of Rapamune (sirolimus) to Gilotrif (afatinib) and Erbitux (cetuximab) combination treatment restored sensitivity in transgenic animal models of lung adenocarcinoma driven by EGFR L858R and T790M that acquired resistance to the combination treatment, resulted in tumor shrinkage (PMID: 24813888). 24813888
EGFR L858R EGFR T790M lung adenocarcinoma resistant Erlotinib Preclinical Actionable In a preclinical study, EGFR T790M was detected in animal models of EGFR L858R-induced lung adenocarcinoma, which occurred after repeated treatments with Tarceva (erlotinib) and resulted in drug resistance (PMID: 26341921). 26341921
EGFR L858R EGFR T790M lung cancer sensitive Dasatinib + Osimertinib Preclinical - Cell culture Actionable In a preclinical study, the addition of Sprycel (dasatinib) to treatment with Tagrisso (osimertinib) resulted in increased PARP cleavage and inhibition of proliferation in lung cancer cell lines harboring EGFR L858R and T790M in culture (PMID: 28416483). 28416483
EGFR L858R EGFR T790M Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited growth of transformed cells expressing EGFR L858R and T790M in culture (PMID: 27780853). 27780853
EGFR L858R EGFR T790M non-small cell lung carcinoma resistant Lapatinib Preclinical Actionable In a preclinical study, non-small cell carcinoma cancer cell lines harboring EGFR L858R and T790M mutations demonstrated resistance to growth inhibition by Tykerb (lapatinib) in culture (PMID: 18199554). 18199554
EGFR L858R EGFR T790M non-small cell lung carcinoma sensitive CO1686 Phase Ib/II Actionable In a Phase Ib/II trial, treatment with Rociletinib (CO-1686) resulted in an objective response rate of 53.3% (8/15) in non-small cell lung cancer patients harboring both EGFR L858R and EGFR T790M (PMID: 25923550). 25923550
EGFR L858R EGFR T790M non-small cell lung carcinoma sensitive CO1686 Preclinical - Pdx Actionable In a preclinical study, Rociletinib (CO-1686) inhibited tumor growth in human non-small cell lung cancer cell line and patient-derived xenograft models of non-small cell lung cancer harboring both EGFR L858R and EGFR T790M (PMID: 24065731). 24065731
EGFR L858R EGFR T790M Advanced Solid Tumor resistant Erlotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing both EGFR L858R and EGFR T790M were resistant to Tarceva (erlotinib) in culture (PMID: 29467275). 29467275
EGFR L858R EGFR T790M non-small cell lung carcinoma sensitive Naquotinib Preclinical - Cell culture Actionable In a preclinical study, Naquotinib (ASP8273) inhibited EGFR signaling and proliferation of non-small cell lung cancer cells harboring both EGFR L858R and EGFR T790M in culture (PMID: 29467275). 29467275
EGFR L858R EGFR T790M non-small cell lung carcinoma sensitive Gedatolisib + Neratinib Preclinical Actionable In a preclinical study, Gedatolisib (PKI-587) and Nerlynx (neratinib) in combination worked syngerstically to inhibit Akt phosphorylation in a human non-small cell lung cancer cell line harboring EGFR L858R and T790M in culture (PMID: 21325073). 21325073
EGFR L858R EGFR T790M non-small cell lung carcinoma resistant Erlotinib Preclinical - Cell culture Actionable In a preclinical study, non-small cell lung cancer cells harboring both EGFR L858R and EGFR T790M were resistant to Tarceva (erlotinib) in culture (PMID: 29467275). 29467275
EGFR L858R EGFR T790M non-small cell lung carcinoma resistant Gefitinib Clinical Study Actionable In a clinical case report, a non-small cell lung cancer patient that progressed on Iressa (gefitinib) was demonstrated to harbor EGFR L858R and a secondary EGFR T790M mutation (PMID: 15737014). 15737014
EGFR L858R EGFR T790M non-small cell lung carcinoma resistant Gefitinib Clinical Study Actionable In a clinical study, EGFR T790M mutations were associated with acquired resistance to Iressa (gefitinib) in non-small cell lung cancer patients harboring EGFR L858R (PMID: 22263058). 22263058
EGFR L858R EGFR T790M non-small cell lung carcinoma predicted - sensitive Osimertinib + Ramucirumab Phase I Actionable In a Phase I trial, Cyramza (ramucirumab) and Tagrisso (osimertinib) combination treatment resulted in an objective response rate of 76% (19/25, 1 complete response, 18 partial response), and stable disease in 16% (4/25) of EGFR-mutant (exon 19 deletion or L858R) non-small cell lung cancer patients harboring EGFR T790M, who progressed on first-line EGFR TKI therapy (J Clin Oncol 36, 2018 (suppl; abstr 9053); NCT02789345). detail...
EGFR L858R EGFR T790M Advanced Solid Tumor sensitive Cetuximab + EAI045 Preclinical - Cell culture Actionable In a preclinical study, EAI045 and Erbitux (cetuximab) synergistically inhibited proliferation of transformed cells over expressing EGFR that harbors both L858R and T790M in culture (PMID: 27251290). 27251290
EGFR L858R EGFR T790M non-small cell lung carcinoma no benefit EAI045 Preclinical - Cell culture Actionable In a preclinical study, EAI045 inhibited Egfr activation but not proliferation of non-small cell lung cancer cells harboring EGFR with both L858R and T790M mutations in culture (PMID: 27251290). 27251290
EGFR L858R EGFR T790M lung adenocarcinoma sensitive JNJ-61186372 Preclinical - Pdx Actionable In a preclinical study, JNJ-61186372 induced tumor regression in lung adenocaricnoma patient-derived xenograft (PDX) models harboring EGFR L858R and EGFR T790M, with response continuing up to 2 months post-treatment cessation (PMID: 27216193). 27216193
EGFR L858R EGFR T790M lung adenocarcinoma resistant Afatinib + Cetuximab Preclinical Actionable In a preclinical study, EGFR T790M was detected in animal models of EGFR L858R-induced lung adenocarcinoma, which developed after repeated Gilotrif (afatinib) and Erbitux (cetuximab) combination treatments and resulted in drug resistance (PMID: 26341921). 26341921
EGFR L858R EGFR T790M non-small cell lung carcinoma sensitive Osimertinib Phase I Actionable In a Phase I trial, AZD9291 treatment resulted in a response rate of 57% (24/24) in patients harboring both EGFR L858R and T790M mutations (PMID: 25923549). 25923549
EGFR L858R EGFR T790M non-small cell lung carcinoma sensitive Osimertinib Clinical Study Actionable In a clinical case study, Tagrisso (osimertinib) resulted in a partial response and stable disease of brain metastases in a NSCLC patient harboring EGFR L858R and a secondary resistance mutation, EGFR T790M, which occurred post Tarceva (erlotinib) therapy (PMID: 27435396). 27435396
EGFR L858R EGFR T790M non-small cell lung carcinoma sensitive Osimertinib Phase III Actionable In a Phase III trial, third-line treatment with Tagrisso (osimertinib) resulted in improved median progression-free survival compared to treatment with the combination of Taxotere (docetaxel) and Avastin (bevacizumab) (10.2 mo vs. 2.95 mo., HR=0.23), and a an overall response rate of 61.6% (45/73) compared to 8.3% (6/72), in patients with non-squamous non-small cell lung cancer harboring EGFR T790M with either EGFR L858R or an EGFR exon 19 deletion (PMID: 29858027, NCT02959749). 29858027
