EGFR T790M

#ASCO23 #LCSM 📢 Safety and efficacy of YK-029A, a new EGFR TKI, in advanced NSCLC with ex20ins, T790M or rare mutations 👩‍🔬🧪. ➡️ Phase 1 trial, 108 patients 🧑‍🤝‍🧑. ➡️ Most common TRAEs: diarrhea (46.3%), anemia (38.0%), and rash (32.4%) 🌡️. ➡️ For the EGFR ex20ins cohort, objective… https://t.co/gm2d0dNZY0 (@ADesaiMD)

Congrats to @MGHBreastOnc on this paper showing how a panel of resistance alterations complement ESR1 to inform outcomes to CDK4/6i in MBC! Like T790M in NSCLC, ESR1 is going to just be the tip of the resistance iceberg... https://t.co/HvVp0w8Bjz (@geoff_oxnard)

Osimertinib in patients experienced progression after 1st or 2nd gen EGFR-TKIs without T790M (WJOG12819L (KISEKI) @JSMO_official by Dr. Daisuke Hayakawa. ORR of 29.1% (95% CI,17.6-42.9) was demonstrated and met the pre-planned significance boundary. #JSMO2023 #LCSM (@HHorinouchi)

#FeatureFriday Today on #FeatureFriday, we are featuring a tweet from Dr. Antonio Passaro [@APassaroMD] on how #Osimertinib, an #EGFR-tyrosine kinase inhibitor, potently and selectively inhibits EGFR-TKI-sensitizing and EGFR T790M resistance mutations in advanced NSCLC. (@4baseCare)

🩸🧬 Analysis of acquired resistance to osimertinib in EGFR-mutated advanced NSCLC pts from the AURA3 trial: 50% undetectable plasma EGFR T790M, 19% have >1 resistance-mechanism: MET amplification (14/78, 18%) and EGFR C797X mutation (14/78, 18%). #LCSM https://t.co/r7V1qLfr4C (@Tony_Calles)

Phase II EORTC Lung Cancer Group 1613 APPLE trial @Annals_Oncology. Pts with #EGFR mutant NSCLC randomized to osimertinib until PD, gefitinib until PD, or gefitinib until either T790M+ by ctDNA or PD. ctDNA led to earlier switch to osimertinib in 17%. https://t.co/TwKmrtswkC (@StephenVLiu)

This is analogous to the initial approval of osimertinib only for EGFR-mutant lung cancers that acquired the T790M resistance mutation, but everyone could see that it was better than other TKIs in the first line, without T790M, as the FLAURA trial eventually showed. (@UnfrznCavemanMD)

A real-world study of second or later-line osimertinib in patients with EGFR T790M-positive NSCLC: the final ASTRIS data | Future Oncology https://t.co/nSW3k53kse (@MARIANOPROVENCI)

Report of oleclumab (anti-CD73) plus osimertinib in #EGFR NSCLC @JTOonline. CD73 often overexpressed in EGFR mutant NSCLC. Explored post 1G/2G TKI, T790M negative, osi naive. At dose level 2, RR 12% with mPFS 7.4m, mOS 25m. https://t.co/we5zEtPi4r (@StephenVLiu)

Excited to share this as co-first author! 1.#EGFR detection: 💧PE-#cfDNA🧬 sensitivity > plasma (97 vs 74%) 2. PE-cfDNA🧬 detects more #T790M than cyto🔬 (high QI rate) Thanks to #KirstyLee @TonyMok9 and all colleagues! https://t.co/sXp6wRFOIw @JAMAOnc @CUHKMedicine #LCSM (@mollylisc)

Testing Pleural and Pericardial Effusion for EGFR Variants in NSCLC @JAMAOnc 💥EGFR sensitizing variants PE-cfDNA sensitivity and specificity➡️ 97% Plasma➡️74% 💥T790M variant PE-cfDNA sensitivity ➡️87% ☑️Effusions can be analyzed with high accuracy https://t.co/bNC9clmgSb (@dr_yakupergun)

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)

Phase Ib study of telisotuzumab vedotin (teliso-V, #MET ADC) + erlotinib in cMET+ #EGFR mutant NSCLC @JCO_ASCO. RR 32% in EGFRmt and RR 53% in cMET high (H-score ≥225) with mPFS 6.8m in T790M+. Neuropathy seen in 57%. https://t.co/GFRalewa4v (@StephenVLiu)

🚨🚨 Check out our latest collaboration: #UNICORN: UNcommon EGFR mutations: International Case series on efficacy of #osimertinib in 1st liNe J Bair et al. ▶️N=60, G719X L861Q & T790M ▶️ORR 61%, mOS 24.5m. compound EGFR+ did better @EGFRResisters #lcsm https://t.co/7CqrcJpiXr (@Latinamd)

