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BIOMARKER:

EGFR S768I

i
Other names: EGFR, ERBB, ERBB1, Epidermal growth factor receptor
Entrez ID:
11d
P1/2, N=177, Active, not recruiting, Novartis Pharmaceuticals | Completed --> Active, not recruiting | Trial completion date: Nov 2020 --> Jul 2025 | Trial primary completion date: Nov 2020 --> Jul 2025
Clinical • Enrollment closed • Trial completion date • Trial primary completion date • Combination therapy
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MET (MET proto-oncogene, receptor tyrosine kinase)
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EGFR mutation • EGFR L858R • EGFR exon 19 deletion • EGFR L861Q • EGFR G719X • EGFR S768I • EGFR T790M negative
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Tabrecta (capmatinib) • nazartinib (EGF816)
14d
In the subset who had progressed on osimertinib, afatinib also yielded a superior progression-free survival (6.2 mo) than non-afatinib therapies (1.0 mo, HR = 0.04, p = 0.005) and alternative EGFR TKIs (1.8 mo, HR = 0.06, p = 0.033). EGFR G724S emerges as a resistant mutation against EGFR TKI preferentially in the context of a rare variant of 19del, whereas it might mediate differential mechanisms in the context of exon 20 mutation. We also found that afatinib could be a potential therapeutic option for patients with NSCLC with G724S.
Clinical • Journal
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EGFR (Epidermal growth factor receptor) • MET (MET proto-oncogene, receptor tyrosine kinase)
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EGFR mutation • MET amplification • EGFR T790M • EGFR exon 19 deletion • EGFR exon 20 insertion • EGFR exon 21 mutation • EGFR S768I • EGFR exon 20 mutation • EGFR E746_S752delinsV • EGFR G724S • EGFR E746
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Gilotrif (afatinib) • Tagrisso (osimertinib)
15d
Clinical • New P3 trial
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EGFR (Epidermal growth factor receptor)
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EGFR mutation • EGFR L858R • EGFR exon 19 deletion • EGFR L861Q • EGFR G719S • EGFR S768I • EGFR G719A • EGFR G719C
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Avastin (bevacizumab) • erlotinib
22d
Our findings suggested that afatinib is effective in patients with uncommon mutations. Mechanisms of afatinib resistance vary and need further investigation.
Journal
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EGFR (Epidermal growth factor receptor)
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EGFR mutation • EGFR L858R • EGFR T790M • EGFR L861Q • EGFR G719X • EGFR S768I • EGFR L747P • EGFR A767_V769dup • EGFR H835L • EGFR L833V
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Gilotrif (afatinib)
25d
Afatinib (A) was the most frequently administered TKI in both groups (46% and 51% in group 1 and 3, respectively)...MPFS in group 1 was 3.8 months with erlotinib (E, 29%), 9.1 months with gefitinib (G, 16%) and 5.0 months with osimertinib (O, 10%, overall log rank 0.014]... This real-world dataset confirms that patients with uncommon (group 1) and very rare EGFR mutations (group 3) benefit from EGFR-TKIs compared to chemotherapy. The comparison between the TKIs needs to be interpreted with caution due to small sample size. Altogether, the group of very rare EGFR mutations needs to be fu nctionally characterized.
Retrospective data
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EGFR (Epidermal growth factor receptor)
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EGFR mutation • EGFR L858R • EGFR T790M • EGFR exon 19 deletion • EGFR L861Q • EGFR G719X • EGFR S768I
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erlotinib • Gilotrif (afatinib) • Tagrisso (osimertinib) • gefitinib
2ms
Methods In this non-interventional, global, multicenter, retrospective study (NCT04179890), existing medical or electronic health records were searched for consecutive patients with uncommon EGFR mutations (T790M, ex20ins, major uncommon [G719X, L861Q or S768I], ‘other’, or compound mutations) who were EGFR TKI-naïve at diagnosis, treated with erlotinib, gefitinib, afatinib, osimertinib, or other systemic therapy. Optimal treatment requires improvements in pathology reports, with more emphasis on implementation of NGS methodology and precise definition of mutations. Patients treated with afatinib Median TTF, months Median OS, months ORR, % Median DoR, months All (n=132) Major uncommon (n=94) Compound (n=46) Other (n=9) Ex20ins (n=18) 11.3 14.3 12.6 10.8 8.3 24.5 24.5 23.4 20.2 22.5 43.8 50.6 52.5 28.6 18.8 12.0 12.0 10.0 10.5 5.5 Patients treated with first-generation EGFR TKI All (n=106) Major uncommon (n=80) Compound (n=32) Other (n=12) Ex20ins (n=10) 8.8 9.8 12.4 7.3 5.2 24.2 28.5 31.3 12.8 21.0 44.1 47.3 43.8 55.6 16.7 6.0 6.5 6.0 4.5 3.0
Clinical
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EGFR (Epidermal growth factor receptor)
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EGFR mutation • EGFR L858R • EGFR T790M • EGFR L861Q • EGFR G719X • EGFR S768I
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erlotinib • Gilotrif (afatinib) • Tagrisso (osimertinib) • gefitinib
3ms
Afatinib was tolerable with no new safety signals. Afatinib demonstrated encouraging efficacy in a broad patient population, including those with brain metastases or uncommon EGFR mutations.
P3 data • Retrospective data • Journal
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EGFR (Epidermal growth factor receptor)
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EGFR mutation • EGFR T790M • EGFR L861Q • EGFR G719X • EGFR S768I
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Gilotrif (afatinib)
3ms
15 pts with known acquired EGFR resistance mutations to osimertinib (osi; G724S, L718X, C797S) were given afa post osi: ORR: 36%. Afa showed activity against major uncommon, compound, other (including E709X and L747X) and some specific ex20ins mutations. Afa showed activity against major uncommon, compound, other (including E709X and L747X) and some specific ex20ins mutations. The data support the use of afa in these settings. Moderate activity was seen post-osi.
Clinical
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EGFR (Epidermal growth factor receptor)
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EGFR mutation • EGFR L858R • EGFR T790M • EGFR C797S • EGFR L861Q • EGFR G719X • EGFR S768I • EGFR G724S
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Gilotrif (afatinib) • Tagrisso (osimertinib)
3ms
Background: Despite being an established treatment (tx) option in pts with EGFR mutation-positive NSCLC with common mutations (Del19 or L858R), limited data exist for EGFR TKI tx in the 7–23% of pts with uncommon EGFR mutations. In this non-interventional, global study (NCT04179890), existing medical/electronic records were searched for consecutive EGFR TKI-naïve (at diagnosis) pts with uncommon EGFR mutations (major uncommon [G719X, L861Q or S768I], compound, ‘other’, ex20ins), treated with erlotinib, gefitinib, afatinib, osimertinib (1st- or 2nd-line). In a real-world setting, EGFR TKIs were the tx of choice in pts with uncommon EGFR mutations. ECOG PS remained stable in pts from 1st- to 2nd-line tx. Activity was highest in compound and major uncommon groups (including pts with poor risk factors).