EGFR L858R EGFR T790M lung adenocarcinoma sensitive Osimertinib + Selumetinib Preclinical Actionable In a preclinical study, the combination of Tagrisso (osimertinib) and Selumetinib inhibited growth of lung adenocarcinoma tumors driven by EGFR L858R and EGFR T790M that had developed resistance through continued exposure to Tagrisso (osimertinib) (PMID: 25870145). 25870145
EGFR L858R EGFR T790M lung cancer sensitive BKM120 + Osimertinib Preclinical - Cell culture Actionable In a preclinical study, the addition of Buparlisib (BKM-120) to treatment with Tagrisso (osimertinib) resulted in increased inhibition of proliferation in lung cancer cell lines harboring EGFR L858R and T790M in culture (PMID: 28416483). 28416483
EGFR L858R EGFR T790M non-small cell lung carcinoma sensitive Ibrutinib Preclinical - Cell line xenograft Actionable In a preclinical study, Imbruvica (ibrutinib) inhibited Egfr activity and down stream signaling, resulting in cell cycle arrest in culture and delayed tumor progression in cell line xenograft models of non-small cell lung cancer harboring both EGFR L858R and T790M (PMID: 26375053). 26375053
EGFR L858R EGFR T790M non-small cell lung carcinoma sensitive Afatinib Preclinical - Cell culture Actionable In a preclinical study, Gilotrif (afatinib) inhibited EGFR signaling and proliferation of non-small cell lung cancer cells harboring both EGFR L858R and EGFR T790M in culture (PMID: 29467275). 29467275
EGFR L858R EGFR T790M non-small cell lung carcinoma sensitive Erlotinib + Ganetespib Preclinical - Cell line xenograft Actionable In a preclinical study, the addition of Ganetespib overcame resistance to Tarceva (erlotinib) in cell line xenograft models of non-small cell lung cancer harboring EGFR L858R and EGFR T790M (PMID: 25077897). 25077897
EGFR L858R EGFR T790M lung cancer predicted - sensitive TAS6417 Preclinical - Cell culture Actionable In a preclinical study, TAS6417 inhibited growth of a lung cancer cell line harboring EGFR L858R and EGFR T790M in culture (PMID: 29748209). 29748209
EGFR L858R EGFR T790M non-small cell lung carcinoma sensitive TAE226 Preclinical Actionable In a preclinical study, TAE226 treatment inhibited proliferation of non-small cell lung carcinoma cell lines harboring both EGFR L858R and EGFR T790M mutations in culture (PMID: 26090892). 26090892
EGFR L858R EGFR T790M Advanced Solid Tumor decreased response EKI-285 Preclinical Actionable In a preclinical study, transformed cells expressing EGFR L858R and T790M demonstrated decreased sensitivity to EKI-285 (CL-387,785) in culture (PMID: 17085664). 17085664
EGFR L858R EGFR T790M lung cancer sensitive Osimertinib + Selumetinib Preclinical - Cell culture Actionable In a preclinical study, the addition of Selumetinib (AZD6244) to treatment with Tagrisso (osimertinib) resulted in increased inhibition of proliferation in lung cancer cell lines harboring EGFR L858R and T790M in culture (PMID: 28416483). 28416483
EGFR L858R EGFR T790M Advanced Solid Tumor sensitive EAI045 Preclinical - Cell culture Actionable In a preclinical study, EAI045 inhibited proliferation of transformed cells over expressing EGFR that harbors both L858R and T790M in culture, although at a concentration much higher than the biochemical IC50 of the compound (PMID: 27251290). 27251290
EGFR L858R EGFR T790M non-small cell lung carcinoma sensitive Afatinib + Ganetespib Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of Ganetespib and Gilotrif (afatinib) demonstrated improved antitumor activity compared to either agent alone in cell line xenograft models of non-small cell lung cancer harboring EGFR L858R and EGFR T790M (PMID: 25077897). 25077897
EGFR L858R EGFR T790M lung cancer sensitive Cetuximab + EAI045 Preclinical Actionable In a preclinical study, EAI045 and Erbitux (cetuximab) combination treatment induced tumor regression in an EGFR L858R/T790M-mutant-driven lung cancer mouse model (PMID: 27251290). 27251290
EGFR L858R EGFR T790M Advanced Solid Tumor sensitive Afatinib Preclinical - Cell culture Actionable In a preclinical study, Gilotrif (afatinib) inhibited EGFR signaling and proliferation of transformed cells expressing both EGFR L858R and EGFR T790M in culture (PMID: 29467275). 29467275
EGFR L858R EGFR T790M Advanced Solid Tumor sensitive Osimertinib Preclinical - Cell culture Actionable In a preclinical study, Tagrisso (osimertinib) inhibited EGFR signaling and proliferation of transformed cells expressing both EGFR L858R and EGFR T790M in culture (PMID: 29467275). 29467275
EGFR L858R EGFR T790M lung adenocarcinoma resistant Afatinib Clinical Study Actionable In a clinical study, acquired EGFR T790M mutations were detected in 47.6% (20/42) of lung adenocarcinoma patients with acquired resistance to Gilotrif (afatinib), with 10/20 of those patients harboring EGFR L858R as their primary EGFR mutation (PMID: 26862733). 26862733
EGFR L858R EGFR T790M Advanced Solid Tumor decreased response Neratinib Preclinical Actionable In a preclinical study, transformed cells expressing EGFR L858R and T790M demonstrated decreased sensitivity to Nerlynx (neratinib) in culture (PMID: 17085664). 17085664
EGFR L858R EGFR T790M non-small cell lung carcinoma sensitive Gedatolisib Preclinical Actionable In a preclinical study, Gedatolisib (PKI-587) inhibited growth of human non-small cell lung carcinoma cells harboring EGFR L858R EGFR T790M in culture (PMID: 21325073, PMID: 19238632). 21325073 19238632
EGFR L858R EGFR T790M lung cancer decreased response Afatinib Preclinical - Cell culture Actionable In a preclinical study, KEAP1 knockout resulted in decreased sensitivity to Gilotrif (afatinib) in a lung cancer cell line harboring EGFR L858R and T790M in culture (PMID: 28145866). 28145866
EGFR L858R EGFR T790M Advanced Solid Tumor sensitive Naquotinib Preclinical - Cell culture Actionable In a preclinical study, Naquotinib (ASP8273) inhibited EGFR signaling and proliferation of transformed cells expressing both EGFR L858R and EGFR T790M in culture (PMID: 29467275). 29467275
EGFR L858R EGFR T790M non-small cell lung carcinoma sensitive AV-412 Preclinical Actionable In a preclinical study, AV-412 inhibited EGFR signaling in a NSCLC cell line carrying the double EGFR mutant, L858R and T790M (PMID: 17888033). 17888033
EGFR L858R EGFR T790M lung cancer resistant AZD3759 Preclinical - Cell culture Actionable In a preclinical study, a lung cancer cell line harboring EGFR L858R and T790M did not demonstrate sensitivity to AZD3759 in culture (PMID: 27928026). 27928026
EGFR L858R EGFR T790M non-small cell lung carcinoma predicted - sensitive Ibrutinib + Trametinib Preclinical - Cell line xenograft Actionable In a preclinical study, Imbruvica (ibrutinib) and Mekinist (trametinib) combination treatment enhanced growth inhibition of non-small cell lung cancer cells harboring EGFR L858R and T790M compared to monotherapy in culture, but did not improve tumor suppression in cell line xenograft models (PMID: 26375053). 26375053
EGFR L858R EGFR T790M non-small cell lung carcinoma sensitive OBX1-012 Preclinical - Cell line xenograft Actionable In a preclinical study, non-small cell lung carcinoma cells harboring EGFR L858R and EGFR T790M were sensitive to treatment with OBX1-012, demonstrating decreased cell viability and apoptosis in vitro and inhibition of tumor growth in cell line xenograft models (PMID: 29754184). 29754184
