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- |||| sotorasib (AMG 510) / Amgen
Clinical: CodeBreaK 100: P1 in 59 lung pts. Sotorasib; 960mg is recommended dose;ORR 32% ; DCR 88%. #LCSM #ESMO20 (Twitter) - Sep 20, 2020
- ||||| sotorasib (AMG 510) / Amgen
Clinical: #ESMO20 Overall, sotorasib showing clear efficacy (RR 32.2%, DOR 10.9m, PFS 6.3m) and excellent safety profile. Would have a clear role today in salvage setting. Good safety profile makes it an appealing candidate for combinations in the 1L setting. #LCSM @OncoAlert (Twitter) - Sep 20, 2020
- |||||| sotorasib (AMG 510) / Amgen
Clinical, PD(L)-1 Biomarker, IO Biomarker: #ESMO20 Efficacy of sotorasib seen across KRAS G12C MAFs and TMB levels (by ctDNA). PDL1 predictive. Responses seen across co-mutations as well, though need larger numbers and need to correlate with duration/resistance, not just response. #LCSM @OncoAlert (Twitter) - Sep 20, 2020
- |||| sotorasib (AMG 510) / Amgen
#ESMO20 Median PFS with sotorasib in KRAS G12C NSCLC was 6.3m. Respectable in this setting but duration of response more impressive at 10.9m and long duration noted across doses. Median duration of SD was 4m which is not that long - casts the 90% DCR in a different light. #LCSM (Twitter) - Sep 20, 2020
- ||||| sotorasib (AMG 510) / Amgen, docetaxel / Generic mfg.
Clinical: #ESMO20 Waterfall plot showing efficacy of sotorasib. Responses seen across dose levels, reassuring if dose reduction needed. ORR of 32.5% in a heavily pretreated population is impressive (docetaxel/ramucirumab ~ 23% for reference) with high SD rates (but how durable?). #LCSM (Twitter) - Sep 20, 2020
- ||||| sotorasib (AMG 510) / Amgen
Clinical: #ESMO20 Efficacy of sotorasib in KRAS G12C NSCLC. ORR 32.2% with some reduction noted in 71.2% of patients at 6 weeks and an overall DCR of 88.1% (91.2% at 960mg). ORR lower than earlier reports, as expected, but still high in this setting. High SD rate but how durable? #LCSM (Twitter) - Sep 20, 2020
- ||||| sotorasib (AMG 510) / Amgen
Clinical: #ESMO20 KRAS G12C doesn't occur on normal tissue so the toxicity profile of sotorasib is very good. No DLTs. No fatal AEs. Only 1 patient stopped due to treatment related AE. #LCSM @OncoAlert (Twitter) - Sep 20, 2020
- ||||| sotorasib (AMG 510) / Amgen
Clinical, P1 data, Monotherapy: #ESMO20 CodeBreak100 is a phase I escalation/expansion trial of sotorasib monotherapy in KRAS G12C tumors. Primary endpoint was safety. Escalation established preferred dose of 960mg qday. #LCSM @OncoAlert (Twitter) - Sep 20, 2020
- |||| sotorasib (AMG 510) / Amgen
#ESMO20 KRAS G12C occurs in 13% of NSCLC, 3-5% CRC, and other tumors as well. Up until recently, considered "undruggable". Sotorasib is a highly selective KRAS G12C inhibitor that traps KRAS in its inactive GDP bound state. #LCSM @OncoAlert (Twitter) - Sep 20, 2020
- |||| sotorasib (AMG 510) / Amgen
#ESMO20 Much anticipated results from CodeBreaK100: AMG 510 (sotorasib) in #KRAS G12C #NSCLC by @DavidHongMD building on exciting data seen over the past two years for this huge unmet need. #LCSM @OncoAlert @myESMO (Twitter) - Sep 20, 2020
- ||| sotorasib (AMG 510) / Amgen
Landmark paper of AMG 510 (sotorasib), the #KRAS G12C inhibitor, in solid tumors is now available @NEJM - congratulations to @DavidHongMD and the entire team! #ESMO20 @OncoAlert https://t.co/RXdsxugJnZ (Twitter) - Sep 20, 2020
