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    BIOMARKER:

    EGFR C797S

    i
    Other names: EGFR, ERBB, ERBB1, Epidermal growth factor receptor
    Entrez ID:
    1956
    Related biomarkers:
    Expression
    Mutation
    CNA
    Fusion
    Others
    Related tests:
    11ms
    Report of 20 pts w/ #EGFR NSCLC + #MET amplification-mediated resistance to osimertinib in #JTOCRR from Dr. @LeXiuning & team. Adding MET TKI had RR 35%, median time on treatment 27m, 3 cases of pneumonitis. Resistance included MET D1246H, EGFR C797S. https://t.co/KJNnA1NV6r (@StephenVLiu)
    Clinical
    |
    EGFR (Epidermal growth factor receptor) • MET (MET proto-oncogene, receptor tyrosine kinase)
    |
    MET amplification • EGFR C797S
    |
    Tagrisso (osimertinib)
    12ms
    Report of selpercatinib + osimertinib for #EGFR mt NSCLC with #RET mediated resistance to osimertinib @CCR_AACR. In 14pts, RR 50%, DCR 83%, median treatment duration 7.9m, tolerable profile. Resistance included RET G810S, EGFR C797S, and off-target bypass. https://t.co/jaX1ylRlIm (@StephenVLiu)
    EGFR (Epidermal growth factor receptor)
    |
    EGFR C797S
    |
    Tagrisso (osimertinib) • Retevmo (selpercatinib)
    1year
    Brilliant talk this morning from #NSCLC #EGFR expert @RamalingamMD who is one of our favorites! Acquired resistance #MET; #C797S etc.; novel therapies including mutation-agnostic #patritumab deruxtecan, the #HER3-DXd #ADC; plasma/tissue tips re #SCLC and #LUSC conversion—a tour… https://t.co/y0O8xAxQGj (@Exon20Group)
    EGFR (Epidermal growth factor receptor) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3)
    |
    EGFR C797S • ERBB3 mutation
    |
    patritumab deruxtecan (U3-1402)
    1year
    #ELCC23 ⁦@ZPiotrowskaMD⁩ ⁦@MGHThoracicOnc⁩ takes us through acqd resistance to targeted tx, that can be: - on target (eg C797S in egfr) - off target (eg MET amplif, seen across targets) - via histologic transformtn (eg small cell, squamous) ⁦@myESMO⁩ #LCSM (@DrJNaidoo)
    EGFR (Epidermal growth factor receptor)
    |
    EGFR C797S
    over1year
    Promising efficacy of 4th generation EGFR TKI after 3 weeks in NSCLC pt EGFR L858R, T790M, C797S mutations in progression post gefitinib, osimertinib and amivantamab...to be continued @GustaveRoussy @CICThoraciques (@dplanchard)
    Clinical
    |
    EGFR (Epidermal growth factor receptor)
    |
    EGFR mutation • EGFR L858R • EGFR T790M • EGFR C797S
    |
    Tagrisso (osimertinib) • gefitinib • Rybrevant (amivantamab-vmjw)
    over1year
    C797S resistant mutation occurs in 12.5% of patients treated with first line osimertinib for EGFR mut NSCLC. Mostly appears after 1 yr of osi (MET amplification is predominant the first year). Population eligible to 4th gen EGFR inhibitors targeting C797S is limited. #WCLC2022 (@BenjaminBesseMD)
    Clinical
    |
    MET (MET proto-oncogene, receptor tyrosine kinase)
    |
    MET amplification • EGFR C797S
    |
    Tagrisso (osimertinib)
    2years
    #TTLC22 Dr. @politikaterina reviews acquired resistance to #EGFR TKIs. Similar mechanisms of resistance to osimertinib and 1G/2G TKIs but different frequencies. Interestingly, some resistance mutations seem allele specific - C797S more with del19 and L718 more in L858R. #LCSM (@StephenVLiu)
    EGFR (Epidermal growth factor receptor)
    |
    EGFR L858R • EGFR C797S
    |
    Tagrisso (osimertinib)
    over2years
    #WCLC21 Included 70pts with #EGFR and leptomeningeal carcinoma post osimertinib with cfDNA analysis done on CSF. 22/70 had a biomarker - including C797S, #MET amp, #ALK, #HER2 amp, #EGFR amp. Note the discordance between liquid cfDNA and CSF cfDNA analyses (most with CSF only mt) (@StephenVLiu)
    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • ALK (Anaplastic lymphoma kinase)
    |
    EGFR C797S
    |
    Tagrisso (osimertinib)
    over2years
    #WCLC21 Dr. JWT van der Wel presents data from paired tissue & liquid biopsies in 50 pts with #EGFR NSCLC post osimertinib. Many of the expected findings (MET, C797S, HER2) but notice the discordance (red plasma only, green tissue only, blue both). These tests are complementary! (@StephenVLiu)
    Clinical • Liquid biopsy
    |
    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2)
    |
    EGFR C797S
    |
    Tagrisso (osimertinib)
    almost3years
    Small sample size but interesting report in @JTOonline on 4 patients with de novo T790M/L858R #EGFR NSCLC with acquired resistance to osimertinib. Mechanisms of resistance identified: C797S, C797S/L798I, #MET amp and MTOR L1433S. #LCSM @IASLC @OncoAlert https://t.co/7mg1KB0n8H (@StephenVLiu)