Clinical • Real-world evidence
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EGFR (Epidermal growth factor receptor)
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EGFR mutation • EGFR L858R • EGFR L861Q • EGFR G719X • EGFR S768I
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erlotinib • Gilotrif (afatinib) • Tagrisso (osimertinib) • gefitinib
3ms
Clinical • New P3 trial
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EGFR (Epidermal growth factor receptor)
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EGFR mutation • EGFR L861Q • EGFR G719X • EGFR S768I
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Ameile (almonertinib)
4ms
P2, N=37, Recruiting, Duke University | Trial completion date: Jun 2023 --> Jun 2024 | Trial primary completion date: Jun 2021 --> Jun 2022
Clinical • Trial completion date • Trial primary completion date
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EGFR (Epidermal growth factor receptor)
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EGFR mutation • EGFR exon 20 insertion • EGFR L861Q • EGFR G719X • EGFR S768I • EGFR exon 20 mutation
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Tagrisso (osimertinib)
4ms
Clinical • New trial
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EGFR (Epidermal growth factor receptor)
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EGFR mutation • EGFR L858R • EGFR L861Q • EGFR G719X • EGFR S768I
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Gilotrif (afatinib) • Tagrisso (osimertinib)
4ms
Although phenotypically similar to patients with common EGFR mutations, patients with EGFR ex20-mut had worse survival, perhaps due to the lack of targeted therapies. Chemotherapy was superior to conventional EGFR TKIs in patients with EGFR ex20-ins, although there was moderate activity of TKIs in S768I mutations. ICIm was ineffective.
Clinical • Journal • IO biomarker • EGFR exon 20
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EGFR (Epidermal growth factor receptor)
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EGFR mutation • EGFR T790M • EGFR exon 20 insertion • EGFR S768I • EGFR exon 20 mutation
5ms
The chi-square including the covariates was 14.85 (P<0.01). Conclusion Our data indicated that EGFR uncommon mutations were widely distributed in Brazilian patients with NSCLC and may contribute to new perspectives on precision treatment.
Clinical
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EGFR (Epidermal growth factor receptor)
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EGFR mutation • EGFR L858R • EGFR exon 19 deletion • EGFR S768I • EGFR exon 18 mutation • EGFR G719C • EGFR A750P
5ms
The chi-square including the covariates was 14.85 (P<0.01). Conclusion Our data indicated that EGFR uncommon mutations were widely distributed in Brazilian patients with NSCLC and may contribute to new perspectives on precision treatment.
Clinical
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EGFR (Epidermal growth factor receptor)
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EGFR mutation • EGFR L858R • EGFR exon 19 deletion • EGFR S768I • EGFR exon 18 mutation • EGFR G719C • EGFR A750P
5ms
The chi-square including the covariates was 14.85 (P<0.01). Conclusion Our data indicated that EGFR uncommon mutations were widely distributed in Brazilian patients with NSCLC and may contribute to new perspectives on precision treatment.
Clinical
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EGFR (Epidermal growth factor receptor)
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EGFR mutation • EGFR L858R • EGFR exon 19 deletion • EGFR S768I • EGFR exon 18 mutation • EGFR G719C • EGFR A750P
5ms
The chi-square including the covariates was 14.85 (P<0.01). Conclusion Our data indicated that EGFR uncommon mutations were widely distributed in Brazilian patients with NSCLC and may contribute to new perspectives on precision treatment.
Clinical
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EGFR (Epidermal growth factor receptor)
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EGFR mutation • EGFR L858R • EGFR exon 19 deletion • EGFR S768I • EGFR exon 18 mutation • EGFR G719C • EGFR A750P
5ms
First-line afatinib is beneficial for Vietnamese patients with advanced EGFR-mutant NSCLC with a good response rate and prolonged TTF with manageable adverse event profile. Baseline brain metastasis status and starting doses do not significantly impact TTF.
Clinical • Journal
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EGFR (Epidermal growth factor receptor)
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EGFR mutation • EGFR L858R • EGFR L861Q • EGFR G719X • EGFR S768I
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Gilotrif (afatinib)
5ms
P1/2, N=395, Recruiting, Millennium Pharmaceuticals, Inc. | Trial primary completion date: May 2020 --> Mar 2022
Clinical • Trial primary completion date
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EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2)
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EGFR mutation • EGFR L858R • EGFR T790M • EGFR exon 19 deletion • EGFR exon 20 insertion • EGFR L861Q • HER-2 exon 20 insertion • EGFR G719X • EGFR S768I • EGFR exon 20 mutation • EGFR L861R
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carboplatin • pemetrexed • Exkivity (mobocertinib)
5ms
P1, N=38, Recruiting, Collin Blakely | Trial completion date: Sep 2024 --> May 2023 | Trial primary completion date: Sep 2022 --> May 2023
Trial completion date • Trial primary completion date • Combination therapy
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EGFR (Epidermal growth factor receptor) • TPX2 (TPX2 Microtubule Nucleation Factor)
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EGFR mutation • EGFR L858R • EGFR T790M • EGFR exon 19 deletion • EGFR L861Q • EGFR G719X • EGFR S768I • EGFR E709K • EGFR exon 19 insertion • EGFR V834L
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Tagrisso (osimertinib) • alisertib (MLN8237)
5ms
Clinical • Journal
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EGFR (Epidermal growth factor receptor)
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EGFR mutation • EGFR S768I • EGFR G719C • EGFR G719C + S768I
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Gilotrif (afatinib)
6ms
Patients with NSCLC in Qujing displayed a unique profile of driver gene mutations, especially a higher prevalence of EGFR compound mutations and dominant KRAS G12C subtype, in this study, indicating a peculiar etiology of NSCLC in Qujing. Therefore, a different paradigm of therapeutic strategy might need to be considered for patients with NSCLC in Qujing.
Clinical • Journal
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EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • BRAF (B-raf proto-oncogene) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • NRAS (Neuroblastoma RAS viral oncogene homolog) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
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KRAS mutation • EGFR mutation • KRAS G12C • EGFR L861Q • EGFR G719X • EGFR S768I • KRAS G12
6ms
Funding: Foundation Medicine Background: The emergence of osimertinib (osi) as standard of care therapy for EGFR-mutant NSCLC has led to investigations into understanding and overcoming drug resistance... Osi resistance in EGFR-mutant NSCLC is a poor prognosis condition . EGFR C797S is a recurring resistance mut which, in a minority of cases, can co-occur with alternate on and off target resistance muts detected with tissue and liquid biopsy.
IO biomarker
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EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • BRAF (B-raf proto-oncogene) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • RET (Ret Proto-Oncogene) • FGFR3 (Fibroblast growth factor receptor 3) • TACC3 (Transforming acidic coiled-coil containing protein 3) • STRN (Striatin) • CCDC6 (Coiled-Coil Domain Containing 6)
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BRAF V600E • EGFR mutation • HER-2 amplification • BRAF V600 • EGFR L858R • EGFR T790M • EGFR exon 19 deletion • RET fusion • ALK fusion • FGFR3-TACC3 fusion • EGFR C797S • CCDC6-RET fusion • EGFR S768I • BRAF fusion • EGFR G719A • FGFR3 fusion • EGFR G724S • STRN-ALK fusion • EGFR L718Q • EGFR G796S
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Tagrisso (osimertinib)
6ms
Follow-up data after EGFR-TKI (Erlotinib, Gefitinib, Afatinib and Osimertinib), chemotherapy and/or mono-PD(L)1 blockade was available for 252 patients . This real-world dataset confirms that patients with group 1(uncommon) EGFR mutations benefit from EGFR-TKIs and indicates that mono-anti PD(L)1 blockade is not superior to chemotherapy . Furthermore, patients with very rare EGFR mutations (group 3) also experienced a PFS benefit from EGFR-TKI compared to chemotherapy while immune therapy was not beneficial.
