Targeting KRAS in Solid Tumors

CME

Accessing KRASG12C: A New Anticancer Approach

Physicians: Maximum of 0.75 AMA PRA Category 1 Credit

Released: October 29, 2020

Expiration: October 28, 2021

Marwan Fakih
Marwan Fakih, MD

Activity

Progress
1
Course Completed

References

  1. Hong D, Fakih, M, Strickler J, et al. KRASG12C inhibition with sotorasib in advanced solid tumors. N Engl J Med. 2020;383:1207-1217.
  2. Khan AQ, Kuttikrishnan S, Siveen KS, et al. RAS-mediated oncogenic signaling pathways in human malignancies. Semin Cancer Biol. 2019;54:1-13.
  3. Taieb J, Le Malicot K, Shi Q, et al. Prognostic value of BRAF and KRAS mutations in MSI and MSS stage III colon cancer. J Natl Cancer Inst. 2016;109:djw272.
  4. Holch J, Ricard I, Stintzing S, et al. The relevance of primary tumour location in patients with metastatic colorectal cancer: a meta-analysis of first-line clinical trials. Eur J Cancer. 2017;70:87-98.
  5. Kadota K, Sima CS, Arcila ME, et al. KRAS mutation is a significant prognostic factor in early-stage lung adenocarcinoma. Am J Surg Pathol. 2016;40:1579-1590.
  6. Zhang SM, Zhu QG, Ding XX, et al. Prognostic value of EGFR and KRAS in resected non-small cell lung cancer: a systematic review and meta-analysis. Cancer Manag Res. 2018;10:3393-3404.
  7. Fan G, Zhang K, Ding J, Li J. Prognostic value of EGFR and KRAS in circulating tumor DNA in patients with advanced non-small cell lung cancer: a systematic review and meta-analysis. Oncotarget. 2017;8:33922-33932.
  8. Muñoz-Maldonado C, Zimmer Y, Medová M. A comparative analysis of individual RAS mutations in cancer biology. Front Oncol. 2019;9:1088.
  9. Sanchez-Vega F, Mina M, Armenia J, et al. Oncogenic signaling pathways in The Cancer Genome Atlas. Cell. 2018;173:321-337.e310.
  10. McCormick F. Targeting KRAS directly. Ann Rev Cancer Biol. 2018;2:81-90.
  11. Ottaiano A, Normanno N, Facchini S, et al. Study of Ras mutations’ prognostic value in metastatic colorectal cancer: STORIA analysis. Cancers (Basel). 2020;12:1919.
  12. Fakih MG, Desai J, Kuboki Y, et al. CodeBreak 100: Activity of AMG 510, a novel small molecule inhibitor of KRASG12C, in patients with advanced colorectal cancer. Program and abstracts of the American Society of Clinical Oncology 2020 Virtual; May 29-31, 2020. Abstract 4018.
  13. Ou S-HI, Sokol ES, Madison R, et al. 92PD Comprehensive pan-cancer analysis of KRAS genomic alterations (GA) including potentially targetable subsets. Program and abstracts of European Society for Medical Oncology; September 27- October 1, 2010; Barcelona, Spain. Abstract 1433.
  14. Jӓnne P, Papadopoulos K, Ou I, et al. A phase 1 clinical trial evaluating the pharmacokinetics (PK), safety, and clinical activity of MRTX849, a mutant-selective small molecule KRAS G12C inhibitor, in advanced solid tumors. Program and abstracts of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; October 26-30, 2019; Boston, Massachusetts. Abstract CS5.
  15. Jӓnne PA, Rybkin II, Spira AI, et al. KRYSTAL-1: activity and safety of adagrasib (MRTX849) in advanced/metastatic non–small-cell lung cancer (NSCLC) harboring KRAS G12C mutation. Program and abstracts of the 32nd EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics; October 24-25, 2020. Abstract LBA-03.
  16. Johnson ML, Ou SH, Barve M, et al. AACR-NCI-EORTC 2020. KRYSTAL-1: activity and safety of adagrasib (MRTX849) in patients with colorectal cancer (CRC) and other solid tumors harboring a KRAS G12C mutation. Program and abstracts of the 32nd EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics; October 24-25, 2020. Abstract LBA4.
  17. Sholl LM, Aisner DL, Varella-Garcia M, et al. Multi-institutional oncogenic driver mutation analysis in lung adenocarcinoma: the Lung Cancer Mutation Consortium Experience. J Thorac Oncol. 2015;10:768-777.
  18. Jin C, Yeom SS, Koo B, et al. Rapid and accurate detection of KRAS mutations in colorectal cancers using the isothermal-based optical sensor for companion diagnostics. Oncotarget. 2017;8:83860-83871.
  19. Dong L, Wang S, Fu B, et al. Evaluation of droplet digital PCR and next generation sequencing for characterizing DNA reference material for KRAS mutation detection. Sci Rep. 2018;8:9650
  20. Hata AN, Shaw AT. Resistance looms for KRAS G12C inhibitors. Nat Med. 2020;26:169-170.
  21. Amodio V, Yaeger R, Arcella P, et al. EGFRA blockade reverts resistance to KRAS G12C inhibition in CRC. Cancer Discov. 2020;10:1129-1139.
  22. Hallin J, Engstrom LD, Hargis L, et al. The KRASG12C inhibitor MRTX849 provides insight toward therapeutic susceptibility of KRAS-mutant cancers in mouse models and patients. Cancer Discov. 2020;10:54-71.
  23. Fedele C, Ran H, Diskin B, et al. SHP2 inhibition prevents adaptive resistance to MEK inhibitors in multiple cancer models. Cancer Discov. 2018;8:1237-1249.
  24. Briere DM, Calinisan A, Aranda R, et al. The KRASG12C inhibitor MRTX849 reconditions the tumor immune microenvironment and leads to duragle complete responses in combination with anti-PD-1 therapy in a syngeneic mouse model. Program and abstracts of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; October 26-30, 2019; Boston, Massachusetts. Abstract LB-C09.
  25. Fakih MG, Durm GA, Govindan R, et al. Trial in progress: a phase Ib study of AMG 510, a specific and irreversible KRASG12C inhibitor, in combination with other anticancer therapies in patients with advanced solid tumors harboring KRAS p.G12C mutation (CodeBreak 101). Program and abstracts of the American Society of Clinical Oncology 2020 Virtual; May 29-31, 2020. Abstract TPS3661.
  26. ClinicalTrials.gov. Dose-escalation and dose-expansion of RMC-4630 and cobimetinib in relapsed/refractory solid tumors. Available at: https://clinicaltrials.gov/ct2/show/NCT03989115. Accessed October 20, 2020.
  27. Tran E, Robbins PF, Lu YC, et al. T-cell transfer therapy targeting mutant KRAS in cancer. N Engl J Med. 2016;375:2255-2262.