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KRAS G12C NSCLC

CME

Research Focus in Advanced NSCLC: Emerging Insights on Next-Generation KRAS G12C Inhibitors

Physicians: Maximum of 0.75 AMA PRA Category 1 Credit

Released: April 30, 2026

Expiration: October 29, 2026

Activity

Progress
1 2 3
Course Completed

References

  1. Nadal E, Chaft J, Garassino M, et al. SUNRAY-02: a phase 3 study of olomorasib and immunotherapy in stage II-III KRAS G12C-mutant NSCLC after definitive therapy. Journal of Thoracic Oncology. 2025;20:S548. 
  2. Tan AC, Tan DS. Targeted therapies for lung cancer patients with oncogenic driver molecular alterations. J Clin Oncol. 2022;40:611-625.
  3. Riedl JM, Matsubara H, McNeil R, et al. Emerging landscape of KRAS inhibitors in cancer treatment. Cancer Cell. 2026;44:471-497.
  4. Yu HA, Sima CS, Shen R, et al. Prognostic impact of KRAS mutation subtypes in 677 patients with metastatic lung adenocarcinomas. J Thorac Oncol. 2015;10:431-437.
  5. Cascetta P, Marinello A, Lazzari C, et al. KRAS in NSCLC: state of the art and future perspectives. Cancers (Basel). 2022;14:5430.
  6. Ghazali N, Garassino MC, Leighl NB, et al. Immunotherapy in advanced, KRAS G12C-mutant non-small-cell lung cancer: current strategies and future directions. Ther Adv Med Oncol. 2025;17:17588359251323985.
  7. Ricciuti B, Arbour KC, Lin JJ, et al. Diminished efficacy of programmed death-(ligand)1 inhibition in STK11- and KEAP1-mutant lung adenocarcinoma is affected by KRAS mutation status. J Thorac Oncol. 2022;17:399-410.
  8. Skoulidis F, Goldberg ME, Greenawalt DM, et al. STK11/LKB1 mutations and PD-1 inhibitor resistance in KRAS-mutant lung adenocarcinoma. Cancer Discov. 2018;8:822-835.
  9. Sotorasib [prescribing information]. Thousand Oaks, CA: Amgen Inc.; 2025.
  10. Adagrasib [prescribing information]. Princeton, NJ: Bristol-Myers Squibb Company; 2026.
  11. Dy GK, Govindan R, Velcheti GS, et al. Long-term outcomes and molecular correlates of sotorasib efficacy in patients with pretreated KRAS G12C-mutated non–small-cell lung cancer: 2-year analysis of CodeBreaK 100. J Clin Oncol. 2023;41:3311-3317.
  12. Gadgeel S, Janne PA, Spira AI, et al. Two-year follow-up of adagrasib (MRTX849) monotherapy in patients with advanced/metastatic KRASG12C-mutated NSCLC. J Thorac Oncol. 2023;18:S118.
  13. de Langen AJ, Johnson ML, Mazieres J, et al. Sotorasib versus docetaxel for previously treated non-small-cell lung cancer with KRASG12C mutation: a randomised, open-label, phase 3 trial. Lancet. 2023;401:733-746.
  14. Barlesi F, Yao W, Duruisseaux M, et al. Adagrasib versus docetaxel in KRASG12C-mutated non-small-cell lung cancer (KRYSTAL-12): a randomised, open-label, phase 3 trial. Lancet. 2025;406:615-626.
  15. Luo J, Ostrem J, Pellini B, et al. Overcoming KRAS-mutant lung cancer. Am Soc Clin Oncol Educ Book. 2022;42:700-710.
  16. Di Federico A, Ricciotti I, Favorito V, et al. Resistance to KRAS G12C inhibition in non-small cell lung cancer. Curr Oncol Rep. 2023;25:1017-1029.