Clinical
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EGFR (Epidermal growth factor receptor)
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EGFR mutation • EGFR L858R • EGFR T790M • EGFR exon 19 deletion • EGFR L861Q • EGFR G719X • EGFR S768I
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erlotinib • Gilotrif (afatinib) • Tagrisso (osimertinib) • gefitinib
6ms
In the ongoing CHRYSALIS phase 1 study (NCT02609776), preliminary antitumor activity has been demonstrated with the combination of lazertinib and amivantamab in patients with treatment-naïve and osimertinib-relapsed EGFRm NSCLC (Cho Ann Oncol 2020;31:S813) . Blood samples will be collected to access PK . Tumor response will be assessed every 6 weeks by the investigator using RECIST, v1.1.
Clinical • P1 data • Combination therapy
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EGFR (Epidermal growth factor receptor) • MET (MET proto-oncogene, receptor tyrosine kinase)
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EGFR mutation • EGFR T790M • EGFR exon 20 insertion • EGFR L861Q • MET mutation • EGFR G719X • EGFR S768I • EGFR exon 20 mutation
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Tagrisso (osimertinib) • Rybrevant (amivantamab-vmjw) • Leclaza (lazertinib)
6ms
In this non-interventional, global, multi-center study (NCT04179890), existing medical or electronic health records were identified for consecutive EGFR TKI-naïve pts with uncommon EGFR mutations (T790M, ex20ins, major uncommon [G719X, L861Q or S768I], ‘other’ or compound mutations) treated with erlotinib, gefitinib, afatinib, osimertinib or other systemic therapy . In a real-world setting, EGFR TKIs were the preferred tx option in pts with uncommon EGFR mutations; strongest outcomes were seen in major uncommon and compound mutations, and in pts treated with afatinib . Data were in line with recent analyses of afatinib in uncommon mutations . Tx with an EGFR TKI should be considered as standard for most pts with uncommon mutations .
Clinical • Real-world evidence
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EGFR (Epidermal growth factor receptor)
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EGFR mutation • EGFR L858R • EGFR T790M • EGFR L861Q • EGFR G719X • EGFR S768I
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erlotinib • Gilotrif (afatinib) • Tagrisso (osimertinib) • gefitinib
6ms
Our data indicates that patients from Xuanwei with NSCLC harbouring G719X/S768I co-mutations may benefit from treatment with EGFR-tyrosine kinase inhibitors. Our comprehensive molecular profiling revealed unique genomic features of patients from Xuanwei with NSCLC, highlighting the potential for improvement in targeted therapy and immunotherapy.
Clinical • Journal • Next-generation sequencing • Tumor Mutational Burden • IO biomarker
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EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • TMB (Tumor Mutational Burden)
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KRAS mutation • EGFR mutation • TMB-H • EGFR L858R • EGFR T790M • EGFR exon 19 deletion • EGFR G719X • EGFR S768I
7ms
P2, N=170, Recruiting, Fondazione Ricerca Traslazionale
Clinical • New P2 trial
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EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
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EGFR mutation • BRAF mutation • EGFR L858R • EGFR T790M • EGFR exon 19 deletion • ALK rearrangement • EGFR L861Q • ALK mutation • MET mutation • ROS1 rearrangement • EGFR G719S • EGFR S768I • EGFR G719A • EGFR G719C
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Tagrisso (osimertinib) • Vizimpro (dacomitinib)
7ms
NSCLC patients in Qujing displayed a unique profile of drive gene mutations which indicated putative etiology of NSCLC in this area.
Clinical
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EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • BRAF (B-raf proto-oncogene) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • NRAS (Neuroblastoma RAS viral oncogene homolog) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
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KRAS mutation • EGFR mutation • KRAS G12C • EGFR L861Q • EGFR G719X • EGFR S768I • KRAS G12
7ms
Clinical • New P2 trial • IO biomarker
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BRAF (B-raf proto-oncogene) • PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase)
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KRAS mutation • EGFR mutation • BRAF mutation • EGFR T790M • EGFR L861Q • EGFR G719X • EGFR S768I
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Focus V (anlotinib) • Tyvyt (sintilimab)
8ms
The current study represents the first epidemiological study in Iraq to find EGFR mutations frequency among NSCLC patients that reveals the incidence rate of 27.53%, which is between the higher prevalence rate in Asian populations and lower rates in western countries. These results explain the genetic differences of NSCLC in the world due to ethnic differences of the population, more studies are needed in Arab countries to study the EGFR mutations, find the effect of ethnicity and environmental factors for lung cancer, and the subsequent therapy.
Clinical • Journal
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ALK (Anaplastic lymphoma kinase)
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EGFR mutation • EGFR L858R • EGFR T790M • EGFR exon 19 deletion • EGFR L861Q • ALK mutation • EGFR G719X • EGFR G719S • EGFR S768I • EGFR exon 18 mutation • EGFR G719A • EGFR G719C • EGFR positive
8ms
Clinical • New P2 trial
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EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • BRAF (B-raf proto-oncogene) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • PIAS4 (Protein Inhibitor Of Activated STAT 4)
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KRAS mutation • EGFR mutation • BRAF mutation • EGFR L858R • EGFR T790M • EGFR exon 19 deletion • ALK rearrangement • EGFR L861Q • ALK mutation • MET mutation • ROS1 rearrangement • EGFR G719S • EGFR S768I • EGFR exon 18 mutation • ROS1 mutation • EGFR G719A • EGFR G719C
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Vizimpro (dacomitinib)
8ms
Loperamide prophylaxis (first 8 weeks) was mandatory. Meaningful neratinib activity, regardless of single or complex G719X mutation, was seen in TKI-pretreated NSCLC patients with EGFR exon 18 mutations. ORR and mPFS appear better than previously reported for other EGFR TKIs in TKIrefractory patients. The neratinib SUMMIT trial continues to enroll EGFR exon 18-mutant NSCLC patients.
Clinical • Pan tumor
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EGFR (Epidermal growth factor receptor)
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EGFR mutation • EGFR T790M • EGFR G719X • EGFR S768I • EGFR exon 18 mutation • EGFR E709_T710delinsD • EGFR delE709_T710insD
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Nerlynx (neratinib) • loperamide
8ms
P3, N=200, Terminated, Sichuan Provincial People's Hospital | Trial completion date: Dec 2023 --> Aug 2020 | Recruiting --> Terminated | Trial primary completion date: Dec 2021 --> Aug 2020; After interim analysis, IRB recommend termination.
Trial completion date • Trial termination • Trial primary completion date
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EGFR (Epidermal growth factor receptor)
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EGFR mutation • EGFR L858R • EGFR exon 19 deletion • EGFR L861Q • EGFR S768I • EGFR G719A • EGFR exon 19 insertion
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erlotinib • gefitinib
9ms
For six patients, longitudinal data were analyzed and it was found that the ddPCR results reflected well the course of the disease and radiologic response. This study confirms that ddPCR on cfDNA supports the diagnosis and therapy selection, and shows that ddPCR multiplex assays on cfDNA could be a valuable additional diagnostic tool for therapy monitoring of NSCLC patients.
Clinical • Journal
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EGFR (Epidermal growth factor receptor)
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EGFR mutation • EGFR L858R • EGFR T790M • EGFR exon 19 deletion • EGFR C797S • EGFR L861Q • EGFR G719S • EGFR S768I • EGFR positive
9ms
Afatinib has clinical activity in NSCLC against major uncommon and compound EGFR mutations. It also has broad activity against other uncommon EGFR mutations and some exon 20 insertions. The data support the use of afatinib in these settings.