- |||| sotorasib (AMG 510) / Amgen
$AMGN's sotorasib (Kras inhibitor) update via #ESMO20 & NEJM $MRTX (Twitter) - Sep 20, 2020
- ||| defactinib (VS-6063) / Verastem, VS-6766 / Verastem, sotorasib (AMG 510) / Amgen
Vs-6766 (RO5126766) G12V G12D + synergistic data with G12C AMG510 + FAK Defactinib https://t.co/VDN8PpYoQW (Twitter) - Sep 18, 2020
- |||||| sotorasib (AMG 510) / Amgen
Clinical: #ESMO20 Likewise important to keep in mind: 👇🏾Other tumor types with #KRASG12C 🎯 #AMG510 💊 <sotoRAS🧬-ib> - has a name now❗️ We now have a master protocol examining multiple ⛔️upstream/downstream➕#immunotherapy. @OncoAlert Good to see 🆕other💊. https://t.co/CYPpBYxJwA (Twitter) - Sep 17, 2020
- || Lumakras (sotorasib) / Amgen
Trial completion date, Combination therapy, Monotherapy, Metastases: A Phase 1/2, Study Evaluating the Safety, Tolerability, PK, and Efficacy of Sotorasib (AMG 510) in Subjects With Solid Tumors With a Specific KRAS Mutation (CodeBreaK 100) (clinicaltrials.gov) - Sep 16, 2020
P1/2, N=533, Recruiting, Sponsor: Amgen
Trial completion date: Dec 2023 --> Mar 2024
- ||| Lumakras (sotorasib) / Amgen
Trial completion date, Metastases: Study to Compare AMG 510 "Proposed INN Sotorasib" With Docetaxel in Non Small Cell Lung Cancer (NSCLC) (CodeBreak 200). (clinicaltrials.gov) - Sep 16, 2020
P3, N=650, Recruiting, Sponsor: Amgen
Trial completion date: Dec 2023 --> Mar 2024 Trial completion date: Dec 2027 --> Nov 2028
- |||| amivantamab (JNJ-61186372) / Genmab, J&J, sotorasib (AMG 510) / Amgen
#ESMO20 #LungCancer track 🚨Do not miss the Proffered Paper - NSCLC metastatic 1 (20 Sep - 14.25 CET) chaired by @LeciaSequist and N Leighl. New data about AMG510 for #KRAS disease & Amivantamab for EGFR+ disease Stay tuned! @EGFRResisters @kRasKickers @METCrusaders (Twitter) - Sep 16, 2020
- || sotorasib (AMG 510) / Amgen
A3 I am eager to see the AMG 510 (sotorasib) updates. #fiercetalksesmo Previous data was promising but the durability of those responses would be important (Twitter) - Sep 15, 2020
- |||| sotorasib (AMG 510) / Amgen
Biomarker, Clinical: 1257O - Durability of clinical benefit and biomarkers in patients (pts) with advanced non-small cell lung cancer (NSCLC) treated with AMG 510 (sotorasib) (Twitter) - Sep 15, 2020
- sotorasib (AMG 510) / Amgen
[VIRTUAL] The integrated stress response exposes a therapeutic vulnerability in KRAS driven lung cancer (Channel 3) - Sep 7, 2020 - Abstract #AACRNCIEORTC2020AACR_NCI_EORTC_426;
The significance of our data is highlighted by the ability of ISR inhibitors to impair lung tumor growth with different KRAS mutations. Our findings provide a novel rationale for implementing ISR-based regimens in lung adenocarcinoma treatment.
- SNS-229 / Sunesis, Biogen, SNS-510 / Sunesis
[VIRTUAL] PDK1 inhibitor SNS-510 shows synergy with targeted cancer therapies in solid tumor and hematologic cancer models () - Sep 7, 2020 - Abstract #AACRNCIEORTC2020AACR_NCI_EORTC_292;
The observed synergies support a potential role of PDK1 inhibition to reverse resistance and/or improve activity of CDK4/6i in breast cancer, BCL2i in lymphoma and K-Rasi in G12C mutated cancers. Each combination will be further characterized in xenografts/PDXs studies.