EGFR L858R EGFR T790M non-small cell lung carcinoma predicted - resistant Vandetanib Preclinical - Cell line xenograft Actionable In a preclinical study, Caprelsa (vandetanib) did not inhibit Egfr activation and growth of non-small cell lung cancer cells harboring EGFR L858R and T790M in culture, but delayed the emergence of resistance in cell line xenograft models compared to EGFR tyrosine kinase inhibitors (PMID: 19447865). 19447865
EGFR L858R EGFR T790M non-small cell lung carcinoma sensitive Nazartinib Preclinical - Pdx & cell culture Actionable In a preclinical study, EGF816 inhibited proliferation of non-small cell lung cancer (NSCLC) cells harboring both EGFR L858R and EGFR T790M in culture, and induced tumor regression in NSCLC patient derived xenograft (PDX) models harboring both EGFR L858R and EGFR T790M (PMID: 26825170). 26825170
EGFR L858R EGFR T790M non-small cell lung carcinoma sensitive AZD9291 + JNJ-61186372 Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of Tagrisso (osimertinib) and JNJ-61186372 inhibited tumor growth in non-small cell lung cancer cell line xenograft models harboring EGFR L858R and EGFR T790M, and resulted in durable response following treatment cessation (PMID: 27216193). 27216193
EGFR L858R EGFR T790M non-small cell lung carcinoma sensitive Avitinib maleate Phase I Actionable In a Phase I trial, Avitinib maleate (AC0010) treatment resulted in an overall response rate of 36.5% (19/52) and a disease control rate of 75% (39/52) in non-small cell lung carcinoma patients harboring EGFR exon 19 deletions (33/52) or L858R (19/52) with acquired resistance to first generation Egfr tyrosine kinase inhibitors, 87% (45/52) of the patients also harbored EGFR T790M (PMID: 29626621). 29626621
EGFR L858R EGFR T790M non-small cell lung carcinoma sensitive Avitinib maleate Preclinical - Cell line xenograft Actionable In a preclinical study, non-small cell lung cancer cells harboring the double mutation, EGFR L858R and EGFR T790M, demonstrated sensitivity to treatment with Avitinib maleate (AC0010), resulting in inhibition of both cell growth and Egfr phosphorylation in culture, and tumor regression in xenograft models (PMID: 27573423). 27573423
EGFR L858R EGFR T790M non-small cell lung carcinoma sensitive WZ4002 + Trametinib Preclinical Actionable In a preclinical study, treatment with the combination of WZ4002 and Mekinist (trametinib) resulted in tumor regression, and decreased tumor rebound and increased survival compared to WZ4002 alone in non-small cell lung cancer mouse models expressing EGFR L858R and EGFR T790M (PMID: 26036643). 26036643
EGFR E746_A750del EGFR T790M EGFR C797S Advanced Solid Tumor no benefit Cetuximab Preclinical - Cell culture Actionable In a preclinical study, Erbitux (cetuximab) did not inhibit growth of transformed cells expressing a EGFR E746_A750del/T790M/C797S triple mutation in culture (PMID: 25948633). 25948633
EGFR I941R EGFR L858R EGFR T790M Advanced Solid Tumor sensitive EAI045 Preclinical - Cell culture Actionable In a preclinical study, transformed cells over expressing EGFR that harbors concomitant L858R, T790M and I941R mutations demonstrated increased sensitivity to EAI045 induced growth inhibition in culture (PMID: 27251290). 27251290
EGFR E746_A750del EGFR T790M lung adenocarcinoma resistant Gefitinib Clinical Study Actionable In a retrospective analysis, 4 patients with lung adenocarcinoma harboring EGFR E746_A750del that had developed Iressa (gefitinib) resistance were found to have acquired EGFR T790M mutations (PMID: 18981003). 18981003
EGFR E746_A750del EGFR T790M non-small cell lung carcinoma sensitive Afatinib Preclinical - Cell culture Actionable In a preclinical study, Gilotrif (afatinib) inhibited EGFR signaling and proliferation of non-small cell lung cancer cells harboring both EGFR E746_A750del and EGFR T790M in culture (PMID: 29467275). 29467275
EGFR E746_A750del EGFR T790M non-small cell lung carcinoma sensitive Osimertinib Preclinical - Cell culture Actionable In a preclinical study, Tagrisso (osimertinib) inhibited EGFR signaling and proliferation of non-small cell lung cancer cells harboring both EGFR E746_A750del and EGFR T790M in culture (PMID: 29467275). 29467275
EGFR E746_A750del EGFR T790M non-small cell lung carcinoma sensitive Naquotinib Preclinical - Cell culture Actionable In a preclinical study, Naquotinib (ASP8273) inhibited EGFR signaling and proliferation of non-small cell lung cancer cells harboring both EGFR E746_A750del and EGFR T790M in culture (PMID: 29467275). 29467275
EGFR E746_A750del EGFR T790M non-small cell lung carcinoma resistant Erlotinib Preclinical - Cell culture Actionable In a preclinical study, non-small cell lung cancer cells harboring both EGFR E746_A750del and EGFR T790M were resistant to Tarceva (erlotinib) in culture (PMID: 29467275). 29467275
EGFR E746_A750del EGFR T790M Advanced Solid Tumor sensitive Brigatinib Preclinical - Cell culture Actionable In a preclinical study, Alunbrig (brigatinib) inhibited growth of transformed cells expressing EGFR E746_A750del and T790M in culture (PMID: 27780853). 27780853
EGFR E746_A750del EGFR T790M non-small cell lung carcinoma sensitive WZ4002 + Trametinib Preclinical - Cell line xenograft Actionable In a preclinical study, treatment with the combination of WZ4002 and Mekinist (trametinib) inhibited tumor growth, and resulted in increased ERK inhibition and reduced tumor rebound compared to WZ4002 alone in non-small cell lung cancer cell line xenograft models harboring both EGFR E746_A750del and EGFR T790M (PMID: 26036643). 26036643
EGFR E746_A750del EGFR T790M lung adenocarcinoma resistant Erlotinib Clinical Study Actionable In a retrospective analysis, 3 of 4 patients with lung adenocarcinoma harboring EGFR E746_A750del and EGFR T790M were found to rapidly progress on Tarceva (erlotinib) therapy (PMID: 18981003). 18981003
EGFR D770delinsGY EGFR T790M Advanced Solid Tumor resistant Dacomitinib Preclinical - Cell culture Actionable In a preclinical study, acquisition of EGFR T790M was associated with resistance to dacomitinib in transformed cells expressing EGFR D770delinsGY (PMID: 28363995). 28363995
EGFR D770delinsGY EGFR T790M Advanced Solid Tumor sensitive Afatinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing an EGFR D770delinsGY/EGFR T790M double mutation demonstrated resistance to Gilotrif (afatinib) in culture (PMID: 28363995). 28363995
EGFR G719S EGFR T790M lung adenocarcinoma predicted - resistant Osimertinib Clinical Study Actionable In a clinical study, Tagrisso (osimertinib) treatment resulted in disease progression in a patient with lung adenocarcinoma harboring EGFR G719S and an acquired EGFR T790M, after her disease progressed while on Tarceva (erlotinib) and then on Gilotrif (afatinib) treatments (PMID: 29285266). 29285266
EGFR G719S EGFR T790M lung adenocarcinoma predicted - resistant Afatinib Clinical Study Actionable In a clinical study, EGFR T790M was identified as an acquired mutation in the tumor of a patient with lung adenocarcinoma harboring EGFR G719S, after her disease progressed while on Tarceva (erlotinib) and then on Gilotrif (afatinib) treatments (PMID: 29285266). 29285266