Clinical • Journal
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EGFR (Epidermal growth factor receptor)
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EGFR mutation • EGFR T790M • EGFR exon 20 insertion • EGFR L861Q • EGFR G719X • EGFR S768I
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Gilotrif (afatinib)
9ms
P2, N=30, Recruiting, Shanghai Chest Hospital | Not yet recruiting --> Recruiting
Clinical • Enrollment open
|
EGFR (Epidermal growth factor receptor)
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EGFR mutation • EGFR L858R • EGFR T790M • EGFR exon 19 deletion • EGFR L861Q • EGFR G719X • EGFR S768I • EGFR L747P • EGFR exon 18 mutation • EGFR G719A • EGFR T854A • EGFR D761Y • EGFR E709Q • EGFR E746 • EGFR I744_K745insKIPVAI • EGFR L747S • EGFR L861R • EGFR R776H • EGFR G779C • EGFR R776C
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Vizimpro (dacomitinib)
10ms
P1/2, N=331, Recruiting, Millennium Pharmaceuticals, Inc. | Active, not recruiting --> Recruiting
Clinical • Enrollment open
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EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2)
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EGFR mutation • EGFR L858R • EGFR T790M • EGFR exon 19 deletion • EGFR exon 20 insertion • EGFR L861Q • HER-2 exon 20 insertion • EGFR G719X • EGFR S768I • EGFR exon 20 mutation • EGFR L861R
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carboplatin • pemetrexed • Exkivity (mobocertinib)
10ms
Results EGFR G724S was identified from 2 patients prior to the administration of any treatment, (baseline) from 1 patient after gefitinib failure and from 5 patients after osimertinib failure. Conclusion Our study provides clinical evidence that afatinib monotherapy could be a potential therapeutic option for NSCLC patients with EGFR G724S. Further studies for evaluating the efficacy of afatinib in advanced NSCLC patients harboring EGFR G724S and the underlying resistance mechanism are warranted.
Clinical
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EGFR (Epidermal growth factor receptor) • BRAF (B-raf proto-oncogene)
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BRAF V600E • EGFR mutation • BRAF V600 • EGFR T790M • EGFR exon 19 deletion • EGFR exon 20 insertion • EGFR C797S • EGFR S768I • EGFR exon 18 mutation • EGFR exon 20 mutation • EGFR E746_S752delinsV • EGFR G724S • EGFR E746
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Gilotrif (afatinib) • Tagrisso (osimertinib) • gefitinib
10ms
Our study contributes an incremental step in understanding the clinical responses of patients with rare EGFR mutations located in exon 18 and 19. Understanding the treatment responses and survival outcomes are critical in the optimal treatment management and improving the survival outcomes of patients with rare EGFR mutations.
Clinical
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EGFR (Epidermal growth factor receptor)
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EGFR mutation • EGFR L858R • EGFR T790M • EGFR exon 19 deletion • EGFR L861Q • EGFR G719X • EGFR S768I • EGFR L747P • EGFR exon 18 mutation • EGFR E746 • EGFR L861R
10ms
Conclusion More and more uncommon EGFR mutations are identified owing to the development of NGS. This is the largest NGS-based cohort of Chinese lung cancers for investigating uncommon EGFR mutations, and 5.48% patients that with EGFR-TKI-sensitive uncommon mutations alone were found, which should be informative for the clinical therapies.
Clinical
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EGFR (Epidermal growth factor receptor)
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EGFR mutation • EGFR L861Q • EGFR G719X • EGFR G719S • EGFR S768I • EGFR exon 18 mutation • EGFR G719C • EGFR A750P • EGFR E746 • EGFR L747_P753delinsS
10ms
Results Among 45 patients included (median age 65 yrs; female 62%; ECOG 0-1 84%), most frequent EGFR-TKI used was afatinib (n=23), followed by erlotinib/gefitinib (n=13), and osimertinib (n=9). Considerable clinical activity was observed to first-line EGFR-TKI in our study. Patients with complex mutations had significantly better survival.
Clinical • Real-World Evidence
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EGFR (Epidermal growth factor receptor)
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EGFR mutation • EGFR L858R • EGFR T790M • EGFR exon 19 deletion • EGFR exon 20 insertion • EGFR L861Q • EGFR G719X • EGFR S768I • EGFR exon 18 mutation • EGFR exon 20 mutation
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erlotinib • Gilotrif (afatinib) • Tagrisso (osimertinib) • gefitinib
10ms
Conclusion Osimertinib is an effective first-line treatment in Asian patients with advanced EGFRm+ NSCLC with durable OS, PFS and TTF. Despite good responses in patients with baseline BM and exon 21 mutation, additional treatment strategies are needed to improve their CNS outcomes.
Clinical • PD(L)-1 Biomarker • IO biomarker
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EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1) • ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
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EGFR mutation • EGFR T790M • EGFR exon 19 deletion • EGFR exon 21 mutation • RET rearrangement • EGFR S768I
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Tagrisso (osimertinib)
10ms
Patients received mandatory diarrhea prophylaxis with loperamide (first 6 weeks, then PRN). The ORR and mPFS appeared better than reported in the literature for other EGFR TKIs in TKI-refractory patients. Further evaluation of neratinib in patients with NSCLC and this uncommon EGFR mutation is ongoing.
Pan tumor
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EGFR (Epidermal growth factor receptor)
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EGFR mutation • EGFR T790M • EGFR G719X • EGFR S768I • EGFR exon 18 mutation
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Nerlynx (neratinib) • loperamide
10ms
Conclusion We performed a real-world data analysis of PD-L1 expression and its correlation with driver mutations in Chinese cancer patients. Such results will give insights into prevalence of PD-L1 higher expression, driver mutations and their associations in NSCLC immune-checkpoint inhibitor treatment.
Real-world evidence • Clinical • PD(L)-1 Biomarker • IO biomarker
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EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase)
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PD-L1 expression • KRAS mutation • EGFR mutation • PD-L1 overexpression • EGFR L858R • EGFR T790M • EGFR exon 19 deletion • EGFR expression • EGFR exon 20 insertion • PD-L1 negative • EGFR L861Q • EGFR G719X • EGFR S768I • KRAS expression
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PD-L1 IHC 22C3 pharmDx
10ms
The mutation rates of G719X, G719X+ L861Q, G719X+ S768I and S768I are higher in Xuanwei patients than those in non-Xuanwei patients. The combined mutation rate of G719X and L861Q in Han nationality is higher than that of ethnic minorities.
Clinical • Journal
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EGFR (Epidermal growth factor receptor)
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EGFR mutation • EGFR L858R • EGFR L861Q • EGFR G719X • EGFR S768I
10ms
A higher allele frequency of EGFR mutations, particularly EGFR-activating mutations, in plasma ctDNA is a poor prognostic marker. Further studies on the clinical utility of liquid biopsy are needed.
