Novel HER3 Agents for EGFR Mutated NSCLC

CME

New Frontiers in Advanced EGFR-Mutated NSCLC Therapy: Targeting HER3 With Novel Agents

Physicians: Maximum of 0.75 AMA PRA Category 1 Credit

Released: December 17, 2024

Expiration: June 16, 2025

Karen Reckamp
Karen Reckamp, MD, MS
Helena Yu
Helena Yu, MD

Activity

Progress
1 2
Course Completed

References

  1. Cheng YI, Gan YC, Liu D, et al. Potential genetic modifiers for somatic EGFR mutation in lung cancer: a meta-analysis and literature review. BMC Cancer. 2019;19:1068.
  2. Osimertinib [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2024.
  3. Amivantamab-vmjw [prescribing information]. Horsham, PA: Janssen Biotech, Inc; 2024.
  4. Lakkunarajah S, Truong PT, Bone JN, et al. First-line osimertinib for patients with EGFR-mutated advanced non-small cell lung cancer: efficacy and safety during the COVID-19 pandemic. Transl Lung Cancer Res. 2023;12:1454-1465.
  5. Hsu R, Benjamin DJ. A narrative review of antibody-drug conjugates in EGFR-mutated non-small cell lung cancer. Front Oncol. 2023;13:1252652.
  6. Schoenfeld AJ, Chan JM, Kubota D, et al. Tumor analyses reveal squamous transformation and off-target alterations as early resistance mechanisms to first-line osimertinib in EGFR-mutant lung cancer. Clin Cancer Res. 2020;26:2654-2663.
  7. Chmielecki J, Gray JE, Cheng Y, et al. Candidate mechanisms of acquired resistance to first-line osimertinib in EGFR-mutated advanced non-small cell lung cancer. Nat Commun. 2023;14:1070.
  8. Iacovino M, Ciaramella V, Paragliola F, et al. Use of liquid biopsy in monitoring therapeutic resistance in EGFR oncogene addicted NSCLC. Explor Target Antitumor Ther. 2020;1:391-400.
  9. Ferro A, Marinato GM, Mulargiu C, et al. The study of primary and acquired resistance to first-line osimertinib to improve the outcome of EGFR-mutated advanced Non-small cell lung cancer patients: the challenge is open for new therapeutic strategies. Crit Rev Oncol Hematol. 2024;196:104295.
  10. Chen H, Lin Z, Arnst KE, et al. Tubulin inhibitor-based antibody-drug conjugates for cancer therapy. Molecules. 2017;22.
  11. Passiglia F, Bironzo P, Bertaglia V, et al. Optimizing the clinical management of EGFR-mutant advanced non-small cell lung cancer: a literature review. Transl Lung Cancer Res. 2022;11:935-949.
  12. Lu S, Kato T, Dong X, et al. Osimertinib after chemoradiotherapy in stage III EGFR-mutated NSCLC. N Engl J Med. 2024;391:585-597.
  13. Cho BC, Lu S, Felip E, et al. Amivantamab plus lazertinib in previously untreated EGFR-mutated advanced NSCLC. N Engl J Med. 2024;391:1486-1498.
  14. Christopoulos P, Kirchner M, Roeper J, et al. Risk stratification of EGFR(+) lung cancer diagnosed with panel-based next-generation sequencing. Lung Cancer. 2020;148:105-112.
  15. Desai A, Vazquez TA, Arce KM, et al. ctDNA for the evaluation and management of EGFR-mutant non-small cell lungcancer. Cancers (Basel). 2024;16.
  16. Yonesaka K. HER2-/HER3-targeting antibody-drug conjugates for treating lung and colorectal cancers resistant to EGFR inhibitors. Cancers (Basel). 2021;13.
  17. Chandarlapaty S, Sawai A, Scaltriti M, et al. AKT inhibition relieves feedback suppression of receptor tyrosine kinase expression and activity. Cancer Cell. 2011;19:58-71.
  18. Qin K, Hong L, Zhang J, Le X. MET amplification as a resistance driver to TKI therapies in lung cancer: Clinical challenges and opportunities. Cancers (Basel). 2023;15.
  19. Karachaliou N, Fernandez-Bruno M, Bracht JWP, et al. EGFR first- and second-generation TKIs-there is still place for them in EGFR-mutant NSCLC patients. Transl Cancer Res. 2019;8:S23-S47.
  20. Kogawa T, Yonemori K, Naito Y, et al. Phase 1/2, multicenter, non-randomized, open-label, multiple-dose first-in-human study of U3-1402 (anti-HER3 antibody drug conjugate) in subjects with HER3-positive metastatic breast cancer. Presented at: 2017 ASCO Annual Meeting; June 2-6, 2017. Abstract TPS1116.
