Lumakras (sotorasib) / Amgen 
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  • ||||||||||  adagrasib (MRTX849) / Mirati, Lumakras (sotorasib) / Amgen
    Review, Journal:  Targeting KRAS -Mutated Advanced Colorectal Cancer: Research and Clinical Developments. (Pubmed Central) -  Jul 16, 2022   
    As a result, combination therapy trials with EGFR inhibitors are currently underway. Here, we will review the available clinical trial data on KRAS inhibitors in KRAS -mutated CRC, possible mechanisms of resistance to monotherapy, the research studying why available agents are proving to be less efficacious in CRC compared to NSCLC, and future directions for these promising new drugs.
  • ||||||||||  adagrasib (MRTX849) / Mirati, Lumakras (sotorasib) / Amgen
    Review, Journal, IO biomarker:  The treatment of advanced non-small cell lung cancer harboring KRAS mutation: a new class of drugs for an old target-a narrative review. (Pubmed Central) -  Jul 15, 2022   
    Together with the development of new targeted drugs, the development of strategies to control resistance mechanisms is one of the major drivers of research that is exploring the use of KRAS inhibitors not only alone, but also in combination with other targeted therapies, chemotherapy and immunotherapy. This review will describe the major therapeutic developments in KRAS mutation-dependent NSCLC and will analyse future perspectives to maximise benefits for this group of patients.
  • ||||||||||  Lumakras (sotorasib) / Amgen
    Journal:  Synthesis of Substituted Pyridines via Formal (3+3) Cycloaddition of Enamines with Unsaturated Aldehydes and Ketones. (Pubmed Central) -  Jul 6, 2022   
    Mechanistic analysis using two-dimensional nuclear magnetic resonance (NMR) spectrometry revealed the transformation proceeds through the reversible formation of a stable reaction off-cycle species that precedes pyridine formation. In situ reaction progress kinetic analysis and control NMR studies were employed to better understand the role of FeCl and pyrrolidine hydrochloride in promoting the reaction.
  • ||||||||||  adagrasib (MRTX849) / Mirati, Lumakras (sotorasib) / Amgen
    Journal:  KRAS-independent feedback activation of wild-type RAS constrains KRAS inhibitor efficacy. (Pubmed Central) -  Jun 29, 2022   
    Even in colorectal cancer, where feedback is thought to be primarily epidermal growth factor receptor (EGFR)-mediated, alternative RTKs drive pathway reactivation and limit efficacy, but convergent upstream or downstream signal blockade can enhance activity. Overall, these data provide important mechanistic insight to guide therapeutic strategies targeting KRAS.
  • ||||||||||  adagrasib (MRTX849) / Mirati, Lumakras (sotorasib) / Amgen
    Understanding the basis for sensitivity and resistance to KRAS-G12C inhibitors (Poster Area) -  Jun 28, 2022 - Abstract #EACR2022EACR_589;    
    This indicates that there are other factors that influence sensitivity to these inhibitors. in vitro are EMT and changes in the expression and/or activation of some tyrosine kinase receptors.
  • ||||||||||  adagrasib (MRTX849) / Mirati, Lumakras (sotorasib) / Amgen
    RAS(ON) inhibitors overcome clinical adaptive resistance to KRAS G12C covalent blockade (Poster Area) -  Jun 28, 2022 - Abstract #EACR2022EACR_515;    
    Therefore, our preclinical findings can help explain the onset of clinical resistance in those patients where acquired alterations are not detected. We propose that G12Ci-ON inhibitors targeting GTP-bound KRAS may be an effective alternative to treat disease relapse due to adaptive mechanisms of signal reactivation.
  • ||||||||||  Lumakras (sotorasib) / Amgen
    Sotorasib Drug-Drug Interactions: Essential Guidance Requested by Physicians Worldwide (Exhibit Hall - Hall B) -  Jun 24, 2022 - Abstract #IASLCWCLC2022IASLC_WCLC_1003;    
    Questions about real-life drug combinations applied to relevant DDI in approximately half of all cases. Guidance is often requested for DOACs and acid-reducing drugs and often requires intervention when coadministered with sotorasib.
  • ||||||||||  Lumakras (sotorasib) / Amgen
    Real-world Data from KRAS-mutant Advanced NSCLC: the ATLAS Multicenter Cohort Study (Exhibit Hall - Hall B) -  Jun 24, 2022 - Abstract #IASLCWCLC2022IASLC_WCLC_1001;    
    The prevalence of KRAS mutations subtypes as well as the survival outcomes of our cohort of KRAS-mutant advanced NSCLC patients were consistent with those reported in the literature. Such data confirmed once again the high heterogeneity of KRAS-mutant NSCLC population and highlight the urgent need of novel personalized treatment strategies.
