- |||||||||| Lumakras (sotorasib) / Amgen
Review, Journal: Drugging the Undruggable: Advances on RAS Targeting in Cancer. (Pubmed Central) - Sep 23, 2021 Currently seven KRAS-G12C inhibitors are in clinical trials and sotorasib has become the first one to be granted FDA approval...We also review pre-clinical and clinical evidence for the efficacy of KRAS-G12C inhibitor monotherapy followed by an illustration of combination therapies designed to overcome primary resistance and extend durability of response. Finally, we briefly discuss novel approaches to targeting non-G12C mutant isoforms.
- |||||||||| Lumakras (sotorasib) / Amgen
Journal: Sotorasib effective in KRAS-mutant NSCLC. (Pubmed Central) - Sep 15, 2021 Finally, we briefly discuss novel approaches to targeting non-G12C mutant isoforms. No abstract available
- |||||||||| adagrasib (MRTX849) / Mirati, Lumakras (sotorasib) / Amgen
Journal, Combination therapy: Cytotoxic activity of KRAS inhibitors in combination with chemotherapeutics. (Pubmed Central) - Sep 15, 2021 Inhibition of downstream signaling cascades increases toxicity and other combinations exploited comprise G12C-directed inhibitors with SOS1 inhibitors, glucose/glutamine metabolic modulators, classical chemotherapeutics and others. The most suitable inhibitor combinations corroborated in preclinical development await clinical verification.
- |||||||||| Lumakras (sotorasib) / Amgen
Clinical, Journal: KRAS G12C Metastatic Colorectal Cancer: Specific Features of a New Emerging Target Population. (Pubmed Central) - Sep 8, 2021 The most suitable inhibitor combinations corroborated in preclinical development await clinical verification. The knowledge of the distinctive traits of KRAS G12C-mutated CRC patients is crucial to future translational research studies, clinical trial design, and proper interpretation of results.
- |||||||||| adagrasib (MRTX849) / Mirati, Lumakras (sotorasib) / Amgen
Review, Journal, IO biomarker: Targeting KRAS in non-small cell lung cancer: recent progress and new approaches. (Pubmed Central) - Sep 5, 2021 In previously treated patients with KRAS-mutant NSCLC, clinical activity has been shown for both sotorasib or adagrasib monotherapy; these data suggest promising new treatment options are on the horizon. With the stage now set for a new era in the treatment of KRAS-mutated NSCLC, many questions remain to be answered in order to further elucidate the mechanisms of resistance, how best to use combination strategies, and if KRAS inhibitors will have suitable activity in earlier lines of therapy for patients with advanced/metastatic NSCLC.
- |||||||||| Lumakras (sotorasib) / Amgen
Trial completion date, Trial primary 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) - Sep 2, 2021 P1/2, N=733, Recruiting, With the stage now set for a new era in the treatment of KRAS-mutated NSCLC, many questions remain to be answered in order to further elucidate the mechanisms of resistance, how best to use combination strategies, and if KRAS inhibitors will have suitable activity in earlier lines of therapy for patients with advanced/metastatic NSCLC. Trial completion date: Mar 2025 --> Jan 2026 | Trial primary completion date: Mar 2025 --> Jan 2026
- |||||||||| Lumakras (sotorasib) / Amgen
[VIRTUAL] KRAS G12C mutated lung adenocarcinomas: a morphological and molecular cartography () - Aug 29, 2021 - Abstract #ECP2021ECP_1176; KRAS G12C mutated LUADs represent a particular subtype characterized by a high inflammatory infiltrate, a relatively low PD-L1 positivity and a complex molecular profile with intricate interaction with various genes including STK11. A more in-depth characterization of the tumour histology, surrounding microenviron- ment and molecular profile of this specific subtype of LUAD could be useful to better select the patients that could benefit from novel targeted therapies to achieve the best treatment response.