EGFR C797S EGFR T790M Advanced Solid Tumor sensitive OBX1-012 Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EGFR C797S and EGFR T790M were sensitive to treatment with OBX1-012 in culture, demonstrating decreased cell viability (PMID: 29754184). 29754184
EGFR L858R EGFR T790M MET amp MET D1228H D1228N D1231Y Y1230H lung adenocarcinoma unknown Cabozantinib + Osimertinib Clinical Study Actionable In a clinical case study, a patient with lung adenocarcinoma harboring EGFR L858R and EGFR T790M, MET amplification and MET D1228H, MET D1228N, MET Y1230H, and MET D1231Y demonstrated initial symptomatic improvement, decreased pleural effusion, and lung nodule shrinkage following treatment with the combination of Cometriq (Cabometyx, cabozantinib) and Tagrisso (osimertinib) (PMID: 29128427). 29128427
EGFR L858R EGFR T790M MET amp MET D1228H D1228N D1231Y Y1230H lung adenocarcinoma predicted - resistant Crizotinib + Osimertinib Clinical Study Actionable In a clinical case study, a patient with lung adenocarcinoma harboring EGFR L858R and EGFR T790M and MET amplification demonstrated progressive disease after 3 months of treatment with the combination of Tagrisso (osimertinib) and Xalkori (crizotinib) and was found to have acquired 4 MET mutations: MET D1228H, MET D1228N, MET Y1230H, and MET D1231Y (PMID: 29128427). 29128427
EGFR G719A EGFR L861Q EGFR T790M lung adenocarcinoma predicted - resistant Erlotinib Clinical Study Actionable In a clinical case study, EGFR T790M was detected at the time of progression in a patient with lung adenocarcinoma harboring EGFR G719A and L861Q that was treated with Tarceva (erlotinib) (PMID: 28343545). 28343545
EGFR G719A EGFR L861Q EGFR T790M lung adenocarcinoma predicted - sensitive Osimertinib Clinical Study Actionable In a clinical case study, Tagrisso (osimertinib) treatment resulted in partial response for over 8 months in a patient with lung adenocarcinoma harboring EGFR G719A, L861Q, and T790M that has progressed while on Tarceva (erlotinib) treatment (PMID: 28343545). 28343545
EGFR T790M ERBB2 over exp lung adenocarcinoma resistant Osimertinib Preclinical Actionable In a preclinical study, over expression of Erbb2 (Her2) in lung adenocarcinoma cells harboring EGFR T790M resulted in resistance to Tagrisso (osimertinib) in culture, consistent with ERBB2 (HER2) amplification identified in tumor samples of lung adenocarcinoma patients harboring EGFR T790M that developed resistance to Tagrisso (osimertinib) (PMID: 27252416). 27252416
EGFR T790M ERBB2 over exp lung adenocarcinoma resistant CO1686 Preclinical Actionable In a preclinical study, over expression of Erbb2 (Her2) in lung adenocarcinoma cells harboring EGFR T790M resulted in resistance to Rociletinib (CO-1686) in culture, consistent with ERBB2 (HER2) amplification identified in tumor samples of lung adenocarcinoma patients harboring EGFR T790M that developed resistance to Rociletinib (CO-1686) (PMID: 27252416). 27252416
EGFR L858R EGFR T790M PIK3CA G118D non-small cell lung carcinoma sensitive Pimasertib + Regorafenib Preclinical - Cell culture Actionable In a preclinical study, Pimasertib (MSC1936369B) and Stivarga (regorafenib) synergistically inhibited proliferation of non-small cell lung cancer cells harboring EGFR L858R, EGFR T790M, and PIK3CA G118D in culture (PMID: 23629727). 23629727
EGFR L858R EGFR T790M PIK3CA G118D non-small cell lung carcinoma sensitive Pimasertib + BEZ235 Preclinical - Cell line xenograft Actionable In a preclinical study, Pimasertib (MSC1936369B) and BEZ235 combination treatment inhibited tumor growth in non-small cell lung cancer cell line xenograft models harboring EGFR L858R, EGFR T790M, and PIK3CA G118D in culture (PMID: 23629727). 23629727
EGFR L858R EGFR T790M PIK3CA G118D non-small cell lung carcinoma sensitive Everolimus + Pimasertib Preclinical - Cell culture Actionable In a preclinical study, Pimasertib (MSC1936369B) and Afinitor (everolimus) synergistically inhibited proliferation of non-small cell lung cancer cells harboring EGFR L858R, EGFR T790M, and PIK3CA G118D in culture (PMID: 23629727). 23629727
EGFR L858R EGFR T790M PIK3CA G118D non-small cell lung carcinoma sensitive Pimasertib + Sorafenib Preclinical - Cell line xenograft Actionable In a preclinical study, Pimasertib (MSC1936369B) and Nexavar (sorafenib) synergistically inhibited Mapk and Akt signaling, resulted in growth inhibition of non-small cell lung cancer cells harboring EGFR L858R, EGFR T790M, and PIK3CA G118D in culture and in cell line xenograft models (PMID: 23629727). 23629727
EGFR L858R EGFR T790M PIK3CA G118D non-small cell lung carcinoma decreased response Pimasertib Preclinical - Cell culture Actionable In a preclinical study, non-small cell lung cancer cells harboring EGFR L858R, T790M, and PIK3CA G118D demonstrated decreased response to Pimasertib (MSC1936369B) in culture (PMID: 23629727). 23629727
EGFR E746_S752del EGFR T790M EGFR P794L non-small cell lung carcinoma predicted - sensitive Afatinib Clinical Study Actionable In a clinical case study, Gilotrif (afatinib) treatment resulted in rapid clinical response in a patient with non-small cell lung carcinoma harboring an EGFR exon 19 deletion (E746_S752del), EGFR T790M and EGFR P794L (PMID: 29704676). 29704676
EGFR E746_S752del EGFR T790M EGFR P794L non-small cell lung carcinoma predicted - resistant Osimertinib Clinical Study Actionable In a clinical case study, Tagrisso (osimertinib) treatment resulted in initial response in a patient with non-small cell lung carcinoma harboring an EGFR exon 19 deletion (E746_S752del) and T790M, however, the disease progressed 20 months after treatment started, and EGFR P794L was identified by liquid biopsy at the time of progression (PMID: 29704676). 29704676
EGFR act mut EGFR C797S EGFR T790M non-small cell lung carcinoma resistant Naquotinib Phase I Actionable In a Phase I trial, three non-small cell lung carcinoma patients initially harboring EGFR T790M and/or an EGFR activating mutation demonstrated a partial response to ASP8273 treatment, but later progressed, demonstrating in cell-free DNA, a reemergence of EGFR T790M and/or the EGFR activating mutation and EGFR C797S (PMID: 28954786; NCT02113813). 28954786
EGFR L858R EGFR T790M NRAS Q61K non-small cell lung carcinoma resistant Osimertinib Preclinical Actionable In a preclinical study, non-small cell lung cancer cells harboring EGFR L858R, EGFR T790M, and NRAS Q61K were resistant to Tagrisso (osimertinib) in culture (PMID: 25870145). 25870145
EGFR E746_A750del EGFR T790M EGFR Q791R Advanced Solid Tumor resistant CO1686 Preclinical Actionable In a preclinical study, transformed cells expressing an EGFR E746_A750del/EGFR T790M/EGFR Q791R triple mutation demonstrated resistance to Rociletinib (CO-1686) in culture (PMID: 25948633). 25948633
EGFR E746_A750del EGFR T790M EGFR Q791R Advanced Solid Tumor sensitive Osimertinib Preclinical Actionable In a preclinical study, AZD9291 inhibited growth of transformed cells expressing an EGFR E746_A750del/EGFR T790M/EGFR Q791R triple mutation in culture (PMID: 25948633). 25948633