Clinical • Journal
|
EGFR (Epidermal growth factor receptor)
|
EGFR mutation • EGFR L858R • EGFR T790M • EGFR L861Q • EGFR S768I • EGFR positive
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Tagrisso (osimertinib)
11ms
In LUX-Lung 7, a head-to-head phase IIb trial, afatinib improved progression-free survival and time-to-treatment failure versus the first-generation reversible EGFR tyrosine kinase inhibitor, gefitinib, albeit with a higher incidence of serious treatment-related adverse events. In this review, we provide a detailed overview of the pharmacology, efficacy, and safety of afatinib, discuss treatment sequencing strategies following emergence of different resistance mechanisms, and shed light on the economic impact of afatinib. We also provide a comparison of afatinib with the available EGFR tyrosine kinase inhibitors and discuss its position within treatment strategies for patients with EGFRm+ NSCLC.
Clinical • Journal
|
EGFR (Epidermal growth factor receptor)
|
EGFR mutation • EGFR L858R • EGFR L861Q • EGFR G719X • EGFR S768I
|
Gilotrif (afatinib) • gefitinib
11ms
The results highlight the distinct EGFR mutation spectrum of NSCLC patients in Xuanwei region compared with other regions, with higher uncommon mutations but lower common mutations. The distinct Xuanwei featured genetic variations provide a unique model to further study carcinogenesis of lung cancer.
Retrospective data • Review
|
EGFR (Epidermal growth factor receptor)
|
EGFR mutation • EGFR L858R • EGFR G719X • EGFR S768I • EGFR exon 18 mutation
11ms
Overall TAT for the ultra-rapid workflow was reduced by ~50% compared to PCR/CE, and in most cases, results are delivered on the same day as tumor sampling. The lack of nucleic acid extraction and single-slide sample input enables targeted profiling of even scant tumor samples. Although both PCR/CE and the ultra-rapid workflow provide drastic improvement of TAT compared to NGS-based profiling, more comprehensive coverage of actionable EGFR mutations in the ultrarapid workflow allows for faster and more definitive treatment of NSCLC
Next-generation sequencing
|
EGFR (Epidermal growth factor receptor)
|
EGFR mutation • EGFR L858R • EGFR T790M • EGFR exon 19 deletion • EGFR L861Q • EGFR G719S • EGFR S768I • EGFR exon 18 mutation • EGFR G719A • EGFR G719C
|
Idylla™ EGFR Mutation Test
11ms
Combination of dabrafenib and trametinib was potent against a rare BRAF K601E mutation. Afatinib was the most potent EGFR-TKI against uncommon EGFR mutations including L861Q, G719C/S768I, and D770_N771insG. Aurora kinase A (AURKA) was identified as a novel resistance mechanism to olmutinib, a mutant-selective, third-generation EGFR-TKI, and inhibition of AURKA overcame the resistance. We presented an efficient protocol for establishing PDCs. PDCs empowered precision medicine with promising translational values.
Clinical • Journal
|
EGFR (Epidermal growth factor receptor) • BRAF (B-raf proto-oncogene) • AURKA (Aurora kinase A)
|
EGFR mutation • BRAF mutation • EGFR L861Q • EGFR S768I • BRAF K601E • EGFR G719C • BRAF K601
|
Mekinist (trametinib) • Gilotrif (afatinib) • Tafinlar (dabrafenib) • Olita (olmutinib)
11ms
Subgroup analysis showed that ALK (p < 0.001) and ROS1 (p < 0.05) fusions and rare EGFR mutations (p < 0.001) were associated with non-Han ethnic patients. Yunnan NSCLC patients from Xuanwei and non-Han ethnic patients had an obviously unique prevalence of GAs.
Journal
|
EGFR (Epidermal growth factor receptor) • BRAF (B-raf proto-oncogene) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
|
KRAS mutation • EGFR mutation • BRAF mutation • EGFR exon 19 deletion • ALK fusion • ROS1 fusion • EGFR G719X • EGFR S768I • EGFR mutation + KRAS mutation • ALK-ROS1 fusion
11ms
P3, N=200, Recruiting, Sichuan Provincial People's Hospital | Trial completion date: Dec 2021 --> Dec 2023 | Trial primary completion date: Dec 2020 --> Dec 2021
Trial completion date • Trial primary completion date
|
EGFR (Epidermal growth factor receptor)
|
EGFR mutation • EGFR L858R • EGFR exon 19 deletion • EGFR L861Q • EGFR S768I • EGFR G719A • EGFR exon 19 insertion
|
erlotinib • gefitinib
11ms
P3, N=300, Recruiting, National Cancer Institute (NCI) | Not yet recruiting --> Recruiting
Clinical • Enrollment open
|
EGFR (Epidermal growth factor receptor)
|
EGFR mutation • EGFR L858R • EGFR exon 20 insertion • EGFR L861Q • EGFR G719X • EGFR S768I • EGFR exon 20 mutation
|
Avastin (bevacizumab) • Tagrisso (osimertinib)
12ms
No intra- or intertumor heterogeneity was observed for EGFR compound mutations. Our results indicate that both EGFR mutations were truncal and selective elimination of cancer cells with uncommon EGFR mutations is unrealistic.
Clinical • Journal
|
EGFR (Epidermal growth factor receptor) • TERT (Telomerase Reverse Transcriptase)
|
EGFR mutation • EGFR L858R • EGFR G719X • EGFR S768I • EGFR G719A • EGFR G719X + S768I • EGFR E709G • EGFR G719A + S768I • EGFR L858R + R776H • EGFR L858R + S768I
1year
Clinical • Trial completion • Combination therapy
|
MET (MET proto-oncogene, receptor tyrosine kinase)
|
EGFR mutation • EGFR L858R • EGFR exon 19 deletion • EGFR L861Q • EGFR G719X • EGFR S768I • EGFR T790M negative
|
Tabrecta (capmatinib) • nazartinib (EGF816)
1year
Uncommon mutations were classed as: de novo T790M; exon 20 insertions (Ins20); major uncommon mutations (G719X/L861Q/S768I); compound mutations (≥2 uncommon mutations); and other uncommon mutations. Legal entity responsible for the study: Boehringer Ingelheim. Funding: Boehringer Ingelheim.
Clinical
|
EGFR (Epidermal growth factor receptor)
|
EGFR mutation • EGFR T790M • EGFR L861Q • EGFR G719X • EGFR S768I
|
Gilotrif (afatinib) • MK-6302 (pegfilgrastim biosimilar)
1year
Uncommon mutations were classed as: de novo T790M; exon 20 insertions (Ins20); major uncommon mutations (G719X/L861Q/S768I); compound mutations (≥2 uncommon mutations); and other uncommon mutations. Yang JC, et al. Lancet Oncol 2015;16:830‒8 Boehringer Ingelheim.
Clinical
|
EGFR (Epidermal growth factor receptor)
|
EGFR mutation • EGFR T790M • EGFR L861Q • EGFR G719X • EGFR S768I
|
Gilotrif (afatinib) • MK-6302 (pegfilgrastim biosimilar)
1year
Uncommon mutations were classed as: de novo T790M; exon 20 insertions (Ins20); major uncommon mutations (G719X/L861Q/S768I); compound mutations (≥2 uncommon mutations); and other uncommon mutations. Yang JC, et al. Lancet Oncol 2015;16:830‒8 Boehringer Ingelheim.