  21. Santos ES, Kaplan B, Kirshner E, et al. Osimertinib for previously treated patients with advanced EGFR T790M mutation-positive NSCLC: Tolerability and diagnostic methods from an expanded access program. Oncol Ther. 2018;6:45-58.
  22. Lee J, Piotrowska Z, Soo R, et al. Combatting acquired resistance to osimertinib in EGFR-mutant lung cancer. Ther Adv Med Oncol. 2022;14:17588359221144099.
  23. Uliano J, Corvaja C, Curigliano G, Tarantino P. Targeting HER3 for cancer treatment: a new horizon for an old target. ESMO Open. 2023;8:100790.
  24. Shimizu T, Yonesaka K, Hayashi H, et al. Phase 1 study of new formulation of patritumab (U3-1287) Process 2, a fully human anti-HER3 monoclonal antibody in combination with erlotinib in Japanese patients with advanced non-small cell lung cancer. Cancer Chemother Pharmacol. 2017;79:489-495.
  25. Sequist LV, Gray JE, Harb WA, et al. Randomized phase II trial of seribantumab in combination with erlotinib in patients with EGFR wild-type non-small cell lung cancer. Oncologist. 2019;24:1095-1102.
  26. Peters C, Brown S. Antibody-drug conjugates as novel anti-cancer chemotherapeutics. Biosci Rep. 2015;35.
  27. Fu Z, Li S, Han S, et al. Antibody drug conjugate: the "biological missile" for targeted cancer therapy. Signal Transduct Target Ther. 2022;7:93.
  28. Dan N, Setua S, Kashyap VK, et al. Antibody-drug conjugates for cancer therapy: Chemistry to clinical implications. Pharmaceuticals (Basel). 2018;11.
  29. Hashimoto Y, Koyama K, Kamai Y, et al. A novel HER3-targeting antibody-drug conjugate, U3-1402, exhibits potent therapeutic efficacy through the delivery of cytotoxic payload by efficient internalization. Clin Cancer Res. 2019;25:7151-7161.
  30. Janne PA, Baik C, Su WC, et al. Efficacy and safety of patritumab deruxtecan (HER3-DXd) in EGFR inhibitor-resistant, EGFR-mutated non-small cell lung cancer. Cancer Discov. 2022;12:74-89.
  31. Hayashi H, Yu HA, Cail C, et al. First report of cohort 3 and extended follow-up data from the U31402-A-U102 study of HER3-DXd in EGFR-mutated NSCLC. Presented at: Japanese Society of Medical Oncology 2023; March 16-18, 2023. Abstract.
  32. Yu HA, Goto Y, Hayashi H, et al. HERTHENA-Lung01, a phase II trial of patritumab deruxtecan (HER3-DXd) in epidermal growth factor receptor-mutated non-small-cell lung cancer after epidermal growth factor receptor tyrosine kinase inhibitor therapy and platinum-based chemotherapy. J Clin Oncol. 2023;41:5363-5375.
  33. Yu HA, Goto Y, Hayashi H, et al. OA05.03 Patritumab deruxtecan (HER3-DXd) in EGFR-mutated NSCLC following EGFRTKI and platinum-based chemotherapy: HERTHENA-Lung01. J Thorac Oncol. 2023;18:S53-S54.
  34. Mok T, Janne PA, Nishio M, et al. HERTHENA-Lung02: phase III study of patritumab deruxtecan in advanced EGFR-mutated NSCLC after a third-generation EGFR TKI. Future Oncol. 2024;20:969-980.
  35. Zhang L, Ma Y, Zhao Y, et al. BL-B01D1, a first-in-class EGFRxHER3 bispecific antibody-drug conjugate, in patients with non-small cell lung cancer: updated results from first-in-human phase I study. Presented at: ESMO Congress; October 20-24, 2023. Abstract 1316MO.
  36. Ma Y, Huang Y, Zhao Y, et al. BL-B01D1, a first-in-class EGFR-HER3 bispecific antibody-drug conjugate, in patients with locally advanced or metastatic solid tumours: a first-in-human, open-label, multicentre, phase 1 study. Lancet Oncol. 2024;25:901-911.
  37. Zhou Q, Wu Y-L, Li J, et al. 658MO Phase I study of SHR-A2009, a HER3-targeted ADC, in advanced solid tumors. Ann Oncol. 2023;34:S463-S463.
  38. Araki T, Kanda S, Horinouchi H, Ohe Y. Current treatment strategies for EGFR-mutated non-small cell lung cancer: from first line to beyond osimertinib resistance. Jpn J Clin Oncol. 2023;53:547-561.