EGFR T790M MET amp lung adenocarcinoma resistant CO1686 Preclinical Actionable In a preclinical study, expression of EGFR T790M in MET-amplified lung adenocarcinoma cells resulted in resistance to Rociletinib (CO-1686) in culture, consistent with MET amplification identified in tumor samples of lung adenocarcinoma patients harboring EGFR T790M that developed resistance to Rociletinib (CO-1686) (PMID: 27252416). 27252416
EGFR T790M MET amp non-small cell lung carcinoma resistant CO1686 Clinical Study Actionable In an analysis of EGFR T790M-positive non-small cell lung cancer patients, emergence of MET amplification was identified in 26% (28/43) of patients with acquired resistance to Rociletinib (CO1686), and patients with MET amplification prior to Rociletinib (CO1686) treatment demonstrated a decreased response compared to patients without MET amplification (PMID: 27283993). 27283993
EGFR T790M MET amp lung adenocarcinoma resistant Osimertinib Preclinical Actionable In a preclinical study, expression of EGFR T790M in MET-amplified lung adenocarcinoma cells resulted in resistance to Tagrisso (osimertinib) in culture, consistent with MET amplification identified in tumor samples of lung adenocarcinoma patients harboring EGFR T790M that developed resistance to Tagrisso (osimertinib) (PMID: 27252416). 27252416
EGFR exon 19 del EGFR T790M NRAS Q61K non-small cell lung carcinoma resistant Osimertinib Preclinical Actionable In a preclinical study, non-small cell lung cancer cells harboring EGFR exon 19 deletion, EGFR T790M, and NRAS Q61K were resistant to Tagrisso (osimertinib) in culture (PMID: 25870145). 25870145
EGFR del exon 19 EGFR T790M non-small cell lung carcinoma sensitive WZ4002 Preclinical Actionable In a preclinical study, WZ4002 inhibited EGFR signaling and cell growth in 1st generation TKI-resistant non-small cell lung carcinoma cells harboring EGFR exon 19 deletion and EGFR T790M in culture (PMID: 25964297). 25964297
EGFR del exon 19 EGFR T790M non-small cell lung carcinoma resistant Afatinib Preclinical Actionable In a preclinical study, non-small cell lung cancer cells harboring EGFR exon 19 deletion became resistant to Gilotrif (afatinib) after the emergence of EGFR T790M in culture (PMID: 25870145). 25870145
EGFR del exon 19 EGFR T790M lung cancer sensitive Osimertinib + PF-573328 + Saracatinib Preclinical - Cell culture Actionable In a preclinical study, the combination of Tagrisso (osimertinib) with PF-573328 and Saracatinib (AZD0530) resulted in increased inhibition of AKT, FAK, and SFK phosphorylation and growth compared to Tagrisso (osimertinib) alone in a lung cancer cell line harboring an EGFR exon 19 deletion and T790M in culture (PMID: 28416483). 28416483
EGFR del exon 19 EGFR T790M lung cancer resistant Cetuximab + EAI045 Preclinical Actionable In a preclinical study, EAI045 and Erbitux (cetuximab) combination treatment did not induced response in an EGFR exon 19 deletion/T790M-driven lung cancer mouse model (PMID: 27251290). 27251290
EGFR del exon 19 EGFR T790M non-small cell lung carcinoma predicted - sensitive Osimertinib + Ramucirumab Phase I Actionable In a Phase I trial, Cyramza (ramucirumab) and Tagrisso (osimertinib) combination treatment resulted in an objective response rate of 76% (19/25, 1 complete response, 18 partial response), and stable disease in 16% (4/25) of EGFR-mutant (exon 19 deletion or L858R) non-small cell lung cancer patients harboring EGFR T790M, who progressed on first-line EGFR TKI therapy (J Clin Oncol 36, 2018 (suppl; abstr 9053); NCT02789345). detail...
EGFR del exon 19 EGFR T790M non-small cell lung carcinoma resistant Gefitinib Preclinical Actionable In a preclinical study, non-small cell lung cancercarcinoma cells harboring EGFR exon 19 deletion and EGFR T790M were resistant to Iressa (gefitinib) induced suppression of EGFR signaling and growth inhibition in culture (PMID: 25964297). 25964297
EGFR del exon 19 EGFR T790M non-small cell lung carcinoma resistant Gefitinib Clinical Study Actionable In a clinical case study, Iressa (gefitinib) treatment resulted in initial response in a patient with non-small cell lung carcinoma harboring an EGFR exon 19 deletion, however, the disease progressed 3 years after initial treatment and EGFR T790M was identified at the time of progression (PMID: 29704676). 29704676
EGFR del exon 19 EGFR T790M lung cancer sensitive BKM120 + Osimertinib Preclinical - Cell culture Actionable In a preclinical study, treatment with the combination of Buparlisib (BKM120) and Tagrisso (osimertinib) resulted in increased inhibition of AKT phosphorylation and proliferation compared to Tagrisso (osimertinib) alone in a lung cancer cell line harboring an EGFR exon 19 deletion and T790M in culture (PMID: 28416483). 28416483
EGFR del exon 19 EGFR T790M Advanced Solid Tumor sensitive WZ4002 Preclinical Actionable In a preclinical study, WZ4002 inhibited EGFR signaling in transformed human cells over expressing EGFR exon 19 deletion and EGFR T790M in culture (PMID: 25964297). 25964297
EGFR del exon 19 EGFR T790M Advanced Solid Tumor resistant Cetuximab + EAI045 Preclinical - Cell culture Actionable In a preclinical study, combination of EAI045 and Erbitux (cetuximab) did not inhibit proliferation of transformed cells over expressing EGFR that harbors both exon 19 deletion and T790M in culture (PMID: 27251290). 27251290
EGFR del exon 19 EGFR T790M Advanced Solid Tumor sensitive BGB-283 Preclinical - Cell culture Actionable In a preclinical study, BGB-283 inhibited proliferation of transformed cells over expressing both EGFR exon 19 deletion mutation and T790M in culture (PMID: 26208524). 26208524
EGFR del exon 19 EGFR T790M lung cancer sensitive Osimertinib + Bosutinib + PF-573328 Preclinical - Cell culture Actionable In a preclinical study, the combination of Tagrisso (osimertinib) with PF-573328 and Bosulif (bosutinib) resulted in increased inhibition of AKT, FAK, and SFK phosphorylation and growth compared to Tagrisso (osimertinib) alone in a lung cancer cell line harboring an EGFR exon 19 deletion and T790M in culture (PMID: 28416483). 28416483
EGFR del exon 19 EGFR T790M lung cancer sensitive GSK2334470 + Osimertinib Preclinical - Cell culture Actionable In a preclinical study, treatment with the combination of GSK2334470 and Tagrisso (osimertinib) resulted in increased inhibition of AKT phosphorylation and proliferation compared to Tagrisso (osimertinib) alone in a lung cancer cell line harboring an EGFR exon 19 deletion and T790M in culture (PMID: 28416483). 28416483
EGFR del exon 19 EGFR T790M non-small cell lung carcinoma sensitive CO1686 Phase Ib/II Actionable In a Phase Ib/II trial, treatment with Rociletinib (CO-1686) resulted in an objective response rate of 64.3% (18/28) in non-small cell lung cancer patients harboring both EGFR exon 19 deletions and EGFR T790M (PMID: 25923550). 25923550
EGFR del exon 19 EGFR T790M Advanced Solid Tumor resistant Gefitinib Preclinical Actionable In a preclinical study, transformed human cells over expressing EGFR exon 19 deletion and EGFR T790M were resistant to Iressa (gefitinib) induced suppression of EGFR signaling in culture (PMID: 25964297). 25964297
