Lumakras (sotorasib) / Amgen 
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  • ||||||||||  Lumakras (sotorasib) / Amgen
    Enrollment change, Trial completion date, Trial withdrawal, Trial primary completion date, Metastases:  Study of Sotorasib Combined With Chemotherapy for Second Line Treatment of Pancreas Cancer (clinicaltrials.gov) -  Feb 8, 2023   
    P1/2,  N=0, Withdrawn, 
    N=59 --> 0 | Trial completion date: Jan 2025 --> Jan 2023 | Recruiting --> Withdrawn | Trial primary completion date: Jan 2024 --> Jan 2023
  • ||||||||||  Lumakras (sotorasib) / Amgen
    Journal:  A Rare Event of Liver Dysfunction on Sotorasib and Management Strategy. (Pubmed Central) -  Feb 3, 2023   
    This is significant and requires withholding treatment as it can be life-threatening in some cases. The following case study outlines a patient who developed abnormal liver enzyme elevation while on the phase I clinical trial of sotorasib, and the management of this event.
  • ||||||||||  Krazati (adagrasib) / Mirati, Lumakras (sotorasib) / Amgen
    Preclinical, Journal:  143D, a novel selective KRAS inhibitor exhibits potent antitumor activity in preclinical models. (Pubmed Central) -  Feb 2, 2023   
    Moreover, 143D combined with EGFR/MEK/ERK signaling inhibitors showed enhanced antitumor activity both in vitro and in vivo. Taken together, our findings indicate that 143D may be a promising drug candidate with favorable pharmaceutical properties for the treatment of cancers harboring the KRAS mutation.
  • ||||||||||  MDM2 inhibition in combination with MEK inhibition in pre-clinical models of lung adenocarcinomas with MDM2 amplification (Wedgewood Ballroom) -  Jan 28, 2023 - Abstract #IASLCTTLC2023IASLC_TTLC_159;    
    In contrast, ERK phosphorylation was not suppressed by concurrent milademetan and KIF5B::RET inhibition using selpercatinib (in ECLC5-GLx), MET inhibition using capmatinib (in LUAD12c), or KRASG12C inhibition using sotorasib (in SW1573)...In vivo, milademetan+trametinib was more effective than milademetan or trametinib alone in ECLC5-GLx (p<0.0001 and p<0.0001, respectively), LX-285 (EGFRex19del/MDM2amp) (p<0.0001 and p<0.0001, respectively), L-13BS1 (model resistant to capmatinib) (METex14/MDM2amp) (p<0.05 and p<0.0001, respectively)...CONCLUSION Combined MDM2/MEK inhibition is effective in patient-derived LUAD models harboring MDM2amp. This combination, potentially applicable to LUADs with a wide variety of oncogenic driver mutations and kinase fusions will be investigated as part of a phase 1/2 clinical trial.
  • ||||||||||  Rozlytrek (entrectinib) / Roche, Lumakras (sotorasib) / Amgen
    Preclinical, Journal:  Evolution of acquired resistance in a ROS1 KRAS G12C NSCLC through the MAPK pathway. (Pubmed Central) -  Jan 24, 2023   
    Clinical benefit was not observed with combined therapy of entrectinib and sotorasib possibly related to an evolving KRAS p.G12C amplification identified on repeated molecular testing. This case supports the need for broad molecular profiling in patients with metastatic NSCLC for potential therapeutic and prognostic information.
  • ||||||||||  Lumakras (sotorasib) / Amgen
    Review, Journal, IO biomarker:  KRAS Mutations in Solid Tumors: Characteristics, Current Therapeutic Strategy, and Potential Treatment Exploration. (Pubmed Central) -  Jan 22, 2023   
    KRAS G12C inhibitors became the most recent breakthrough in targeted therapy, with Sotorasib being approved by the Food and Drug Administration (FDA) based on its significant efficacy in multiple clinical studies...Thus, other non-target, conventional therapies have also been considered as being promising. Here in this review, we went through the characteristics of KRAS mutations in cancer patients, and the prognostic effect that it poses on different therapies and advanced therapeutic strategy, as well as cutting-edge research on the mechanisms of drug resistance, tumor development, and the immune microenvironment.
  • ||||||||||  ASN007 / Asana BioSci, Erasca, UT MD Anderson Cancer Center, ERAS-601 / Erasca
    Enrollment closed, Phase classification, Metastases:  HERKULES-2: A Study of Anti-Cancer Therapies Targeting the MAPK Pathway in Patients With Advanced NSCLC (clinicaltrials.gov) -  Jan 11, 2023   
    P1b,  N=200, Active, not recruiting, 
    Trial completion date: Dec 2025 --> May 2026 | Trial primary completion date: Nov 2025 --> May 2026 Recruiting --> Active, not recruiting | Phase classification: P1b/2 --> P1b
  • ||||||||||  Lumakras (sotorasib) / Amgen
    Journal:  Design, synthesis and biological evaluation of KRAS-PROTACs. (Pubmed Central) -  Jan 10, 2023   
    Based on AMG-510, a series of novel KRAS-PROTACs were designed and synthesized...Besides,the structure-activity relationships (SARs) of KRAS-PROTACs were summarized. These results supported the use of the PROTAC strategy to degrade oncogene KRAS and provided clues for structural optimization of KRAS-PROTACs.
  • ||||||||||  Journal, Machine learning:  Drug Repurposing against KRAS Mutant G12C: A Machine Learning, Molecular Docking, and Molecular Dynamics Study. (Pubmed Central) -  Jan 9, 2023   
    From 67 FDA-covalent drugs, afatinib, dacomitinib, acalabrutinib, neratinib, zanubrutinib, dutasteride, and finasteride were predicted to be active inhibitors...Therefore, afatinib, neratinib, and zanubrutinib could be used as drug candidates against the KRAS protein. This finding unfolds the benefit of artificial intelligence in drug repurposing against KRAS protein.
  • ||||||||||  Lumakras (sotorasib) / Amgen, VIC-1911 / VITRAC Therap
    Enrollment open, Phase classification, Trial completion date, Trial primary completion date, Combination therapy, Monotherapy:  VIC-1911 Monotherapy in Combination With Sotorasib for the Treatment of KRAS G12C-Mutant Non-Small Cell Lung Cancer (clinicaltrials.gov) -  Jan 6, 2023   
    P1a/1b,  N=140, Recruiting, 
    This finding unfolds the benefit of artificial intelligence in drug repurposing against KRAS protein. Not yet recruiting --> Recruiting | Phase classification: P1 --> P1a/1b | Trial completion date: Nov 2025 --> Nov 2026 | Trial primary completion date: May 2025 --> Mar 2026