- |||||||||| Lumakras (sotorasib) / Amgen
Review, Journal, IO biomarker: On target: Rational approaches to KRAS inhibition for treatment of non-small cell lung carcinoma. (Pubmed Central) - Aug 22, 2021 This review examines the role of KRAS mutations in NSCLC and the challenges in targeting KRAS. Based on specific KRAS biology, it reports exciting progress, exploring the use of novel direct KRAS inhibitors as monotherapy or in combination with other targeted therapies, chemotherapy, and immunotherapy.
- |||||||||| Lumakras (sotorasib) / Amgen
[VIRTUAL] Atom by atom: Inventing innovative medicines (Room: Zoom Room 27) - Aug 13, 2021 - Abstract #ACSFall2021ACS_Fall_7158; This lecture commemorating the 2021 Philip S. Portoghese Medicinal Chemistry Lectureship will highlight the invention of AMG 510 (sotorasib), now known as LUMAKRAS™, which recently received FDA approval for treating patients with advanced non-small cell lung cancer harboring the KRAS G12C mutation. An inside look at the path that led to drugging this previously “undruggable” target will be discussed, as well as both pre-clinical and clinical findings.
- |||||||||| adagrasib (MRTX849) / Mirati, Lumakras (sotorasib) / Amgen
Journal: Inhibition of RAS: proven and potential vulnerabilities. (Pubmed Central) - Aug 11, 2021 Thus, there remains an unmet need to identify more broadly efficacious RAS inhibitors. Here, we will discuss the current state of RAS(G12C) inhibitors and the potential for inhibiting additional RAS mutants through targeting RAS dimerization which has emerged as an important step in the allosteric regulation of RAS function.
- |||||||||| [VIRTUAL] Dual RAF/MEK Inhibitor VS - 6766 for Treatment of KRAS Mutant NSCLC: Novel Combinations Targeting G12C or G12V Variants (ePoster Hall) - Aug 9, 2021 - Abstract #IASLCWCLC2021IASLC_WCLC_856;
P2 Whereas G12C inhibitors (G12Ci) sotorasib (AMG 510) and adagrasib (MRTX849) have demonstrated promising antitumor activity in patients with KRAS G12C mutant (mt) NSCLC, KRAS G12V mt NSCLC remains an unmet need...In KRAS G12C mt NSCLC xenograft models (H2122, H358), combination with VS-6766 (0.3 mg/kg QD) augmented tumor growth inhibition by sotorasib, whereas trametinib (0.3 mg/kg QD) was much less effective in augmenting sotorasib efficacy...Furthermore, this combination regimen of VS-6766 with defactinib exhibited a manageable safety profile with no patients discontinuing for adverse events (Krebs AACR 2021). Conclusion These results support the ongoing registration-directed study evaluating VS-6766 ± defactinib for treatment of recurrent KRAS G12V mt NSCLC (NCT04620330) and provide rationale for the clinical evaluation of VS-6766 in combination with a G12C inhibitor for treatment of KRAS G12C mt NSCLC.
- |||||||||| Lumakras (sotorasib) / Amgen
Enrollment closed, Enrollment change, Metastases: AMG 510 Ethnic Sensitivity Study (CodeBreaK 105). (clinicaltrials.gov) - Aug 9, 2021 P1, N=12, Active, not recruiting, These findings warrant further investigation of the longitudinal cfDNA dynamics in patients receiving sotorasib. Recruiting --> Active, not recruiting | N=18 --> 12
- |||||||||| Tagrisso (osimertinib) / AstraZeneca, Lumakras (sotorasib) / Amgen
Clinical, Journal: Inhibitors Targeting CDK9 Show High Efficacy against Osimertinib and AMG510 Resistant Lung Adenocarcinoma Cells. (Pubmed Central) - Aug 8, 2021 CDK9 inhibitors could also significantly reduce the growth and viability of lung cancer organoids with high potency. Taken together, the data presented here strongly suggest that CDK9 inhibitors would be efficacious against K-Ras mutant and EGFR mutant NSCLCs, including those that develop resistance to targeted therapies.
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