EGFR del exon 19 EGFR T790M Advanced Solid Tumor resistant EAI045 Preclinical - Cell culture Actionable In a preclinical study, EAI045 did not inhibit proliferation of transformed cells over expressing EGFR that harbors both exon 19 deletion and T790M in culture (PMID: 27251290). 27251290
EGFR del exon 19 EGFR T790M lung adenocarcinoma resistant Afatinib Clinical Study Actionable In an analysis of lung adenocarcinoma patients treated with Gilotrif (afatinib), second-site EGFR T790M mutations were detected in 47.6% (20/42) of patients with acquired resistance, with 9/20 patients harboring primary EGFR exon 19 deletion mutations (PMID: 26862733). 26862733
EGFR del exon 19 EGFR T790M non-small cell lung carcinoma sensitive Osimertinib Phase III Actionable In a Phase III trial, third-line treatment with Tagrisso (osimertinib) resulted in improved median progression-free survival compared to treatment with the combination of Taxotere (docetaxel) and Avastin (bevacizumab) (10.2 mo vs. 2.95 mo., HR=0.23), and a an overall response rate of 61.6% (45/73) compared to 8.3% (6/72), in patients with non-squamous non-small cell lung cancer harboring EGFR T790M with either EGFR L858R or an EGFR exon 19 deletion (PMID: 29858027, NCT02959749). 29858027
EGFR del exon 19 EGFR T790M non-small cell lung carcinoma sensitive Osimertinib Clinical Study Actionable In a clinical case study, Tagrisso (osimertinib) resulted in a partial response and stable disease of brain metastases in a NSCLC patient harboring EGFR exon 19 deletion and a secondary resistance mutation, EGFR T790M, which occurred post Iressa (gefitinib) therapy (PMID: 27435396). 27435396
EGFR del exon 19 EGFR T790M non-small cell lung carcinoma sensitive Osimertinib Phase I Actionable In a Phase I trial, AZD9291 treatment resulted in a response rate of 64% (49/77) in NSCLC patients that harbored both EGFR exon 19 deletions and T790M mutations (PMID: 25923549). 25923549
EGFR del exon 19 EGFR T790M Advanced Solid Tumor sensitive Afatinib Preclinical Actionable In a preclinical study, Gilotrif (afatinib) inhibited EGFR signaling in transformed human cells over expressing EGFR exon 19 deletion and EGFR T790M in culture (PMID: 25964297). 25964297
EGFR del exon 19 EGFR T790M non-small cell lung carcinoma sensitive TAE226 Preclinical - Cell line xenograft Actionable In a preclinical study, TAE226 treatment inhibited cell proliferation and decreased xenograft tumor size of non-small cell lung carcinoma cell lines harboring both EGFR T790M and EGFR Exon 19 deletion mutations (PMID: 26090892). 26090892
EGFR L747_T751delinsP EGFR T790M lung adenocarcinoma resistant Gefitinib Clinical Study Actionable In a retrospective analysis, a patient with lung adenocarcinoma harboring EGFR L747_T751delinsP that had developed Iressa (gefitinib) resistance was demonstrated to have acquired an EGFR T790M mutation (PMID: 18981003). 18981003
EGFR L747_T751delinsP EGFR T790M lung adenocarcinoma resistant Erlotinib Clinical Study Actionable In a retrospective analysis, a patient with lung adenocarcinoma harboring EGFR L747_T751delinsP and EGFR T790M was found to rapidly progress on Tarceva (erlotinib) therapy (PMID: 18981003). 18981003
EGFR L747_P753delinsS + EGFR T790M Advanced Solid Tumor resistant Erlotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing both EGFR L747_P753delinsS and EGFR T790M were resistant to Tarceva (erlotinib) in culture (PMID: 29467275). 29467275
EGFR L747_P753delinsS + EGFR T790M Advanced Solid Tumor sensitive Afatinib Preclinical - Cell culture Actionable In a preclinical study, Tagrisso (osimertinib) inhibited EGFR signaling and proliferation of transformed cells expressing both EGFR L747_P753delinsS and EGFR T790M in culture (PMID: 29467275). 29467275
EGFR L747_P753delinsS + EGFR T790M Advanced Solid Tumor sensitive Naquotinib Preclinical - Cell culture Actionable In a preclinical study, Naquotinib (ASP8273) inhibited EGFR signaling and proliferation of transformed cells expressing both EGFR L747_P753delinsS and EGFR T790M in culture (PMID: 29467275). 29467275
EGFR L747_P753delinsS + EGFR T790M Advanced Solid Tumor sensitive Osimertinib Preclinical - Cell culture Actionable In a preclinical study, Tagrisso (osimertinib) inhibited EGFR signaling and proliferation of transformed cells expressing both EGFR L747_P753delinsS and EGFR T790M in culture (PMID: 29467275). 29467275
EGFR E746_A750del EGFR T790M EGFR L718Q non-small cell lung carcinoma sensitive Osimertinib Preclinical Actionable In a preclinical study, AZD9291 inhibited growth of non-small cell lung cancer cells harboring EGFR E746_A750del and EGFR T790M and ectopically expressing an EGFR E746_A750del/EGFR T790M/EGFR L718Q triple mutation in culture (PMID: 25948633). 25948633
EGFR E746_A750del EGFR T790M EGFR L718Q Advanced Solid Tumor resistant CO1686 Preclinical Actionable In a preclinical study, transformed cells expressing an EGFR E746_A750del/EGFR T790M/EGFR L718Q triple mutation demonstrated resistance to Rociletinib (CO-1686) in culture (PMID: 25948633). 25948633
EGFR E746_A750del EGFR T790M EGFR L718Q Advanced Solid Tumor resistant Osimertinib Preclinical Actionable In a preclinical study, transformed cells expressing an EGFR E746_A750del/EGFR T790M/EGFR L718Q triple mutation demonstrated resistance to AZD9291 in culture (PMID: 25948633). 25948633
EGFR E746_A750del EGFR T790M EGFR L718Q non-small cell lung carcinoma resistant CO1686 Preclinical Actionable In a preclinical study, expression of an EGFR E746_A750del/EGFR T790M/EGFR L718Q triple mutation conferred resistance to Rociletinib (CO-1686) in non-small cell lung cancer cells harboring EGFR E746_A750del and EGFR T790M in culture (PMID: 25948633). 25948633
EGFR L747_S752del EGFR T790M lung adenocarcinoma resistant Gefitinib Clinical Study Actionable In a retrospective analysis, a patient with lung adenocarcinoma harboring EGFR L747_S752del that developed Iressa (gefitinib) resistance was demonstrated to have acquired an EGFR T790M mutation (PMID: 18981003). 18981003
EGFR L747_S752del EGFR T790M lung adenocarcinoma resistant Erlotinib Clinical Study Actionable In a retrospective analysis, a patient with lung adenocarcinoma harboring EGFR L747_S752del and EGFR T790M was found to rapidly progress on Tarceva (erlotinib) therapy (PMID: 18981003). 18981003
EGFR exon 19 del EGFR T790M lung cancer sensitive Osimertinib + TAK-632 Preclinical - Cell culture Actionable In a preclinical study, treatment with the combination of TAK-632 and Tagrisso (osimertinib) resulted in increased inhibition of ERK phosphorylation and proliferation compared to either agent alone in a lung cancer cell line harboring an EGFR exon 19 deletion and T790M in culture (PMID: 28416483). 28416483
EGFR exon 19 del EGFR T790M lung cancer sensitive Osimertinib + Selumetinib Preclinical - Cell culture Actionable In a preclinical study, treatment with the combination of Selumetinib (AZD6244) and Tagrisso (osimertinib) resulted in increased inhibition of ERK phosphorylation and proliferation compared to either agent alone in a lung cancer cell line harboring an EGFR exon 19 deletion and T790M in culture (PMID: 28416483). 28416483