In this multi-center, retrospective study @JTOonline for uncommon EGFR mutation (n=60), osimertinib demonstrated an ORR of 61% (44% for denovo T790M, 47% for G719X ORR & 80% for L861Q) Md PFS 9.5 mo Md DOR 17.4 mo & Md OS of 24.5 mo #LCSM @OncoAlert https://t.co/XxvURqgISg (@dipeshuprety4)

Osimertinib in NSCLC w uncommon EGFR mutns @JTOonline: - 60pt retrosp study, overall ORR 66% - G719X ORR 47% mPFS 8.8m mDOR 9.1m - L861Q ORR 80% mPFS 16m mDOR 16m - de novo T790M ORR 44% mPFS 12.7m mDOR 46.2m ?⬇️ORR T790M than expected, important study https://t.co/B3kpq7AKbR (@DrJNaidoo)

Ph Ib TATTON (Part B) trial: Osi+Selumetinib in EGFR-mt NSCLC post EGFR-TKI: - 47pts (prior 1/2nd gen TKI=12; prior T790M-TKI=35) - ORR 67% & 22.9%; mPFS 15.0mo; 2.8mo respectively Osi+MEKi has modest 2L activity, but is the area of greatest need #LCSM https://t.co/HNJXQIscD4 (@DrJNaidoo)

Efficacy and Safety of Befotertinib (D-0316) in Patients With EGFR T790M-Mutated NSCLC That Had Progressed After Prior EGFR Tyrosine Kinase Inhibitor Therapy: A Phase 2, Multicenter, Single-Arm, Open-Label Study - Journal of Thoracic Oncology https://t.co/A1lp5GJDBU (@AdnanNagrial)

Dr. @JordiRemon presents results from the @EORTC phase II randomized APPLE trial at #ESMO22. Randomized pts with #EGFR NSCLC to 1L osimertinib vs gefitinib then osimertinib at RECIST PD (if T790M+) vs gefitinib then osimertinib when T790M+ in liquid biopsy (cobas assay). #LCSM (@StephenVLiu)

#ESMO22 #LCSM @JordiRemon presented the APPLE trial in EGFR+ NSCLC: osi treatment based on plasma T790M @EORTC Study design, here! (@APassaroMD)

Phase IIb study of rezivertinib (BPI-7711, 3G #EGFR TKI) in T790M NSCLC @JTOonline (n=226, 2019-20). With 2y f/u, RR 64.6%, mDOR 12.5m, mPFS 12.2m, mOS 23.9m, CNS RR 69%. No interstitial lung disease. Phase III REZOR trial vs gefitinib already completed. https://t.co/yvE6JdaGBx (@StephenVLiu)

Thanks for your reply Dr. Umut. Lqd biopsy says T790M negative. PB/ TP53 positive. May be from the biopsy SCLC trans could be checked and if no, then NGS for resistance mechanism? (@siddhar99256978)

Another 3rd generation #EGFR TKI with results reported @JTOonline. Befotertinib (D-0316) was studied in pts with EGFR T790M NSCLC and at 75-100mg, IRC RR 68%, DCR 95%, intracranial RR 57%, mPFS 12.5m. Only 5% diarrhea and no G3+ diarrhea. #LCSM https://t.co/lICva86eNR (@StephenVLiu)

Yep! I can second this. Familial cases of lung cancer have been associated with germline EGFR T790M. We also reported a case associated with myeloid sarcoma: https://t.co/EnYi0L7EYw #TumorBoardTuesday (@LaurenBzak)

Results from single arm phase II study of the 3rd generation #EGFR TKI limertinib (ASK120067) in EGFR T790M NSCLC now @JTOonline. Study launched in 2019 and included 301 pts. RR 69%, mPFS 11m, mOS not reached, intracranial RR 56%. G3+ diarrhea in 13%. https://t.co/fUB1aiJ8HG (@StephenVLiu)

Retrospective report @JTOonline: in #EGFR mutant NSCLC, co-mutations in TP53 are associated with more rapid development of resistance, even among pts with initial response to therapy and across various mechanisms of resistance (SCLC, T790M). #LCSM @IASLC https://t.co/XpjLQ9oyHB (@StephenVLiu)

#TTLC22 P10 by Dr. @cbmeador described #EGFR NSCLC with squamous histology (at diagnosis or after transformation). Interesting that for some, squamous transformation was concurrent with genomic evolution (MET, T790M). Likely underdiagnosed - biopsy at progression is important. (@StephenVLiu)

Phase I results of the 3rd generation #EGFR TKI rezivertinib (BPI-7711) in EGFR T790M NSCLC @JTOonline. No DLTs and no cases of pneumonitis. In 172pts, RR 59% with mPFS 9.7m. Intracranial RR 50%. RP2D 180mg daily. #LCSM https://t.co/q1B1KxuPDv (@StephenVLiu)