- SNS-229 / Sunesis, Biogen, SNS-510 / Sunesis
[VIRTUAL] PDK1 inhibitor SNS-510 shows synergy with targeted cancer therapies in solid tumor and hematologic cancer models () - Sep 7, 2020 - Abstract #AACRNCIEORTC2020AACR_NCI_EORTC_291;
The observed synergies support a potential role of PDK1 inhibition to reverse resistance and/or improve activity of CDK4/6i in breast cancer, BCL2i in lymphoma and K-Rasi in G12C mutated cancers. Each combination will be further characterized in xenografts/PDXs studies.
- repotrectinib (TPX-0005) / Turning Point Therapeutics, ZAI Lab
[VIRTUAL] Repotrectinib Increases KRAS-G12C Inhibitor Effectiveness Via Simultaneous Inhibition of SRC, FAK, and JAK2 () - Sep 7, 2020 - Abstract #AACRNCIEORTC2020AACR_NCI_EORTC_254;
In preclinical studies, simultaneous inhibition of SRC/FAK/JAK2 by repotrectinib has a range of effects that synergize with KRAS-G12C inhibitor pharmacology and suppress mechanisms of resistance. Further investigation for the potential to increase the duration of response for KRAS-G12C inhibitor therapies is warranted.
- repotrectinib (TPX-0005) / Turning Point Therapeutics, ZAI Lab
[VIRTUAL] Repotrectinib Increases KRAS-G12C Inhibitor Effectiveness Via Simultaneous Inhibition of SRC, FAK, and JAK2 () - Sep 7, 2020 - Abstract #AACRNCIEORTC2020AACR_NCI_EORTC_253;
In preclinical studies, simultaneous inhibition of SRC/FAK/JAK2 by repotrectinib has a range of effects that synergize with KRAS-G12C inhibitor pharmacology and suppress mechanisms of resistance. Further investigation for the potential to increase the duration of response for KRAS-G12C inhibitor therapies is warranted.
- |||| Clinical: $BNTX Ph1 TNBC-MERIT (mono & combo BNT122) at #ESMO20 $MRK Ph3 Keynote-54 vs placebo Final Data #ESMO20 $BMY Ph1 LSD1 Inh in NHL & BET inh at #ESMO20 $AMGN Ph1 CODEBREAK (amg 510+Keytruda) dose expansion, DoR in NSCLC at #ESMO20 $NVS Ph3 ASCEMBL 3L in CML $AXSM Ph2 AXS05 in MDD (Twitter) - Sep 6, 2020
- || Review, Journal: KRAS: From undruggable to a druggable Cancer Target. (Pubmed Central) - Aug 30, 2020
Additionally, various other approaches including, SHP2, SOS1 and eIF4 inhibition, have been utilized to abrogate tumor growth in K-RAS mutant cells, resulting in a renewed interest in this pathway. In this review article, we provide an overview on the role of K-RAS in tumorigenesis, past approaches to inhibiting Kras, and current and future prospects for targeting Kras.
- ||| sotorasib (AMG 510) / Amgen
I had one IDH mut NSCLC adeno smoker progress after 9 m chemo-IO, found on FMI.Nothing in https://t.co/2OPG4eBYHJ, didn’t know what to do.Only other mut was KRAS G12C. Gave him TXT-Ramucirumab thinking that IDHmut GBM responds to antiangiogen but he PD.Trying to give AMG510 now (Twitter) - Aug 30, 2020
- ||| MRTX849 / Mirati, sotorasib (AMG 510) / Amgen
Clinical data: Certainly a very interesting approach in the increasingly competitive field. Looking forward to the clinical data! Will be interesting how it will compare against the G12C specific drugs #AMG510 and #MRTX849. (Twitter) - Aug 19, 2020
- || sotorasib (AMG 510) / Amgen
Review, Journal, Liquid Biopsy: KRAS mutations testing in non-small cell lung cancer: the role of Liquid biopsy in the basal setting. (Pubmed Central) - Aug 18, 2020
In advanced stage non-small cell lung cancer (NSCLC) patients, Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) testing may soon acquire a predictive significance to select patients for AMG510 treatment...In conclusion, our data update and confirm that SiRe NGS panel represents a robust analytical tool to assess KRAS mutational status on circulating tumor DNA. Further investigation is required to design more cost-effective diagnostic algorithms to harmonize clinical relevant biomarker testing on tissue and blood in advanced stage NSCLC clinical practice.