EGFR exon 19 del EGFR T790M lung cancer sensitive Dasatinib + Osimertinib Preclinical - Cell line xenograft Actionable In a preclinical study, Tagrisso (osimertinib) and Sprycel (dasatinib) in combination resulted in increased PARP cleavage and inhibition of proliferation in a lung cancer cell line harboring an EGFR exon 19 deletion and T790M compared to Tagrisso (osimertinib) alone, and inhibited tumor growth in xenograft models, with 3 out of 7 models demonstrating no tumor rebound after cessation of therapy (PMID: 28416483). 28416483
EGFR exon 19 del EGFR T790M non-small cell lung carcinoma sensitive OBX1-012 Preclinical - Cell culture Actionable In a preclinical study, non-small cell lung carcinoma cells harboring EGFR exon 19 del and EGFR T790M , resistant to Iressa (gefitinib) and Tarceva (erlotinib), were sensitive to treatment with OBX1-012, demonstrating decreased cell viability and apoptosis in vitro (PMID: 29754184). 29754184
EGFR exon 19 del EGFR T790M non-small cell lung carcinoma predicted - sensitive Avitinib maleate Phase I Actionable In a Phase I trial, Avitinib maleate (AC0010) treatment resulted in an overall response rate of 36.5% (19/52) and a disease control rate of 75% (39/52) in non-small cell lung carcinoma patients harboring EGFR exon 19 deletions (33/52) or L858R (19/52) with acquired resistance to first generation Egfr tyrosine kinase inhibitors, 87% (45/52) of the patients also harbored EGFR T790M (PMID: 29626621). 29626621
EGFR C797S EGFR L858R EGFR T790M Advanced Solid Tumor resistant Naquotinib Preclinical - Cell culture Actionable In a preclinical study, transformed cells expressing a combination of EGFR C797S, EGFR L858R, and EGFR T790M were resistant to Naquotinib (ASP8273) in culture (PMID: 29467275). 29467275
EGFR C797S EGFR L858R EGFR T790M Advanced Solid Tumor resistant Nazartinib Preclinical - Cell culture Actionable In a preclinical study, overexpression of EGFR C797S in addition to EGFR L858R and T790M conferred resistance to Nazartinib (EGF816) in transformed cells in culture (PMID: 29285266) 29285266
EGFR C797S EGFR L858R EGFR T790M Advanced Solid Tumor resistant Afatinib Preclinical - Cell culture Actionable In a preclinical study, overexpression of EGFR C797S in addition to EGFR L858R and T790M conferred resistance to Gilotrif (afatinib) in transformed cells in culture (PMID: 29285266). 29285266
EGFR C797S EGFR L858R EGFR T790M Advanced Solid Tumor resistant CO1686 Preclinical Actionable In a preclinical study, EGFR C797S conferred resistance to growth inhibition by Rociletinib (CO-1686) when expressed on the same allele as EGFR L858R and T790M in transformed cells in culture (PMID: 25939061). 25939061
EGFR C797S EGFR L858R EGFR T790M Advanced Solid Tumor sensitive Cetuximab Preclinical - Cell culture Actionable In a preclinical study, Erbitux (cetuximab) inhibited growth of transformed cells expressing a EGFR L858R/T790M/C797S triple mutation in culture (PMID: 25948633). 25948633
EGFR C797S EGFR L858R EGFR T790M Advanced Solid Tumor resistant Osimertinib Preclinical Actionable In a preclinical study, expression of EGFR C797S on the same allele as both EGFR L858R and T790M in transformed cell lines resulted in resistance to growth inhibition by Tagrisso (osimertinib) in culture (PMID: 25939061). 25939061
EGFR C797S EGFR L858R EGFR T790M lung cancer sensitive Cetuximab + EAI045 Preclinical Actionable In a preclinical study, EAI045 and Erbitux (cetuximab) combination treatment induced tumor regression in an EGFR L858R/T790M/C797S-mutant-driven lung cancer mouse model (PMID: 27251290). 27251290
EGFR C797S EGFR L858R EGFR T790M Advanced Solid Tumor predicted - resistant OBX1-012 Preclinical - Cell culture Actionable In a preclinical study, transformed cells co-expressing EGFR C797S, EGFR L858R, and EGFR T790M did not respond to treatment with OBX1-012 in culture (PMID: 29754184). 29754184
EGFR C797S EGFR L858R EGFR T790M Advanced Solid Tumor resistant Erlotinib Preclinical - Cell culture Actionable In a preclinical study, overexpression of EGFR C797S in addition to EGFR L858R and T790M conferred resistance to Tarceva (erlotinib) in transformed cells in culture (PMID: 29285266) 29285266
EGFR C797S EGFR L858R EGFR T790M Advanced Solid Tumor sensitive Cetuximab + EAI045 Preclinical - Cell culture Actionable In a preclinical study, EAI045 and Erbitux (cetuximab) synergistically inhibited proliferation of transformed cells over expressing EGFR that harbors concomitant C797S, L858R and T790M mutations in culture (PMID: 27251290). 27251290
EGFR L858R EGFR T790M MET amp lung adenocarcinoma predicted - sensitive Crizotinib + Osimertinib Clinical Study Actionable In a clinical case study, a lung adenocarcinoma patient with EGFR L858R, EGFR T790M, and MET amplification demonstrated a partial response in her lung lesions and an approximately 90% reduction in the retroperitoneal lymph node and right adrenal gland, and progression-free survival lasting 3 months following treatment with the combination of Tagrisso (osimertinib) and Xalkori (crizotinib) (PMID: 29128427). 29128427
EGFR L858R EGFR T790M MET amp lung adenocarcinoma predicted - resistant Osimertinib Clinical Study Actionable In a clinical case study, a patient with lung adenocarcinoma harboring EGFR L858R and EGFR T790M progressed after 19 months on Tagrisso (osimertinib), and was found to have acquired MET amplification (PMID: 29128427). 29128427
EGFR act mut EGFR T790M non-small cell lung carcinoma no benefit AUY922 + Erlotinib Phase Ib/II Actionable In a Phase Ib/II clinical trial, the combination of AUY922 and Tarceva (erlotinib) demonstrated limited clinical benefit in patients with EGFR-mutant non-small cell carcinoma with acquired resistance to EGFR tyrosine kinase inhibitors, including patients with EGFR T790M, with 16% (4/25) patients achieving partial response (PMID: 25870087). 25870087
EGFR act mut EGFR T790M lung adenocarcinoma sensitive Bevacizumab + Erlotinib Phase II Actionable In a Phase II trial, Avastin (bevacizumab) and Tarceva (erlotinib) combination treatment resulted in a median progression-free survival of 16.0 months and a 12 month progression-free survival of 68% (25/37) in treatment-naive lung adenocarcinoma patients harboring activating EGFR mutations (exon 19 deletion or L858R) and EGFR T790M (PMID: 28408243). 28408243
EGFR act mut EGFR T790M non-small cell lung carcinoma sensitive Naquotinib Phase I Actionable In a Phase I trial, treatment with ASP8273 resulted in a partial response in 41% (19/46) of non-small cell lung carcinoma patients co-harboring EGFR T790M and an EGFR activating mutation, demonstrating almost undetectable levels of the mutations in cell-free DNA (PMID: 28954786; NCT02113813). 28954786
EGFR C797S EGFR del exon 19 EGFR T790M lung adenocarcinoma resistant WZ4002 Preclinical Actionable In a preclinical study, lung adenocarcinoma cells over expressing EGFR exon 19 deletion, EGFR T790M and EGFR C797S in cis were resistant to WZ4002 induced suppression of EGFR signaling and growth inhibition in culture (PMID: 25964297). 25964297
EGFR C797S EGFR del exon 19 EGFR T790M non-small cell lung carcinoma resistant Osimertinib Phase I Actionable In a Phase I clinical trial, 40% (6/15) of non-small cell lung cancer patients harboring an EGFR exon 19 deletion and EGFR T790M developed resistance to Tagrisso (osimertinib) due to acquired EGFR C797S mutations (PMID: 25939061). 25939061