    Clinical
    |
    EGFR (Epidermal growth factor receptor)
    |
    EGFR L858R • EGFR T790M • EGFR C797S
    |
    Tagrisso (osimertinib)
    3years
    #WCLC20 @IASLC @OncoAlert Efficacy of Patritumab-Dx in #EGFRMT #NSCLC. HER3 was expressed in nearly all tumors. Efficacy was observed in EGFR C797S, MET amplification, HER2 MT BRAF fusion, and PIK3CA MT. @HelenaYu923 @EGFRResisters (@CharuAggarwalMD)
    Clinical
    |
    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • BRAF (B-raf proto-oncogene) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • MET (MET proto-oncogene, receptor tyrosine kinase) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3)
    |
    HER-2 amplification • MET amplification • ERBB3 expression • EGFR C797S • BRAF fusion • BRAF amplification
    |
    patritumab (U3-1287)
    over3years
    Smart chemotherapies (ADC) appear as major players’ #ESMO20 (ie IMMU-132, etc). A HER3 directed ADC demonstrated a 25% ORR in heavily pretreated EGFR #lcsm (86% with osi, 90% CT, 40% PD(L)1) including EGFR C797S, MET ampl, HER2 mut, BRAF fusion, PI3K mut patients. ILD was 5.3%. (@jsoriamd)
    Clinical
    |
    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • BRAF (B-raf proto-oncogene) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3)
    |
    EGFR C797S • BRAF fusion
    |
    Trodelvy (sacituzumab govitecan-hziy)
    over3years
    #ESMO20 In 49 evaluable patients, 1 CR, 13 confirmed PR, 3 unconfirmed PR. Most with some reduction. Activity seen across various TKI resistance mechanisms including C797S, MET, KRAS, HER2, BRAF. #LCSM @OncoAlert (@StephenVLiu)
    Clinical
    |
    HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene)
    |
    EGFR C797S
    over3years
    I look forward to clin data! Urgent need as many EGFR pts with this “triple mutation” now; but we do not expect to see T790M/C797S much longer in the future as osi replaces 1gen drugs 1L. We need C797S drugs that don’t require T790M as next step IMO @EGFRResisters #LCSM #ESMO20 (@LeciaSequist)
    Clinical
    |
    EGFR (Epidermal growth factor receptor)
    |
    EGFR T790M • EGFR C797S
    over3years
    #ESMO20 Poster 1296 shows preclinical data of BLU-945 @BlueprintMeds, a 4th generation #EGFR TKI that can overcome T790M/C797S. Highly selective with subnanomolar IC50 for T790M/C797S (vs > 700 at wild type) and more potent with gefitinib or osimertinib. Phase I in 2021. #LCSM (@StephenVLiu)
    P1 data
    |
    EGFR (Epidermal growth factor receptor)
    |
    EGFR T790M • EGFR C797S
    |
    Tagrisso (osimertinib) • gefitinib • tigozertinib (BLU-945)
    over3years
    Promising perspectives for EGFR mutant #lcsm #ESMO20 with 4th generation EGFR TKI that can block triple mutant EGFR/T790M/C797S (@jsoriamd)
    EGFR (Epidermal growth factor receptor)
    |
    EGFR mutation • EGFR T790M • EGFR C797S • EGFR mutation + EGFR T790M • EGFR mutation + EGFR T790M + EGFR C797S
    over3years
    No EGFR mutation on new biopsy. So could argue a second primary NSCLC. No other expected resistance to osi either (e.g. C797S). (@dhughesPharmD)
    EGFR (Epidermal growth factor receptor)
    |
    EGFR mutation • EGFR C797S
    almost4years
    #OncoAlert Online @ASCO_pubs is a helpful review of the evolving management of #EGFR #NSCLC post-osimertinib. Important mechanisms include C797S, #SCLC, #MET and other fusions. More to come - remains vitally important to biopsy and sequence at PD! #LCSM https://t.co/MelQbhASSq (@StephenVLiu)
    EGFR (Epidermal growth factor receptor)
    |
    EGFR C797S
    |
    Tagrisso (osimertinib)
    almost4years
    #OncoAlert Report on a ph I/II trial of first line osimertinib + gefitinib in #EGFR NSCLC by Dr. Rotow. Will prevention of 2nd site mutations T790M, L718Q, C797S seen in vitro translate to more benefit? Report on 27 patients shows feasibility (though 11% G3 diarrhea). #OncoAlert (@StephenVLiu)
    EGFR (Epidermal growth factor receptor)
    |
    EGFR C797S • EGFR L718Q
    |
    Tagrisso (osimertinib) • gefitinib
    almost4years
    #OncoAlert Great correlatives to complement this trial including ctDNA analysis. Persistent detectable EGFR ctDNA at 6 weeks had worse PFS than those who cleared (9.8m vs 16.2m) and worse OS. Authors also characterized resistance (C797S, L718Q, squamous transformation). #LCSM (@StephenVLiu)
    EGFR (Epidermal growth factor receptor)
    |
    EGFR C797S • EGFR L718Q