Lumakras (sotorasib) / Amgen 
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  • ||||||||||  Krazati (adagrasib) / Mirati, Lumakras (sotorasib) / Amgen
    Preclinical, Review, Journal, PD(L)-1 Biomarker, IO biomarker:  Targeted therapies for KRAS-mutant non-small cell lung cancer: from preclinical studies to clinical development-a narrative review. (Pubmed Central) -  Mar 10, 2023   
    Adagrasib, a highly selective covalent inhibitor of KRAS G12C, has also shown efficacy in pretreated patients and other novel KRAS inhibitors are being under evaluation in early-phase studies...The discovery of selective KRAS G12C inhibitors has changed the therapeutic scenario of KRAS G12C-mutant NSCLC. Various studies testing KRAS inhibitors in different settings of disease, as single-agent or in combination with targeted agents for synthetic lethality and immunotherapy, are currently ongoing in this molecularly-defined subgroup of patients to further improve clinical outcomes.
  • ||||||||||  Krazati (adagrasib) / Mirati, Lumakras (sotorasib) / Amgen
    Journal:  Understanding KRAS for better targeting. (Pubmed Central) -  Mar 10, 2023   
    Various studies testing KRAS inhibitors in different settings of disease, as single-agent or in combination with targeted agents for synthetic lethality and immunotherapy, are currently ongoing in this molecularly-defined subgroup of patients to further improve clinical outcomes. No abstract available
  • ||||||||||  Krazati (adagrasib) / Mirati, Lumakras (sotorasib) / Amgen
    Journal:  Multiple initiatives to conquer KRAS G12C inhibitor resistance from the perspective of clinical therapy. (Pubmed Central) -  Mar 9, 2023   
    It is essential to improve the therapeutic effect and achieve long-term disease control through accumulating rapid exploration of drug resistance mechanisms in preclinical trials and developing rational combination dosing approaches from clinical practice. Our presentation of the perspective provides insights into drug resistance in this groundbreaking area of research.
  • ||||||||||  Krazati (adagrasib) / Mirati, Lumakras (sotorasib) / Amgen
    Review, Journal:  Targeting KRAS in colorectal cancer: the beginning of a new era. (Pubmed Central) -  Mar 7, 2023   
    Consequently, novel combinatory strategies to disrupt the RAS signaling pathways are under clinical investigation. This review aims to discuss the current knowledge and novel routes of KRAS inhibition in metastatic colorectal cancer.
  • ||||||||||  Lumakras (sotorasib) / Amgen
    Journal:  Analysis of KRAS-Ligand Interaction Modes and Flexibilities Reveals the Binding Characteristics. (Pubmed Central) -  Mar 2, 2023   
    After four decades of effort, one allosteric KRAS drug (Sotorasib) has been approved, inspiring more KRAS-targeted drug research...Finally, the flexibility of the three distinct binding sites to accommodate different potential ligands, based on MD simulation, is discussed. Collectively, these findings are intended to facilitate rational KRAS drug design.
  • ||||||||||  Krazati (adagrasib) / Mirati, Lumakras (sotorasib) / Amgen
    Review, Journal:  Annual review of KRAS inhibitors in 2022. (Pubmed Central) -  Feb 27, 2023   
    In this review, we overviewed the research progress of KRAS inhibitors with the potential to treat cancers covering articles published in 2022. The design strategies, discovery processes, structure-activity relationship (SAR) studies, cocrystal structure analysis as well as in vitro and in vivo activity were highlighted with the aim of providing updated sight to accelerate the further development of more potent inhibitors targeting various mutated-KRAS with favorable drug-like properties.
  • ||||||||||  sepantronium bromide (PC-002) / Cothera Biosci, Lumakras (sotorasib) / Amgen
    Journal:  Oncogenic RAS promotes MYC protein stability by upregulating the expression of the inhibitor of apoptosis protein (IAP) family member Survivin. (Pubmed Central) -  Feb 27, 2023   
    This discovery stemmed from our finding that Survivin expression is downregulated upon treatment of pancreatic cancer cells with the KRAS inhibitor Sotorasib...CIP2A, by inhibiting protein phosphatase 2A (PP2A), helps to maintain MYC phosphorylation at Ser 62, thereby ensuring its cooperation with oncogenic KRAS in driving cancer progression. Overall, these findings highlight a novel role for Survivin in mediating the cooperative actions of KRAS and MYC during malignant transformation and raise the possibility that targeting Survivin may offer therapeutic benefits against KRAS-driven cancers.
  • ||||||||||  Lumakras (sotorasib) / Amgen
    Case #1 (Walter E. Washington Convention Center, Ballroom C (Level 3)) -  Feb 27, 2023 - Abstract #ATS2023ATS_334;    
    P=N/A
    In the first report of survival in an EAP pt population treated with sotorasib, the median OS was similar to that observed in trials. The difference in median OS was minimal in pts with or without a history of CNS metastases at baseline.