  17. Gregorc V, Majem M, Lo Russo G, et al.Fulzerasib plus cetuximab in first-line KRASG12C-mutated non-small-cell lung cancer (KROCUS): a single-arm, multicentre, phase 1b/2 trial. Lancet Oncol. 2026;27:432-441.
  18. Attili I, Corvaja C, Trillo Aliaga P, et al. Dealing with KRAS G12C inhibition in non-small cell lung cancer (NSCLC) - biology, clinical results and future directions. Cancer Treat Rev. 2025;137:102957.
  19. Li BT, Clarke JM, Felip E, et al. Sotorasib plus carboplatin and pemetrexed in KRAS G12C advanced NSCLC: updated analysis from the international CodeBreaK 101 trial. J Clin Oncol. 2024;42:8512-8512.
  20. Janne PA, Theelen W, Garassino MC, et al. First-line adagrasib (ADA) with pembrolizumab (PEMBRO) in patients (pts) with advanced/metastatic KRASG12C-mutated non-small cell lung cancer (NSCLC) from the phase 2 portion of the KRYSTAL-7 study. J Clin Oncol. 2025;43(16 suppl):8500.
  21. Garassino M, Jänne P, Barlesi F, et al. KRYSTAL-7: A phase III study of first-line adagrasib plus pembrolizumab versus pembrolizumab alone in patients with advanced NSCLC with KRASG12C mutation. Ann Oncol. 2024;35:S872-S873.
  22. Clarke J, Yaeger R, Felip E, et al. Overall survival (OS) with sotorasib plus carboplatin and pemetrexed in KRAS G12C-mutated advanced non-small cell lung cancer (NSCLC) from the global phase Ib CodeBreaK 101 study. Ann Oncol. 2025;36:S1057-S1058.
  23. Yoshioka H, Akamatsu H, Sakata S, et al. Final analysis of SCARLET study: A single-arm, phase II study of sotorasib plus carboplatin-pemetrexed in patients with advanced non-squamous, non-small cell lung cancer KRAS G12C mutation. J Clin Oncol. 2024;42(16 suppl):8616.
  24. Barlesi F, Felip E, Popat S, et al. Sotorasib versus pembrolizumab in combination with platinum doublet chemotherapy as first-line treatment for metastatic or locally advanced, PD-L1 negative, KRAS G12C-mutated NSCLC (CodeBreaK 202). J Clin Oncol. 2024;42(16 suppl):TPS8653.
  25. Zhang F, Wang B, Wu M, et al. Current status of KRAS G12C inhibitors in NSCLC and the potential for combination with anti-PD-(L)1 therapy: a systematic review. Front Immunol. 2025;16:1509173.
  26. Kim S, Chen J, Cheng T, et al. PubChem 2025 update. Nucleic Acids Res. 2025;53:D1516-D1525.
  27. Sacher AG, Miller WH Jr, Patel MR, et al. Single-agent divarasib in patients with KRAS G12C-positive non-small cell lung cancer: long-term follow-up of a phase I study. J Clin Oncol. 2025;43:3249-3253.
  28. Murciano-Goroff YR, Hollebecque A, Heist RS, et al. Pan-tumor activity of olomorasib, a next-generation KRAS G12C inhibitor in KRAS G12C-mutant advanced solid tumors: a first-in-human study. Nat Commun. 2026;[Epub ahead of print].
  29. Sacher AG, Sendur M, Stathis A, et al. MK-1084 for KRAS G12C-mutated (mut) metastatic non–small-cell lung cancer (mNSCLC): results from KANDLELIT-001. J Clin Oncol. 2025;43(16 suppl):8605.
  30. Wu YL, Zhou Q, Huang D, et al. Efficacy and safety of fulzerasib in patients (pts) with KRAS G12C-mutant non-small cell lung cancer (NSCLC): Updated results from phase I/II studies. Ann Oncol. 2025;36(2 suppl):S1056.
  31. Zhong J, Zhao J, Duan J, et al. Glecirasib plus sitneprotafib in patients with KRASG12C-mutated non-small-cell lung cancer in China: an open-label, multicentre, single-arm, phase 1/2a trial. Lancet Respir Med. 2026;14:163-173.