- || sotorasib (AMG 510) / Amgen
I don't follow that conference. is AMG-510 on it (w/ & w/o ICI?) (Twitter) - Aug 10, 2020
- || sotorasib (AMG 510) / Amgen
Marwan Fakih, MD on CodeBreak 100: Activity of AMG 510 #ASCO2020 https://t.co/sUcWm1MlI5 (Twitter) - Aug 5, 2020
- | MRTX849 / Mirati, sotorasib (AMG 510) / Amgen
Journal: Sticking it to KRAS: Covalent Inhibitors Enter the Clinic. (Pubmed Central) - Aug 4, 2020
Recent papers describe development of these compounds, their selectivity and properties, early clinical data, and potential combination therapies. These papers herald a new era in Ras research, with improved drugs and strategies certain to follow.
- || AbGn-107 / AbGenomics, sotorasib (AMG 510) / Amgen
AMG 510, AbGn-107 Prove to Be Effective, Tolerable in GI Cancers https://t.co/c93XcESshN via @onclive (Twitter) - Aug 2, 2020
- ||||| MRTX849 / Mirati, sotorasib (AMG 510) / Amgen
We opened the #AMG510, which now has a name: #KRASG12C⛔️ AMG-510 💊 <sotoRAS🧬-ib> Multiple arms being examined e.g. ➕MEK⛔️ downstream. https://t.co/0PKjcyhpIN #MRTX849 is the other one active in trials across many sites. Besides #lcsm #CRCSM imp. to recognize others👆🏾. (Twitter) - Jul 30, 2020
- ||| sotorasib (AMG 510) / Amgen
$AMGN sotorasib (remember Kras?!) ph1 NSCLC data at #ESMO20 $MRTX (Twitter) - Jul 29, 2020
- ||||| sotorasib (AMG 510) / Amgen
#ICYMI: In a previous episode of #OncLiveOnAir, @alexdrilon, of @sloan_kettering, shares insight on some of the historical challenges of targeting KRAS and provided perspective on available and anticipated data with AMG 510 in NSCLC. #lcsm Listen now: https://t.co/BbpSStL3FB! (Twitter) - Jul 25, 2020
- sotorasib (AMG 510) / Amgen, docetaxel / Generic mfg.
[VIRTUAL] CodeBreak 200: A phase III multicenter study of sotorasib (AMG 510), a KRAS(G12C) inhibitor, versus docetaxel in patients with previously treated advanced non-small cell lung cancer (NSCLC) harboring KRAS p.G12C mutation (On-Demand) - Jul 24, 2020 - Abstract #ESMO2020ESMO_2196;
P1/2, P3
Funding: Amgen Inc. Clinical trial identification: NCT04303780.
- sotorasib (AMG 510) / Amgen
[VIRTUAL] Durability of clinical benefit and biomarkers in patients (pts) with advanced non-small cell lung cancer (NSCLC) treated with AMG 510 (sotorasib) (Channel 1) - Jul 21, 2020 - Abstract #ESMO2020ESMO_1185;
P1/2
Funding: Amgen Inc. Clinical trial identification: NCT03600883.
- | sotorasib (AMG 510) / Amgen
Journal: KRAS(G12C)-AMG 510 interaction dynamics revealed by all-atom molecular dynamics simulations. (Pubmed Central) - Jul 21, 2020
N-terminally modified KRAS displays similar interaction dynamics with AMG 510 as when Met1 is present, but this PTM appears to stabilize β2-β3-loop. These results provide novel conformational insights on the molecular level to KRAS(G12C)-AMG 510 interactions and dynamics, providing new perspectives to RAS related drug discovery.
