- |||||||||| 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.
- |||||||||| 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.
- |||||||||| 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.
- |||||||||| Avastin (bevacizumab) / Roche, Lumakras (sotorasib) / Amgen
Preclinical, Retrospective data, Review, Journal, Combination therapy, Checkpoint inhibition, IO biomarker, Metastases: Efficacy of first-line immune checkpoint inhibitor and anti-angiogenic agent combination therapy for Kirsten rat sarcoma viral antigen-mutant advanced non-small-cell lung cancer: a systematic review and network meta-analysis. (Pubmed Central) - Sep 2, 2024 The efficacy of Chemo?+?Bev?+?ICI is potentially high for improving PFS and OS in KRAS-mutant NSCLC. In advanced NSCLC, the presence or absence of KRAS mutations may need to be considered when administering first-line treatment.
- |||||||||| 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
- |||||||||| Lumakras (sotorasib) / Amgen
Retrospective data, Journal, Checkpoint inhibition, Real-world evidence, PD(L)-1 Biomarker, IO biomarker, Real-world, Metastases: Treatment patterns and outcomes in KRASG12C-positive advanced NSCLC patients previously treated with immune checkpoint inhibitors: A Canada-wide real-world, multi-center, retrospective cohort study. (Pubmed Central) - Aug 7, 2024 This study contributes valuable real-world data on KRASG12C-positive advanced NSCLC post-ICI treatment. The absence of a standard treatment sequencing post-ICI underscores the need for further investigation and consensus-building in the evolving landscape of KRASG12C-targeted therapies.
- |||||||||| 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.
- |||||||||| Vectibix (panitumumab) / Amgen, Lumakras (sotorasib) / Amgen, Mvasi (bevacizumab-awwb) / Daiichi Sankyo, Amgen, AbbVie
Enrollment open: CodeBreaK 301: Study of Sotorasib, Panitumumab and FOLFIRI Versus FOLFIRI With or Without Bevacizumab-awwb in Treatment-na (clinicaltrials.gov) - Jul 31, 2024 P3, N=450, Recruiting, Overall, PDP1 is underscored as a vital oncogenic driver and promising therapeutic target for KRAS mutant CRC. Not yet recruiting --> Recruiting
- |||||||||| 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
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) - Jul 22, 2024 P1/2, N=713, Active, not recruiting, The pharmaco-economic evidence generated from this study has significant implications not only for guiding the drug pricing of the upcoming sotorasib but also for determining the reimbursement ratio for its potential inclusion in the National Reimbursement Drugs List in the future. Trial completion date: Nov 2027 --> Apr 2028
- |||||||||| 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
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