  • ||||||||||  Lumakras (sotorasib) / Amgen
    Journal:  Global profiling of AMG510 modified proteins identified tumor suppressor KEAP1 as an off-target. (Pubmed Central) -  Feb 24, 2023   
    Moreover, AMG510 modified KEAP1 cys288 and induced NRF2 accumulation in the nuclear of NSCLC cells independent of KRAS/G12C mutation. Our study provides a comprehensive resource of protein off-targets of AMG510 and elucidates potential toxicological sideeffects for this covalent KRASG12C inhibitor.
  • ||||||||||  Lumakras (sotorasib) / Amgen
    Discovery of novel MAP4K4/MLK3 dual inhibitor for pancreatic cancer (PDAC) (Hall F-H (Indiana Convention Center)) -  Feb 14, 2023 - Abstract #ACSSp2023ACS_SP_12239;    
    PDAC standard-of-care chemotherapies include FOLFIRINOX, Gemcitabine, and Abraxane...The KRAS mutation is universal in PDAC, and recently a small molecule therapeutic, Sotorasib, targeting the KRAS G12C mutant protein was approved for non-small cell lung cancer (NSCLC) harboring the G12C mutation; however, only 50% of patients respond and the majority of patients develop resistance...Herein, we describe progress towards the development of MAP4K4/MLK3 dual inhibitor, DYMM-003 which represents an effective molecular probe to study the role of MAP4K4 and MLK3 and continued development for improved treatments of PDAC. The synthesis, binding assays, and inhibition assays for the new analogs will be presented.
  • ||||||||||  Lumakras (sotorasib) / Amgen
    Process innovation to enable the scalable manufacture of sotorasib (Room 202 (Indiana Convention Center)) -  Feb 14, 2023 - Abstract #ACSSp2023ACS_SP_8412;    
    The enhanced process knowledge obtained from this effort further ensures the process robustness. Finally, by leveraging advanced PAT tools, the process efficiency and cycle time are significantly improved by addressing a previously problematic isolation process through systematic optimization of crystallization.
  • ||||||||||  Krazati (adagrasib) / Mirati, Lumakras (sotorasib) / Amgen
    Journal, IO biomarker:  Current status and outlook of medical treatment for KRAS-mutated non-small cell lung cancer (Pubmed Central) -  Feb 13, 2023   
    In recent years, studies on the therapeutic efficacy of immune checkpoint inhibitors for KRAS-mutated NSCLC have made some progress. In this review, we systematically introduce the basic understanding of RAS gene and clinical characteristics of KRAS mutated NSCLC patients, summarize the medical treatments for KRAS mutated NSCLC, including chemotherapy, anti-vascular drug therapy and tumor immunotherapy, and focus on the review and outlook of the research progress of KRAS targeted therapy.
  • ||||||||||  Lumakras (sotorasib) / Amgen
    Sotorasib👎🏻 (Twitter) -  Feb 12, 2023   
  • ||||||||||  Lumakras (sotorasib) / Amgen
    Patient-reported outcomes from the CodeBreaK 200 phase 3 trial comparing sotorasib versus docetaxel in KRAS G12C-mutated NSCLC (Auditorium 1) -  Feb 10, 2023 - Abstract #ELCC2023ELCC_277;    
    P3
    Conclusions Patients treated with sotorasib reported less severe symptoms than those treated with docetaxel; hence, their daily lives were positively affected. In addition to improving clinical efficacy outcomes, sotorasib maintained QOL versus docetaxel suggesting that sotorasib may be a more tolerable treatment option for patients with pretreated, KRAS G12C -mutated advanced NSCLC.
  • ||||||||||  Lumakras (sotorasib) / Amgen
    Trial completion date, Trial primary completion date, Monotherapy:  CodeBreak101: Sotorasib Activity in Subjects With Advanced Solid Tumors With KRAS p.G12C Mutation (CodeBreak 101) (clinicaltrials.gov) -  Feb 9, 2023   
    P1b/2,  N=1143, Recruiting, 
    In addition to improving clinical efficacy outcomes, sotorasib maintained QOL versus docetaxel suggesting that sotorasib may be a more tolerable treatment option for patients with pretreated, KRAS G12C -mutated advanced NSCLC. Trial completion date: Jun 2027 --> Apr 2028 | Trial primary completion date: Dec 2024 --> Feb 2026
  • ||||||||||  Krazati (adagrasib) / Mirati, Lumakras (sotorasib) / Amgen
    Review, Journal:  Precision oncology provides opportunities for targeting KRAS-inhibitor resistance. (Pubmed Central) -  Feb 9, 2023   
    Redundancies within the KRAS signaling pathways and cross-talk between these pathways - as well as other canonical cancer-driving mechanisms - not only provide challenges but also present opportunities for drug development and targeted approaches. We discuss the challenges for the duality of KRAS inhibitor drug resistance with an additional focus on nongenetic mechanisms and the potential for patient-centered combination treatments.