- |||| AbGn-107 / AbGenomics, sotorasib (AMG 510) / Amgen
AMG 510, AbGn-107 Prove to Be Effective, Tolerable in GI Cancers @SeattleCCA #hpbcsm https://t.co/thc8AeosbK (Twitter) - Jul 10, 2020
- ||||| sotorasib (AMG 510) / Amgen
In our latest episode of #OncLiveOnAir, @alexdrilon, of @sloan_kettering, discusses some of the historical challenges of targeting KRAS and provides perspective on anticipated data with AMG 510 in non–small cell lung cancer https://t.co/d59c612hXR (Twitter) - Jul 3, 2020
- || sotorasib (AMG 510) / Amgen
Clinical, Journal: Clinical characteristics and prognostic value of the KRAS G12C mutation in Chinese non-small cell lung cancer patients. (Pubmed Central) - Jul 3, 2020
At the 2019th World Conference of Lung Cancer, the KRAS G12C-specific inhibitor AMG510 showed promising results in the phase I clinical trial...Of these, nearly 30% harbored the KRAS G12C mutation subtype, which was most common in male smokers. The KRAS G12C mutation is a biomarker of poor prognosis in Chinese NSCLC patients, which could potentially be improved by G12C-specific inhibitors in the future.(296 words).
- ||||| sotorasib (AMG 510) / Amgen
Clinical: #WorldGI2020 @myESMO @OncoAlert KRAS-G12C⛔️ AMG-510 💊 <sotoRAS🧬-ib> CODEBreaK100 #ClinicalTrials Exciting to see some drugs for our KRAS-mutant #cancer patients. ~12% of #LCSM ~2% of #CRCSM Also 6 patients here had #PANCSMz (Twitter) - Jul 3, 2020
- ||||| sotorasib (AMG 510) / Amgen
Clinical: Activity of AMG510 in KRAS G12C mutated mCRC appears dose-dependent. Not as impressive as in lung cancer, but toxicity is mild and it could be an option for the 3% of pts with this KRAS mutation. @OncoAlert #WorldGI2020 (Twitter) - Jul 3, 2020
- ||||| sotorasib (AMG 510) / Amgen
JUST RELEASED: In our latest episode of #OncLiveOnAir, @alexdrilon, of @sloan_kettering, discusses some of the historical challenges of targeting KRAS and provides perspective on available and anticipated data with AMG 510 in NSCLC. #lcsm Listen now: https://t.co/At1h2IXoRw (Twitter) - Jul 2, 2020
- ||||| sotorasib (AMG 510) / Amgen
Clinical: Didn’t know that the KRAS-G12C⛔️ AMG-510 💊 Now has a name: <sotoRAS🧬-ib> CODEBreaK100 #ClinicalTrials Exciting to see some drugs for our KRAS-mutant #cancer patients. ~12% of #LCSM ~2% of #CRCSM I’ve seen 6️⃣this year; 1 yesterday. Not that rare. #WorldGI2020 #oncoalert (Twitter) - Jul 2, 2020
- | sotorasib (AMG 510) / Amgen
Journal: Discovery of a covalent inhibitor of KRASG12C (AMG 510) for the treatment of solid tumors. (Pubmed Central) - Jul 2, 2020
P1/2
Structure-based design efforts leading to the identification of a novel quinazolinone scaffold are described, along with optimization efforts that overcame a configurational stability issue arising from restricted rotation about an axially chiral biaryl bond. Biopharmaceutical optimization of the resulting leads culminated in the identification of AMG 510, a highly potent, selective, and well-tolerated KRASG12C inhibitor currently in Phase I clinical trials (NCT03600883).
- |||| sotorasib (AMG 510) / Amgen
As for single agent AMG510, good activity in #lcsm , reasonable activity in advanced #crcsm . Most probably needs to be developed in synergistic combinations (MEK / ICI). (Twitter) - Jun 22, 2020