  32. Song Z, Li Z, Zhang Y, et al. Garsorasib in patients with KRAS G12C-mutated non-small-cell lung cancer: A pooled analysis of phase 1/2 study. Eur J Cancer. 2026;232:116153.
  33. Burns TF, Ammakkanavar NR, Hollebecque A, et al. Efficacy and safety of olomorasib in combination with pembrolizumab in treatment of patients with KRAS G12C-mutant advanced NSCLC. J Thorac Oncol. 2026;21:103528.
  34. Sacher A, Miller Jr WH, Paz-Ares L, et al. Divarasib single-agent long-term follow-up and atezolizumab combination treatment in patients with KRAS G12C-positive NSCLC. Presented at: 2024 World Conference on Lung Cancer; September 7-10, 2024. Abstract OA14.06.
  35. Sacher AG, Rottenberg Y, Kwiakowski M, et al. Updated results for MK-1084 + pembrolizumab in KRAS G12C-mutated (mut) metastatic non-small cell lung cancer (mNSCLC) enrolled in KANDLELIT-001. Presented at: 2026 European Lung Cancer Conference; March 25-28, 2026. Abstract 4MO.
  36. Skoulidis F, Soloman BJ, Frost NS, et al. Krascendo 2: A phase III study of divarasib and pembrolizumab vs pembrolizumab and chemotherapy in patients with previously untreated, advanced or metastatic, KRAS G12C-mutated non-small cell lung cancer (NSCLC). J Clin Oncol. 2025;43(suppl 16):TPS8656.
  37. Negrao MV, Arbour KC, Burns TF, et al. SUNRAY-01, a pivotal, global study of olomorasib (LY3537982) in combination with pembrolizumab with or without chemotherapy for 1L treatment in KRAS G12C-mutant advanced NSCLC. J Clin Oncol. 2024;42(suppl 16):TPS8649.
  38. Majem M, Gregorc V, Lo Russo G, et al. First-line (1L) fulzerasib + cetuximab in KRAS G12Cm advanced NSCLC: updated efficacy and safety from KROCUS study. Presented at: 2025 European Lung Cancer Conference; March 26-29, 2025. Abstract LBA1.
  39. Zhao J, Fang J, Yu Y, et al. Updated safety and efficacy data of combined KRAS G12C inhibitor (glecirasib, JAB-21822) and SHP2 inhibitor (JAB-3312) in patients with KRAS p.G12C mutated solid tumors. J Clin Oncol. 2024;42(16 suppl):3008.
  40. Spicer J, Blais N, Owen S, et al. A phase II study of neoadjuvant opnurasib KRAS G12C inhibitor in patients with surgically resectable non-small cell lung cancer (CCTG IND.242A): a substudy of the IND.242 Platform Master Protocol. Clin Lung Cancer. 2025;26:146-151.
  41. Pellini B, Bigot F, Janne P, et al. Efficacy and safety of elironrasib, a RAS(ON) G12C-selective inhibitor, in patients with KRAS G12C NSCLC following treatment with a KRAS(OFF) G12C inhibitor. Presented at: 2025 American Association for Cancer Research Annual Meeting; April 25-30, 2025. Abstract LB-B024.
  42. Punekar SR, Hong DS, Luo J, et al. Safety and clinical activity of daraxonrasib (RMC-6236) in RAS mutant non-small cell lung cancer (NSCLC). Presented at: 2025 European Lung Cancer Conference; March 26-29, 2025. Abstract 6MO.
  43. Skoulidis F, Arbour K, Popat S, et al. Trial in progress - RASolve 301: a phase 3 study of daraxonrasib (RMC-6236) vs. docetaxel in in patients with previously treated RAS mutant NSCLC. J Thorac Oncol. 2025;20:S573-S574.