Clinical
|
EGFR (Epidermal growth factor receptor)
|
EGFR mutation • EGFR T790M • EGFR L861Q • EGFR G719X • EGFR S768I
|
Gilotrif (afatinib) • MK-6302 (pegfilgrastim biosimilar)
1year
P3, N=200, Recruiting, Sichuan Provincial People's Hospital | Trial completion date: Dec 2020 --> Dec 2021 | Trial primary completion date: Dec 2019 --> Dec 2020
Trial completion date • Trial primary completion date
|
EGFR (Epidermal growth factor receptor)
|
EGFR mutation • EGFR L858R • EGFR exon 19 deletion • EGFR L861Q • EGFR S768I • EGFR G719A • EGFR exon 19 insertion
|
erlotinib • gefitinib
1year
Afatinib is effective in pts with NSCLC with major uncommon and compound EGFR mutations, with broad activity against other uncommon EGFR mutations and some Ins20 mutations, unaffected by ethnicity. Asian pts appeared to have a high proportion of major uncommon mutations, known to be highly sensitive to afatinib.
Clinical
|
EGFR (Epidermal growth factor receptor)
|
EGFR mutation • EGFR T790M • EGFR L861Q • EGFR G719X • EGFR S768I • EGFR G719X + S768I • EGFR L861Q + G719X • EGFR mutation + EGFR T790M
|
Gilotrif (afatinib) • MK-6302 (pegfilgrastim biosimilar)
1year
Afatinib treatment at 40 mg daily is associated with high rates of adverse events and dose reductions; alternative strategies including pulse intermittent dosing should be evaluated prospectively. Osimertinib (with favorable safety profile and intracranial penetration) has shown promising results in this population in a phase II trial from South Korea; additional trials are ongoing.
Clinical • Journal
|
EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase)
|
KRAS mutation • EGFR mutation • EGFR L858R • EGFR T790M • EGFR exon 19 deletion • EGFR L861Q • EGFR L858R + T790M • EGFR G719X • EGFR S768I • EGFR T790M + exon 19 deletion • EGFR G719A • EGFR G719X + S768I • EGFR L861Q + G719X • EGFR T790M + KRAS mutation • EGFR mutation + EGFR T790M • EGFR G719A + S768I • EGFR L858R + EGFR exon 19 deletion • EGFR L858R + S768I • EGFR exon 19 deletion + EGFR S768I
|
Gilotrif (afatinib) • Tagrisso (osimertinib)
1year
Treatment with afatinib (40 mg/day) produced a partial response, which was maintained for 17 months with continued treatment. A literature review revealed that lung cancer with G719X/S768I compound mutation exhibited good response to EGFR-TKIs, even better than that of lung cancers with single uncommon mutations.
Clinical • Review • Journal
|
EGFR (Epidermal growth factor receptor)
|
EGFR mutation • EGFR L858R • EGFR exon 19 deletion • EGFR L861Q • EGFR G719X • EGFR S768I • EGFR G719X + S768I • EGFR L861Q + G719X • EGFR L858R + S768I • EGFR exon 19 deletion + EGFR S768I
|
Gilotrif (afatinib)
1year
We report osimertinib inhibits signalling pathways and cellular growth in G719X mutant cell lines in vitro and demonstrate sustained tumor growth inhibition of PDX harboring the G719X mutation alone or in combination with L861Q and S768I. Together this data supports clinical testing of osimertinib in patients with uncommon EGFR NSCLC.
Journal
|
EGFR (Epidermal growth factor receptor)
|
EGFR mutation • EGFR L858R • EGFR T790M • EGFR exon 20 insertion • EGFR L861Q • EGFR L858R + T790M • EGFR G719X • EGFR S768I • EGFR exon 20 mutation • EGFR G719X + S768I • EGFR L861Q + G719X • EGFR mutation + EGFR T790M • EGFR L858R + S768I
|
Tagrisso (osimertinib)
1year
Osimertinib demonstrated favorable activity with manageable toxicity in patients with NSCLC harboring uncommon EGFR mutations.
Clinical • P2 data • Journal
|
EGFR (Epidermal growth factor receptor)
|
EGFR mutation • EGFR L858R • EGFR T790M • EGFR exon 19 deletion • EGFR L861Q • EGFR L858R + T790M • EGFR G719X • EGFR S768I • EGFR T790M + exon 19 deletion • EGFR G719X + S768I • EGFR L861Q + G719X • EGFR mutation + EGFR T790M • EGFR L858R + EGFR exon 19 deletion • EGFR L858R + S768I • EGFR exon 19 deletion + EGFR S768I
|
Tagrisso (osimertinib)
1year
The shorter survival of patients with the S768I SNV predicts aggressive disease and poor prognosis as a result of this mutation. Studies in larger cohorts and/or animal models are necessary to confirm these findings.
Journal
|
EGFR (Epidermal growth factor receptor)
|
EGFR mutation • EGFR exon 19 deletion • EGFR S768I • EGFR exon 19 deletion + EGFR S768I
1year
P2, N=30, Not yet recruiting, Shanghai Chest Hospital
Clinical • New P2 trial
|
EGFR (Epidermal growth factor receptor)
|
EGFR mutation • EGFR L858R • EGFR T790M • EGFR exon 19 deletion • EGFR L861Q • EGFR G719X • EGFR S768I • EGFR L747P • EGFR exon 18 mutation • EGFR G719A • EGFR T854A • EGFR D761Y • EGFR E709Q • EGFR E746 • EGFR I744_K745insKIPVAI • EGFR L747S • EGFR L861R • EGFR R776H • EGFR G779C • EGFR R776C
|
Vizimpro (dacomitinib)
1year
Lung cancer and genetically engineered cell lines, as well as murine xenograft models were used to evaluate the efficacy of TAS6417 and other approved/in-development EGFR TKIs (erlotinib, afatinib, osimertinib, and poziotinib). Taken together, we demonstrate that TAS6417 is a potent EGFR TKI with a broad spectrum of activity and a wider therapeutic window than most approved/in-development generations of EGFR inhibitors. Implications: TAS6417/CLN-081 is a potent EGFR TKI with a wide therapeutic window and may be effective in lung cancer patients with clinically relevant EGFR mutations.
Journal
|
EGFR (Epidermal growth factor receptor)
|
EGFR mutation • EGFR L858R • EGFR T790M • EGFR exon 19 deletion • EGFR exon 20 insertion • EGFR L861Q • EGFR L858R + T790M • EGFR G719X • EGFR S768I • EGFR T790M + exon 19 deletion • EGFR exon 20 mutation • EGFR G719X + S768I • EGFR L861Q + G719X • EGFR L858R + EGFR exon 19 deletion • EGFR L858R + S768I • EGFR exon 19 deletion + EGFR S768I
|
erlotinib • Gilotrif (afatinib) • Tagrisso (osimertinib) • poziotinib (HM 78136B) • CLN-081
1year
Clinical
|
EGFR (Epidermal growth factor receptor)
|
EGFR mutation • EGFR T790M • EGFR L861Q • EGFR G719X • EGFR S768I • EGFR G719X + S768I • EGFR L861Q + G719X • EGFR mutation + EGFR T790M
|
Gilotrif (afatinib)
1year
Funding: Pfizer Pharma GmbH. Clinical trial identification: Study Number 2016/01.
Clinical
|
EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • BRAF (B-raf proto-oncogene) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
|
KRAS mutation • BRAF mutation • ROS1 fusion • EGFR S768I • EGFR mutation + KRAS mutation • EGFR G719C • ALK-ROS1 fusion • EGFR E746 • EGFR G719C + S768I
1year
Legal entity responsible for the study: Janssen Pharmaceutical companies of Johnson and Johnson. Funding: Janssen Pharmaceutical companies of Johnson and Johnson.