  • ||||||||||  SAR442720 / Sanofi, Revolution Medicines, Lumakras (sotorasib) / Amgen
    Sotorasib in Combination with RMC-4630, a SHP2 Inhibitor, in KRAS p.G12C-Mutated NSCLC and Other Solid Tumors (Hall C7) -  Jun 24, 2022 - Abstract #IASLCWCLC2022IASLC_WCLC_903;    
    Promising clinical activity was observed in KRAS p.G12C-mutated NSCLC patients, most notably in those KRASG12C inhibitor-naïve. Dose expansion is underway to further define efficacy and safety in both KRASG12C inhibitor-naïve and KRASG12C inhibitor-exposed NSCLC patients.
  • ||||||||||  Lumakras (sotorasib) / Amgen
    Mechanims of Immune Evasion in Patients With KRAS-Mutant Lung Adenocarcinoma: A Role of MAPK Pathway Activation (Hall C7) -  Jun 24, 2022 - Abstract #IASLCWCLC2022IASLC_WCLC_871;    
    The coordinated infiltration of T-helper and T-regulatory cells, M2 macrophage border and exclusion of cytotoxic T-cells in MAPK-high tumors might contribute to its underlying immune-suppressed state. Our data open the possibility of novel combination therapies, including RAS inhibitors and different immune checkpoint blockers, outside the KRAS-mutant group.
  • ||||||||||  Lumakras (sotorasib) / Amgen
    Aurora A Kinase Inhibition with VIC-1911Potentiates KRASG12C Inhibitor and Overcomes Resistance to Sotorasib in Lung Cancer (Hall C8) -  Jun 24, 2022 - Abstract #IASLCWCLC2022IASLC_WCLC_632;    
    Our findings link AURKA activation to both intrinsic and acquired resistance to sotorasib in KRASG12C-mutated lung cancer and show antitumor activity for AURKA inhibition in these settings. The combination of AURKA inhibition with sotorasib may be a promising therapeutic approach in lung cancer with intrinsic resistance to direct KRASG12C inhibitors, while the combination of AURKA and WEE1 inhibition merits exploration in acquired resistance to these agents.
  • ||||||||||  Lumakras (sotorasib) / Amgen, TNO155 / Novartis
    Targeting SHP2 Reverts Oncogenic Mediated Resistance to KRAS-G12C Inhibition (Exhibit Hall - Hall B) -  Jun 24, 2022 - Abstract #IASLCWCLC2022IASLC_WCLC_607;    
    Our findings introduce HER2 gain as a clinically relevant off-target resistance mechanism to KRAS-G12C inhibition that can be rescued by co-targeting SHP2. This finding adds a rationale for combined targeting of KRAS-G12C and SHP2 in clinical settings.
  • ||||||||||  MRTX1133 / Mirati, Lumakras (sotorasib) / Amgen
    Journal:  Profiling oncogenic KRAS mutant drugs with a cell-based Lumit p-ERK immunoassay. (Pubmed Central) -  Jun 9, 2022   
    However, recent FDA approval of the KRAS G12C selective inhibitor sotorasib (AMG-510), has breathed new life into the drive to develop mutant KRAS inhibitors...An inhibition profile was obtained indicating various potencies and selectivity of the inhibitors, including MRTX-1133, which was shown to be highly potent against KRAS G12D signaling...Our results demonstrate that this bioluminescent technology can streamline the analysis of signaling pathways of interest, such as RAS-dependent pathways, and be used to identify much needed inhibitors. The results further imply that similar assay designs could be applied to other signaling pathway nodes.
  • ||||||||||  DT-061 / University of Maryland, Lumakras (sotorasib) / Amgen
    Journal:  Potential of phenothiazines to synergistically block calmodulin and reactivate PP2A in cancer cells. (Pubmed Central) -  Jun 4, 2022   
    Benchmarking against the KRAS-G12C specific inhibitor AMG-510 in MIA PaCa-2 cells revealed a higher potency of Flu-M than combinations of DT-061 and a CaM inhibitor on MAPK-output and a strong effect on cell proliferation. While our study is limited, our results suggest that improved PTZ derivatives that retain both, their CaM inhibitory and PP2A activating properties, but have lost their neurological side-effects, may be interesting to pursue further as anti-cancer agents.