Lumakras (sotorasib) / Amgen 
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  • ||||||||||  Krazati (adagrasib) / BMS, Lumakras (sotorasib) / Amgen
    Journal:  Targeting ALDH1A1 to enhance the efficacy of KRAS-targeted therapy through ferroptosis. (Pubmed Central) -  Sep 24, 2024   
    Meanwhile, we established that GTF2I is dephosphorylated at S784 via ERK by KRAS inhibitors, which hinders its nuclear translocation and mediates ALDH1A1's upregulation in response to KRAS inhibitors. In summary, the results offer valuable insights into targeting ALDH1A1 to enhance the effectiveness of KRAS-targeted therapy through ferroptosis in cancer treatment.
  • ||||||||||  Krazati (adagrasib) / BMS, Lumakras (sotorasib) / Amgen
    Review, Journal:  Mechanisms of resistance to KRASG12C inhibitors in KRASG12C-mutated non-small cell lung cancer. (Pubmed Central) -  Sep 21, 2024   
    We highlight the lack of data on non-genomic resistance and the need for comprehensive clinical studies exploring histological, genomic, and non-genomic changes at resistance. This knowledge could help foster new treatment initiatives in this challenging context.
  • ||||||||||  Vectibix (panitumumab) / Amgen, Lumakras (sotorasib) / Amgen
    Sotorasib (soto), panitumumab (pani), and FOLFIRI in first-line (1L) KRAS G12C (Hall 404) -  Sep 17, 2024 - Abstract #ESMOAsia2024ESMO_Asia_215;    
    P1, P3
    Conclusions The combination of soto, pani, and FOLFIRI in the 1L setting had a tolerable safety profile and a promising response rate in pts from Japan and ROW. The phase III CodeBreaK 301 (NCT06252649) study is currently enrolling to evaluate this combination against standard of care in 1L mCRC.
  • ||||||||||  Lumakras (sotorasib) / Amgen
    Journal, Metastases:  Returning from the afterlife? Sotorasib treatment for advanced KRAS mutant lung cancer: A case report. (Pubmed Central) -  Sep 9, 2024   
    These findings provide additional evidence for the utility of single agent or combination regimens containing SMARCA2 PROTACs as synthetic lethal therapeutics against SMARCA4 mutant cancers. Sotorasib has shown promising clinical efficacy in patients with the KRAS G12c mutation and has no apparent toxic side effects.
  • ||||||||||  AMG 193 / Amgen
    Phase 1b Study of AMG 193, An MTA-Cooperative PRMT5i, Alone and in Combination with Other Therapies in MTAP-deleted NSCLC (Exhibit Hall) -  Sep 8, 2024 - Abstract #IASLCWCLC2024IASLC_WCLC_2887;    
    Subprotocol B (N ~ 94) will evaluate AMG 193 plus sotorasib in MTAP -deleted and KRAS G12C-mutated NSCLC...Patients will be required to have PD-L1-positive tumors in subprotocol A arm C, KRAS G12C-mutated tumors in subprotocol B, and active brain metastasis in subprotocol C. AMG 193 will be administered daily continuously. The study is expected to start recruitment in April 2024.
  • ||||||||||  Lumakras (sotorasib) / Amgen
    Long-Term Outcomes with Sotorasib in KRAS G12c-Mutated Advanced NSCLC from the Global Expanded Access Program (EAP) Study-436 (Exhibit Hall) -  Sep 8, 2024 - Abstract #IASLCWCLC2024IASLC_WCLC_2884;    
    50% 35 8.4 (6.0-12.7) 5.0 (3.4-6.5) Unknown/missing 10 11.8 (0.8-NE) 3.6 (0.8-24.3) *rwPFS was estimated based on time from start of sotorasib to end of protocol due to disease progression or death, any death before new anticancer therapy, or end of commercial sotorasib, whichever occurred earlier. CI, confidence interval; CNS, central nervous system; ECOG PS, Eastern Cooperative Oncology Group Performance Status; PD-L1, programmed death-ligand 1.