Phase I/II study of lazertinib (3G EGFR TKI) in #EGFR mutant with T790M @JTOonline shows RR 55%, mPFS 11m, intracranial RR 86%, good safety profile. I have equipoise with a study using lazertinib instead of osimertinib. #LCSM https://t.co/PXxltnC08M (@StephenVLiu)

Just out in @LungCaJournal : Sequential afatinib ➡️ osimertinib in patients with EGFR mutation-positive NSCLC and acquired T790M: A global non-interventional study (UpSwinG) by @DrSanjayPopat & colleagues @EGFRResisters @EgfrUk 👇🏼 https://t.co/ZgpoHJRZNL (@LungCaJournal)

ETOP-BOOSTER trial osimertinib+Bev v osi in 2L EGFR T790M+ NSCLC: No PFS/OS benefit - mPFS 15.4 v 12.3m, HR 0.96 - mOS 24 v 24.3m, HR 1.03 More tox - G3+ TRAEs 47 v 18% While 1L std of care is osi & T790M is no longer used, imp data we can learn from https://t.co/VuB0xnIoz4 (@DrJNaidoo)

Results from the ETOP BOOSTER trial now @Annals_Oncology. Randomized phase II study of 2nd line osimertinib +/- bevacizumab in #EGFR T790M+ NSCLC. There was no difference in RR, PFS or OS and more toxicity with the combination. #LCSM @ETOP_eu @OncoAlert https://t.co/BrVk0YCVBf (@StephenVLiu)

This ETOP study enrolled 155 pts with #EGFR NSCLC and acquired T790M after prior TKI therapy. Randomized to osimertinib 80mg/d alone or with bevacizumab 15mg/kg q3w. With 34m median f/u, no difference in PFS (primary endpoint): 15.4m osi/bev vs 12.3m osi alone (HR 0.96). (@StephenVLiu)

Amazing discovery by Susumu Kobayashi (ala T790M fame), Koichi Goto and Co💪🙏 👀we can add the 10th actionable marker to our NSCLC magic cube- w available tx - lorla right away! Happy Thxgiving #lcsm! The CLIP1–LTK fusion is an oncogenic driver in NSCLC https://t.co/3Vu82EBSYZ (@DrSteveMartin)

Efficacy of Aumolertinib in EGFR T790M+ NSCLC: Updated Results from the APOLLO Registrational Trial Looking forward to having a lower cost alternative to osimertinib around the world @EQRxINC (in the pic phase 3 results vs gefitinib in first line) https://t.co/T1aiqJ3AB6 (@GlopesMd)

Updated data from the APOLLO study of the 3rd gen #EGFR TKI aumolertinib (HS-10296, 110mg daily) in EGFR T790M NSCLC. RR 69%, DCR 93%, mDOR 15m, mPFS 12.4m, CNS RR 61%. Seems comparable to osimertinib. Aumolertinib approved in China. Bound for US? #LCSM https://t.co/fIPHAPhuNf (@StephenVLiu)

Integrative Profiling of T790M-Negative EGFR-Mutated NSCLC Reveals Pervasive Lineage Transition and Therapeutic Opportunities https://t.co/5831RtF1BX (@AndresFCardonaZ)

Results from the phase II OCEAN study now @JTOonline: CNS efficacy of osimertinib 80mg in 39 pts with #EGFR T790M NSCLC and untreated brain metastases. Brain metastasis RR 67%, RECIST RR 40% and brain metastasis related PFS of 25 months. #LCSM @OncoAlert https://t.co/jyJrEg11cJ (@StephenVLiu)

Agree, lung is the obvious exception, with T790M on cfDNA. If new BRAF-dimerization agents proceed to clinic, melanoma would be another exception. But for now, tumour rebiopsy outside clinical trials would seem to be... pointless... (@DrCraigGedye)

How to overcome resistance to #egfr whether dependent or independent ⁦⁦@SukiPaddaMD⁩ ⁦@gotoPER⁩ #ilc2021 #lungcancer #lcsm ⁦@CedarsSinai⁩ with cochairs ⁦@drgandara⁩ ⁦@DrRoyHerbstYale⁩ ⁦@HwakeleeMD⁩ loss of T790M in 42-68% of nsclc (@donnashort)

Report in #JTOCRR of afatinib + xentuzumab (IGF-ligand neutralizing monoclonal) in #EGFR mutant NSCLC post TKI (non T790M). Seemed safe but no responses noted. Targeting IGFR has been disappointing (recall Clovis CO-1686, rociletinib). @JTOonline @IASLC https://t.co/l23gUG7XMa (@StephenVLiu)

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)