EGFR C797S EGFR del exon 19 EGFR T790M non-small cell lung carcinoma conflicting Gefitinib + WZ4002 Preclinical Actionable In a preclinical study, non-small cell lung carcinoma cells harboring EGFR exon 19 deletion, EGFR T790M and EGFR C797S were resistant to the combination of Iressa (gefitinib) and WZ4002 when T790M and C797S were in cis, but were sensitive when EGFR T790M and EGFR C797S were in trans (PMID: 25964297). 25964297
EGFR C797S EGFR del exon 19 EGFR T790M lung adenocarcinoma resistant Afatinib Preclinical Actionable In a preclinical study, lung adenocarcinoma cells over expressing EGFR exon 19 deletion, EGFR T790M and EGFR C797S in cis were resistant to Gilotrif (afatinib) induced suppression of EGFR signaling and growth inhibition in culture (PMID: 25964297). 25964297
EGFR C797S EGFR del exon 19 EGFR T790M Advanced Solid Tumor conflicting Gefitinib + WZ4002 Preclinical Actionable In a preclinical study, Iressa (gefitinib) and WZ4002 combination treatment resulted in complete inhibition of EGFR signaling in transformed human cells over expressing EGFR exon 19 deletion, EGFR T790M and EGFR C797S when T790M and C797S were expressed in trans, but no EGFR inhibition when T790M and C797S were expressed in cis (PMID: 25964297). 25964297
EGFR C797S EGFR del exon 19 EGFR T790M Advanced Solid Tumor resistant Afatinib Preclinical Actionable In a preclinical study, transformed human cells over expressing EGFR exon 19 deletion, EGFR T790M and EGFR C797S in cis were resistant to Gilotrif (afatinib) induced suppression of EGFR signaling in culture (PMID: 25964297). 25964297
EGFR C797S EGFR del exon 19 EGFR T790M non-small cell lung carcinoma resistant Gefitinib Preclinical Actionable In a preclinical study, non-small cell lung carcinoma cells harboring EGFR exon 19 deletion, EGFR T790M and EGFR C797S were resistant to Iressa (gefitinib) induced suppression of EGFR signaling and growth inhibition in culture, regardless of the allelic context of EGFR T790M and EGFR C797S (PMID: 25964297). 25964297
EGFR C797S EGFR del exon 19 EGFR T790M Advanced Solid Tumor resistant Osimertinib Preclinical Actionable In a preclinical study, expression of EGFR C797S on the same allele as an EGFR exon 19 deletion and EGFR T790M in transformed cell lines resulted in resistance to growth inhibition by Tagrisso (osimertinib) in culture (PMID: 25939061). 25939061
EGFR C797S EGFR del exon 19 EGFR T790M lung adenocarcinoma resistant Gefitinib Preclinical Actionable In a preclinical study, lung adenocarcinoma cells over expressing EGFR exon 19 deletion, EGFR T790M and EGFR C797S in cis were resistant to Iressa (gefitinib) induced suppression of EGFR signaling and growth inhibition in culture (PMID: 25964297). 25964297
EGFR C797S EGFR del exon 19 EGFR T790M Advanced Solid Tumor conflicting WZ4002 Preclinical Actionable In a preclinical study, WZ4002 treatment resulted in partial inhibition of EGFR signaling in transformed human cells over expressing EGFR exon 19 deletion, EGFR T790M and EGFR C797S when T790M and C797S were expressed in trans, but no EGFR inhibition when T790M and C797S were expressed in cis (PMID: 25964297). 25964297
EGFR C797S EGFR del exon 19 EGFR T790M non-small cell lung carcinoma resistant WZ4002 Preclinical Actionable In a preclinical study, non-small cell lung carcinoma cells harboring EGFR exon 19 deletion, EGFR T790M and EGFR C797S were resistant to WZ4002 induced suppression of EGFR signaling and growth inhibition in culture, regardless of the allelic context of EGFR T790M and EGFR C797S (PMID: 25964297). 25964297
EGFR C797S EGFR del exon 19 EGFR T790M Advanced Solid Tumor resistant CO1686 Preclinical Actionable In a preclinical study, EGFR C797S conferred resistance to growth inhibition by Rociletinib (CO-1686) when expressed on the same allele as an EGFR exon 19 deletion mutation and T790M in transformed cells in culture (PMID: 25939061). 25939061
EGFR C797S EGFR del exon 19 EGFR T790M non-small cell lung carcinoma resistant Afatinib Preclinical Actionable In a preclinical study, non-small cell lung carcinoma cells harboring EGFR exon 19 deletion, EGFR T790M and EGFR C797S in cis were resistant to Gilotrif (afatinib) induced suppression of EGFR signaling and growth inhibition in culture (PMID: 25964297). 25964297
EGFR C797S EGFR del exon 19 EGFR T790M Advanced Solid Tumor conflicting Gefitinib Preclinical Actionable In a preclinical study, Iressa (gefitinib) treatment resulted in partial inhibition of EGFR signaling in transformed human cells over expressing EGFR exon 19 deletion, EGFR T790M and EGFR C797S when T790M and C797S were expressed in trans, but no EGFR inhibition when T790M and C797S were expressed in cis (PMID: 25964297). 25964297
EGFR L858R EGFR Q791R EGFR T790M Advanced Solid Tumor resistant CO1686 Preclinical Actionable In a preclinical study, transformed cells expressing an EGFR L858R/EGFR T790M/EGFR Q791R triple mutation demonstrated resistance to Rociletinib (CO-1686) in culture (PMID: 25948633). 25948633
EGFR L858R EGFR Q791R EGFR T790M Advanced Solid Tumor sensitive Osimertinib Preclinical Actionable In a preclinical study, AZD9291 inhibited growth of transformed cells expressing an EGFR L858R/EGFR T790M/EGFR Q791R triple mutation in culture (PMID: 25948633). 25948633
EGFR T790M EGFR mut non-small cell lung carcinoma decreased response Nivolumab Clinical Study Actionable In a retrospective study, Opdivo (nivolumab) treatment after disease progression during EGFR tyrosine kinase inhibitors resulted in longer median progression-free survival (2.1 vs 1.3 months, HR=0.48, p=0.099) in T790M-negative, EGFR mutant non-small cell lung cancer patients compared to T790M-positive patients (PMID: 28407039). 28407039
EGFR exon 19 del EGFR T790M MET amp lung adenocarcinoma predicted - sensitive Crizotinib Clinical Study Actionable In a clinical case study, a lung adenocarcinoma patient harboring an EGFR exon 19 deletion and EGFR T790M and resistance to Tagrisso (osimertinib) following acquired MET amplification, demonstrated some improvement in symptoms with Xalkori (crizotinib) treatment (PMID: 27393507). 27393507
EGFR exon 19 del EGFR T790M MET amp lung adenocarcinoma resistant Osimertinib Clinical Study Actionable In a clinical case study, a lung adenocarcinoma patient harboring an EGFR exon 19 deletion and EGFR T790M developed resistance to Tagrisso (osimertinib), and was found to have acquired high level amplification of MET (PMID: 27393507). 27393507
EGFR L858R EGFR L844V EGFR T790M Advanced Solid Tumor resistant CO1686 Preclinical Actionable In a preclinical study, transformed cells expressing an EGFR L858R/EGFR T790M/EGFR L844V triple mutation demonstrated resistance to Rociletinib (CO-1686) in culture (PMID: 25948633). 25948633
EGFR L858R EGFR L844V EGFR T790M Advanced Solid Tumor sensitive Osimertinib Preclinical Actionable In a preclinical study, AZD9291 inhibited growth of transformed cells expressing an EGFR L858R/EGFR T790M/EGFR L844V triple-mutation in culture (PMID: 25948633). 25948633