Clinical
|
EGFR (Epidermal growth factor receptor)
|
EGFR mutation • EGFR T790M • EGFR exon 20 insertion • EGFR S768I • EGFR exon 20 mutation • EGFR mutation + EGFR T790M
1year
Furthermore, patients with compound mutations had significantly poorer prognoses than that of cases of single EGFR mutations (p=0.043). Overall, clinicopathological features of common, uncommon, and compound EGFR mutations are similar; however, tumors with compound mutations may be characterized by aggressive behavior and histological findings of clear cell features.
Clinical • Journal
|
EGFR (Epidermal growth factor receptor) • NKX2-1 (NK2 Homeobox 1)
|
EGFR mutation • EGFR L858R • EGFR L858R + T790M • EGFR S768I • EGFR E709G • EGFR L858R + S768I
1year
P2, N=95, Recruiting, European Thoracic Oncology Platform | Not yet recruiting --> Recruiting
Clinical • Enrollment open • Preclinical • PD(L)-1 Biomarker
|
EGFR (Epidermal growth factor receptor)
|
EGFR mutation • EGFR L858R • EGFR T790M • EGFR G719X • EGFR S768I
|
Avastin (bevacizumab) • carboplatin • Tecentriq (atezolizumab) • paclitaxel • pemetrexed
over1year
P2, N=95, Not yet recruiting, European Thoracic Oncology Platform | Initiation date: Mar 2020 --> Jul 2020
Clinical • Preclinical • Trial initiation date • PD(L)-1 Biomarker
|
EGFR (Epidermal growth factor receptor)
|
EGFR mutation • EGFR L858R • EGFR T790M • EGFR G719X • EGFR S768I
|
Avastin (bevacizumab) • carboplatin • Tecentriq (atezolizumab) • paclitaxel • pemetrexed
over1year
P1/2, N=306, Active, not recruiting, Millennium Pharmaceuticals, Inc. | N=97 --> 306
Clinical • Enrollment change
|
EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2)
|
EGFR mutation • EGFR L858R • EGFR T790M • EGFR exon 19 deletion • EGFR exon 20 insertion • EGFR L861Q • HER-2 exon 20 insertion • EGFR G719X • EGFR S768I • EGFR exon 20 mutation • EGFR L861R
|
carboplatin • pemetrexed • Exkivity (mobocertinib)
over1year
After postoperative recurrence, the patient was treated with osimertinib, and an excellent and long-lasting clinical response was achieved. The patient has taken osimertinib for 31.0 months and exhibited a partial response, and her follow-up is ongoing.
Clinical • Journal
|
EGFR (Epidermal growth factor receptor)
|
EGFR mutation • EGFR G719X • EGFR S768I • EGFR G719X + S768I
|
Tagrisso (osimertinib)
over1year
In clinical practice, afatinib was active in patients with u-EGFRm NSCLC, particularly in complex and single mutations. Further strategies are needed for patients with ins20, a subgroup u-EGFRm with a lower clinical benefit with afatinib.
Retrospective data • Journal
|
EGFR (Epidermal growth factor receptor)
|
EGFR mutation • EGFR L858R • EGFR exon 20 insertion • EGFR L861Q • EGFR L858R + T790M • EGFR G719X • EGFR S768I • EGFR exon 20 mutation • EGFR L861Q + G719X
|
Gilotrif (afatinib) • MK-6302 (pegfilgrastim biosimilar)
over1year
There were marked differences between individuals regarding the efficacy of EGFR-TKI treatment and the survival time of patients with uncommon EGFR mutations, second-line EGFR-TKIs had a lower ORR and DCR while had a longer mPFS. All of these could provide a basis for the exploration of different regimens for patients with different types of uncommon mutations.
Clinical • Journal
|
EGFR (Epidermal growth factor receptor)
|
EGFR mutation • EGFR expression • EGFR L861Q • EGFR G719X • EGFR S768I • EGFR L861Q + G719X
over1year
"The disparity in the prevalence of hormone receptors in lung cancers affecting men and women deserves further exploration. The presence of hormone receptors in NSCLC is increased in women and in tumors bearing EGFR mutations. Further elucidation of the mechanism and dual targeting of EGFR and ER in patients with HR+ NSCLC deserves exploration."
EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • BRAF (B-raf proto-oncogene) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • ER (Estrogen receptor) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • PGR (Progesterone receptor)
|
TP53 mutation • KRAS mutation • EGFR mutation • HR positive • BRAF mutation • EGFR L858R • EGFR L861Q • EGFR G719X • EGFR S768I • ALK translocation • EGFR G719X + S768I • EGFR L861Q + G719X • EGFR L858R + S768I • ER expression
over1year
This study demonstrates that the function of tumor suppressor gene RB1 in advanced stage of NSCLC. From the results, we considered RB1 mutation had influence on bone metastases. Although loss-of-function mutations in tumor suppressor gene (TSG) RB1 always had no targets therapeutic drugs, it also suggested that some other clinically treatment can be performed as soon as possible.
TP53 (Tumor protein P53) • RB1 (RB Transcriptional Corepressor 1)
|
TP53 mutation • EGFR mutation • EGFR L858R • EGFR exon 20 insertion • EGFR L861Q • RB1 mutation • EGFR G719S • EGFR S768I • EGFR exon 20 mutation • EGFR G719S + L861Q • EGFR L858R + S768I
over1year
In this largest known clinically annotated dataset of patients with atypical EGFR-mutations treated with osi, activity was noted, though 1L clinical benefit on osi appears lower in this multicenter US cohort than in E19del or L858R. These results are comparable to the recently published prospective phase II trial (Cho et al, 2019) conducted in Korea. Patients with L861Q and Exon 19 insertion appeared to benefit the most from osi in this time on treatment retrospective analysis.
Retrospective data
|
EGFR (Epidermal growth factor receptor)
|
EGFR mutation • EGFR L858R • EGFR T790M • EGFR exon 20 insertion • EGFR L861Q • EGFR L858R + T790M • EGFR G719X • EGFR S768I • EGFR T790M + exon 19 deletion • EGFR G719X + S768I • EGFR L861Q + G719X
|
Tagrisso (osimertinib)
over1year
P1/2, N=177, Active, not recruiting, Novartis Pharmaceuticals | Trial primary completion date: Sep 2019 --> Jul 2020
Clinical • Trial primary completion date • Combination therapy
|
MET (MET proto-oncogene, receptor tyrosine kinase)
|
EGFR mutation • EGFR L858R • EGFR exon 19 deletion • EGFR L861Q • EGFR G719X • EGFR S768I • EGFR T790M negative
|
Tabrecta (capmatinib) • nazartinib (EGF816)
over1year
Other agents, such as dacomitinib, and new drug combinations, such as regimens including anti-angiogenic agents or chemotherapy, demonstrated to significantly prolong progression-free survival or overall survival, representing potential alternative to osimertinib. Many questions remain opened, including best drug sequencing and needing of new therapeutic approaches extending patient survival and cure rate.
Clinical • Journal
|
EGFR (Epidermal growth factor receptor)
|
EGFR mutation • EGFR exon 20 insertion • EGFR L861Q • EGFR G719X • EGFR S768I
|
Tagrisso (osimertinib) • Vizimpro (dacomitinib)
over1year
Clinical • Journal
|
EGFR (Epidermal growth factor receptor)
|
EGFR S768I
|
Tagrisso (osimertinib)
over1year
High rates of concomitant PD-L1 expression and CD8 + TILs within the tumor microenvironment were observed in NSCLC patients with uncommon EGFR mutations. Further investigations are needed to confirm the therapeutic sensitivity to PD-1 blockade in this subgroup.