  • ||||||||||  Krazati (adagrasib) / BMS, Lumakras (sotorasib) / Amgen
    Review, Journal:  Structural insights into small-molecule KRAS inhibitors for targeting KRAS mutant cancers. (Pubmed Central) -  Sep 5, 2024   
    Structure-activity relationship (SAR) studies have been instrumental in optimizing the binding affinity, selectivity, and pharmacokinetic properties of these inhibitors, leading to the development of promising therapeutic agents like Sotorasib and Adagrasib. This review provides an overview of the KRAS pathway, KRAS binding sites, strategies for direct and indirect inhibition using small molecules, and SAR based on the co-crystal structures of inhibitors with KRAS mutants which is expected to offer new hope for patients with KRAS-driven cancers through the development of new KRAS-targeted drugs.
  • ||||||||||  Vectibix (panitumumab) / Amgen, Lumakras (sotorasib) / Amgen
    Journal, Metastases:  Combining EGFR and KRAS G12C Inhibitors for KRAS G12C Mutated Advanced Colorectal Cancer. (Pubmed Central) -  Aug 23, 2024   
    Based on these results, phase III clinical trials are being conducted to investigate EGFR and KRAS G12C inhibitor combinations as a first or second-line treatment for KRAS G12C mutated advanced CRC. Furthermore, other KRAS G12C inhibitors, KRAS G12D inhibitors, and pan-RAS inhibitors are being developed, which could make more patients with advanced CRC eligible for KRAS inhibition.
  • ||||||||||  Krazati (adagrasib) / BMS, Lumakras (sotorasib) / Amgen
    Review, Journal, Tumor mutational burden, PD(L)-1 Biomarker, IO biomarker:  Current perspectives of KRAS in non-small cell lung cancer. (Pubmed Central) -  Aug 15, 2024   
    To date, two G12C inhibitors have been FDA-approved, namely sotorasib and adagrasib. In this review, we summarize the different drug combinations used to target KRAS G12c, upcoming G12D inhibitors and novel therapies targeting KRAS.
  • ||||||||||  Lumakras (sotorasib) / Amgen
    Journal, Metastases:  Sotorasib (960 (Pubmed Central) -  Aug 10, 2024   
    P1/2
    In this review, we summarize the different drug combinations used to target KRAS G12c, upcoming G12D inhibitors and novel therapies targeting KRAS. Patients treated with sotorasib 960
  • ||||||||||  Krazati (adagrasib) / BMS, Lumakras (sotorasib) / Amgen
    Review, Journal, IO biomarker:  The next-generation KRAS inhibitors (Pubmed Central) -  Aug 7, 2024   
    Additionally, immunological approaches utilizing T-cell receptor (TCR)-engineered T cell therapy or vaccines, and Hapimmune antibodies are ongoing. This review delineates the recent advancements in KRAS inhibitor development in the post-sotorasib/adagrasib era, with a focus on NSCLC.
  • ||||||||||  RGT-018 / Regor
    Journal:  Discovery of RGT-018: a Potent, Selective and Orally Bioavailable SOS1 Inhibitor for KRAS-driven Cancers. (Pubmed Central) -  Aug 1, 2024   
    FDA-approved sotorasib and adagrasib provide breakthrough therapies for cancer patients with KRASG12C mutation...Further enhanced anti-proliferation activity was observed when RGT-018 was combined with MEK, KRASG12C, EGFR or CDK4/6 inhibitors...Furthermore, RGT-018 overcame the resistance to the approved KRASG12C inhibitors caused by clinically acquired KRAS mutations either as a single agent or in combination. RGT-018 displayed promising pharmacological properties for combination with targeted agents to treat a broader KRAS-driven patient population.
  • ||||||||||  Krazati (adagrasib) / BMS, Lumakras (sotorasib) / Amgen
    Cost-Effectiveness Analysis of Sotorasib vs. Adagrasib in KRAS G12c-Mutated Previously Treated NSCLC (Exhibit Hall) -  Jul 24, 2024 - Abstract #IASLCWCLC2024IASLC_WCLC_2349;    
    Despite uncertainty on relative OS and PFS outcomes, adagrasib was associated with higher costs to manage the higher adverse event burden. The higher costs of managing adverse events, including higher usage of medications and dose interruptions, led to sotorasib being more cost-effective than adagrasib.
  • ||||||||||  Krazati (adagrasib) / BMS, Lumakras (sotorasib) / Amgen
    KRASG12c-Mutant NSCLC Under Targeted Therapy in China: Lessons from Eight Cases (Exhibit Hall) -  Jul 24, 2024 - Abstract #IASLCWCLC2024IASLC_WCLC_2184;    
    Additionally, patients with KRAS G12C have a predilection to bone metastasis, which is consistent with the current literature. Larger prospective study on efficacy of KRASG12Ci will be needed to validate our findings and clarify the markers for further patient classification and stratification.
