Examining Targeted Oncology Approaches- KRAS, ERK and MTAPTicker(s): KURA, MRTX, AMGN, AGIO, BGNE
An oncologist with knowledge about the clinical trials of MRTX849 in NSCLC and CRC, KO-947 in MAPK Pathway Tumors, Lifirafenib and AG-270, in MTAP-Deleted Tumors
Please tell us about your clinical practice, background as an oncologist, and research in the space. Can you explain briefly the following targeted approaches: KRAS, ERK and MTAPAdded By: slingshot_insights
What makes KRAS mutations one of the most common oncogene mutations with no targeted treatment option?Added By: slingshot_insights
In a recent abstract, Mirati’s MRTX849 alone and in combination with an anti-PD-1 antibody decreased intra-tumoral immune-suppressive M2-polarized macrophages, M- and G-MDSCs and increased immune promoting M1-polarized macrophages, dendritic cells, and CD4 and NK T cells in CT26 KRASG12C tumors, resulting in anti-tumor adaptive immune response in mice. Could these datapoints show a possible efficacy in humans as well?
17 of 26 KRAS G12C Xenografts Showed >30% Regression with MRTX849 at 100mg/kg QD, best response being for pancreas. How do you interpret this data?Added By: slingshot_insights
Beigene’s Lifirafenib showed antitumor activity in preclinical models and in cancer patients with tumors harboring BRAF V600E mutations and non-V600E BRAF mutations,as well as KRAS/NRAS mutations, in which the dimeric form of RAF is implicated. In which patient circumstances would choosing Lifirafenib make sense?
In Kura’s KO-947 squamous cell carcinoma abstract, The 11q13 amplicon contains multiple potential oncogenes, including three (CCND1, ANO1, FADD) that are MAPK-associated, and the pleiotropic effects of concerted overexpression of these genes appears to drive 11q13-amplified SCC cells in to MAPK pathway (ERK) addiction. How does this compare to Beigene’s Lifirafenib?
In Agios’ AG-270 Phase 1 trial, Plasma SAM concentration decreased by 65-74% across doses of 50-200 mg once daily and 200 mg twice daily. 9 paired tumor biopsies by IHC showed decreases in levels of SDMA residues, consistent with inhibition of the methyltransferase PRMT5, downstream of MAT2A inhibition. How important are those findings in your opinion?
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