Clinical • Journal • PD(L)-1 Biomarker
|
EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1) • CD8 (cluster of differentiation 8)
|
PD-L1 expression • EGFR mutation • EGFR L858R • EGFR expression • EGFR L861Q • EGFR G719X • EGFR S768I • TILs
over1year
High-sensitivity ASRP-based assays can overlook uncommon mutations. This detection failure rate is worth noting, especially when treating patients from regions known to have a high prevalence of EGFR mutation. Patients carrying uncommon mutations may still benefit from EGFR-TKI therapy.
Journal
|
EGFR (Epidermal growth factor receptor)
|
EGFR mutation • EGFR exon 19 deletion • EGFR L861Q • EGFR S768I
over1year
EGFR extracellular domain mutation, BCL2L11 loss, PI3K-AKT-mTOR signaling pathway (PTEN, PIK3CA mutations), MET amplification, ERBB2 amplification or MYC amplification might contribute to molecular mechanisms of primary resistance to icotinib in EGFR uncommon mutations NSCLC. Combined targeted therapy or chemotherapy should be considered in this population.
Clinical • Journal
|
EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog)
|
MET amplification • PTEN mutation • EGFR L861Q • EGFR G719X • EGFR S768I
|
Conmana (icotinib)
over1year
P1/2, N=97, Active, not recruiting, Millennium Pharmaceuticals, Inc. | Recruiting --> Active, not recruiting
Clinical • Enrollment closed
|
EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2)
|
EGFR mutation • EGFR L858R • EGFR T790M • EGFR exon 19 deletion • EGFR exon 20 insertion • EGFR L861Q • HER-2 exon 20 insertion • EGFR G719X • EGFR S768I • EGFR exon 20 mutation • EGFR L861R
|
carboplatin • pemetrexed • Exkivity (mobocertinib)
over1year
Clinical • New P2 trial • Preclinical • PD(L)-1 Biomarker
|
EGFR (Epidermal growth factor receptor)
|
EGFR mutation • EGFR L858R • EGFR T790M • EGFR G719X • EGFR S768I
|
Avastin (bevacizumab) • carboplatin • Tecentriq (atezolizumab) • paclitaxel • pemetrexed
over1year
P2, N=150, Recruiting, Spectrum Pharmaceuticals, Inc | Not yet recruiting --> Recruiting
Clinical • Enrollment open
|
EGFR (Epidermal growth factor receptor)
|
EGFR mutation • HER-2 amplification • EGFR L858R • EGFR T790M • HER-2 mutation • EGFR L861Q • HER-2 V777L • HER-2 exon 20 insertion • EGFR G719X • HER-2 S310F • EGFR S768I • EGFR E709K • HER-2 L869R • HER-2 V842I • EGFR P596L • EGFR R222C • HER-2 I655V • HER-2 T798M • EGFR E746 • HER-2 D769H • HER-2 R678Q • HER-2 T798I • HER-2 mutation + HER-2 T798I • EGFR V774M
|
poziotinib (HM 78136B)
over1year
Osimertinib, a 3rd-generation, irreversible, oral EGFR-tyrosine kinase inhibitor (TKI), potently and selectively inhibits both EGFR-TKI sensitising (EGFRm) and EGFR T790M mutations and has shown efficacy in the CNS... This analysis shows a high prevalence of EGFRm mutations in Asian and female pts with stage IB–IIIA NSCLC following complete resection, which is consistent with the advanced setting.
EGFR (Epidermal growth factor receptor)
|
EGFR mutation • EGFR L858R • EGFR T790M • EGFR L861Q • EGFR G719X • EGFR S768I
|
Tagrisso (osimertinib)
over1year
The fully automated Idylla™ system offers rapid (turnaround time of approximately 2.5 hours) and reliable testing of clinically actionable mutations in EGFR directly from FFPE tissue sections. In our center, it will complement NGS testing by providing rapid EGFR results within 1-2 days of diagnosis.
EGFR (Epidermal growth factor receptor)
|
EGFR mutation • EGFR L858R • EGFR exon 19 deletion • ATM mutation • EGFR L861Q • EGFR S768I • EGFR G719A • EGFR G719C
almost2years
P1/2, N=97, Recruiting, Millennium Pharmaceuticals, Inc. | Active, not recruiting --> Recruiting
Clinical • Enrollment open
|
EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2)
|
EGFR mutation • EGFR L858R • EGFR T790M • EGFR exon 19 deletion • EGFR exon 20 insertion • EGFR L861Q • HER-2 exon 20 insertion • EGFR G719X • EGFR S768I • EGFR exon 20 mutation • EGFR L861R
|
carboplatin • pemetrexed • Exkivity (mobocertinib)
almost2years
P1/2, N=97, Active, not recruiting, Millennium Pharmaceuticals, Inc. | N=341 --> 97
Clinical • Enrollment change
|
EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2)
|
EGFR mutation • EGFR L858R • EGFR T790M • EGFR exon 19 deletion • EGFR exon 20 insertion • EGFR L861Q • HER-2 exon 20 insertion • EGFR G719X • EGFR S768I • EGFR exon 20 mutation • EGFR L861R
|
carboplatin • pemetrexed • Exkivity (mobocertinib)
almost2years
P1/2, N=341, Active, not recruiting, Millennium Pharmaceuticals, Inc. | Recruiting --> Active, not recruiting
Clinical • Enrollment closed
|
EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2)
|
EGFR mutation • EGFR L858R • EGFR T790M • EGFR exon 19 deletion • EGFR exon 20 insertion • EGFR L861Q • HER-2 exon 20 insertion • EGFR G719X • EGFR S768I • EGFR exon 20 mutation • EGFR L861R
|
carboplatin • pemetrexed • Exkivity (mobocertinib)
almost2years
Clinical • Enrollment open • EGFR exon 20
|
HER-2 (Human epidermal growth factor receptor 2)
|
EGFR L858R • EGFR exon 19 deletion • EGFR exon 20 insertion • EGFR L861Q • EGFR G719X • EGFR S768I • EGFR exon 20 mutation
|
cisplatin • carboplatin • pemetrexed • Exkivity (mobocertinib)
almost2years
P2, N=1, Terminated, University of California, San Francisco | N=27 --> 1 | Trial completion date: Sep 2021 --> Sep 2019 | Recruiting --> Terminated; Low Accrual
Clinical • Enrollment change • Trial completion date • Trial termination
|
EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NF1 (Neurofibromin 1)
|
EGFR mutation • EGFR L858R • EGFR T790M • EGFR exon 19 deletion • ALK rearrangement • NF1 mutation • EGFR L861Q • ROS1 rearrangement • EGFR S768I • EGFR G719A
|
Mekinist (trametinib)
almost3years
P=N/A, N=4, Completed, Memorial Sloan Kettering Cancer Center | Recruiting --> Completed | Trial primary completion date: May 2018 --> Dec 2017
Clinical • Trial completion • Trial primary completion date
|
EGFR (Epidermal growth factor receptor)
|
EGFR mutation • EGFR L858R • EGFR exon 19 deletion • EGFR L861Q • EGFR S768I • EGFR G719A • EGFR exon 19 insertion
|
erlotinib