  • ||||||||||  Tagrisso (osimertinib) / AstraZeneca, Lumakras (sotorasib) / Amgen
    MALAT1 And NEAT1 Contribute to Adaptive Mutability in the Transition from Drug Tolerance to Drug Resistance in Lung Cancer (Exhibit Hall) -  Jul 24, 2024 - Abstract #IASLCWCLC2024IASLC_WCLC_1690;    
    This work has identified the lncRNAs MALAT1 and NEAT1 as potentially important molecules implicated in the development of acquired drug resistance that emerges from drug tolerance. Further studies are ongoing to determine whether modulating MALAT1 represents a potential approach to augment therapy in patients with lung adenocarcinomas undergoing treatment with targeted therapeutics.
  • ||||||||||  Lumakras (sotorasib) / Amgen
    Real-World Comparative Effectiveness of Sotorasib vs Docetaxel as 2L/2L+ Treatment of KRAS G12c-Mutated Advanced NSCLC (Exhibit Hall) -  Jul 24, 2024 - Abstract #IASLCWCLC2024IASLC_WCLC_1606;    
    3 6 (6%) 4 (6%) 7 (4%) 5 (4%) Not available 20 (20%) 12 (20%) 38 (23%) 27 (23%) Histology, n (%) 0.29 0.25 Non-squamous cell carcinoma 100 (98%) 55 (93%) 157 (96%) 113 (96%) Squamous cell carcinoma 2 (2%) 3 (5%) 2 (1%) 4 (3%) NSCLC histology NOS 0 (0%) 1 (2%) 5 (3%) 1 (1%) Most recent PD-L1 expression at baseline (tumor cell staining), n (%) 0.2 indicate inadequate balance; b Stage was not reported in 1 patient each for sotorasib and docetaxel in the 2L cohort, and in 6 sotorasib-treated patients vs 2 docetaxel-treated patients in the 2L+ cohort. Chemo, chemotherapy; ECOG PS, Eastern Cooperative Oncology Group performance status; NOS, not otherwise specified; NSCLC, non-small cell lung cancer; PD-L1, programmed cell death ligand 1; SD, standard deviation; SMD, standardized mean difference.
  • ||||||||||  Lumakras (sotorasib) / Amgen
    Delineating the Mechanism of Resistance to Targeted Therapy via Cellular Transdifferentiation (20D) -  Jul 24, 2024 - Abstract #IASLCWCLC2024IASLC_WCLC_1092;    
    Upon treatment with Sotorasib, tumors initially demonstrated slow tumor growth...Conclusions : We have developed a new experimental system and framework for the study of lung t-SCLC at the single-cell level. Ongoing work includes the integration of new resources to study lineage reprogramming, the regulation of transdifferentiation by the cancer genome, and advancing new therapeutic strategies that combat plasticity by deploying unique drug combinatorial strategies.
  • ||||||||||  Krazati (adagrasib) / BMS, Lumakras (sotorasib) / Amgen
    Journal:  Clinicopathological, molecular, and prognostic features of colorectal carcinomas with KRAS c.34G>T (p.G12C) mutation. (Pubmed Central) -  Jul 23, 2024   
    Among 1122 BRAF-wild-type colorectal carcinomas, compared with KRAS-wild-type tumors, multivariable-adjusted colorectal cancer-specific mortality hazard ratios (95% confidence interval) were 1.82 (1.05-3.17) in KRAS c.34G>T (p.G12C)-mutated tumors (p?=?0.035) and 1.57 (1.22-2.02) in other KRAS-mutated tumors (p?=?0.0004). Our study provides novel evidence for clinical and tumor characteristics of KRAS c.34G>T (p.G12C)-mutated colorectal carcinoma.
  • ||||||||||  Lumakras (sotorasib) / Amgen
    Journal:  Sotorasib in KRAS-Mutated Colorectal Cancer. Reply. (Pubmed Central) -  Jul 10, 2024   
    This study adds to the ongoing efforts to address the therapeutic hurdles presented by KRAS in cancer treatment. No abstract available