Targeting DLL3 in ES-SCLC

CME

Future Applications in ES-SCLC: Targeting DLL3 and Emerging Evidence for T-Cell Engagers

Physicians: Maximum of 1.00 AMA PRA Category 1 Credit

Released: November 07, 2024

Expiration: May 06, 2025

Carl M. Gay
Carl M. Gay, MD, PhD

Activity

Progress
1 2
Course Completed

References

  1. Howlader N, Noone AM, Krapcho M, et al. SEER Cancer Statistics Review, 1975-2014, National Cancer Institute. seer.cancer.gov/archive/csr/1975_2014/index.html. Accessed November 5, 2024.
  2. Oronsky B, Reid TR, Oronsky A, et al. What’s new in SCLC? A review. Neoplasia. 2017;19:842-847.
  3. Alvarado-Luna G, Morales-Espinosa D. Treatment for small cell lung cancer, where are we now?-a review. Transl Lung Cancer Res. 2016;5:26-38.
  4. Rudin CM, Brambilla E, Faivre-Finn C, et al. Small-cell lung cancer. Nat Rev Dis Primers. 2021;7:3.
  5. Trigo J, Subbiah V, Besse B, et al. Lurbinectedin as second-line treatment for patients with small-cell lung cancer: a single-arm, open-label, phase 2 basket trial. Lancet Oncol. 2020;21:645-654.
  6. von Pawel J, Schiller JH, Shepherd FA, et al. Topotecan versus cyclophosphamide, doxorubicin, and vincristine for the treatment of recurrent small-cell lung cancer. J Clin Oncol. 1999;17:658-667.
  7. Yao J, Bergsland E, Aggarwal R, et al. DLL3 as an emerging target for the treatment of neuroendocrine neoplasms. Oncologist. 2022;27:940-951.
  8. Leonetti A, Facchinetti F, Minari R, et al. Notch pathway in small-cell lung cancer: from preclinical evidence to therapeutic challenges. Cell Oncol (Dordr). 2019;42:261-273.
  9. Sahlgren C, Lendahl U. Notch signaling and its integration with other signaling mechanisms. Regen Med. 2006;1:195-205. 
  10. Saunders LR, Bankovich AJ, Anderson WC, et al. A DLL3-targeted antibody-drug conjugate eradicates high-grade pulmonary neuroendocrine tumor-initiating cells in vivo. Sci Transl Med. 2015;7:302ra136.
  11. Owen DH, Giffin MJ, Bailis JM, et al. DLL3: an emerging target in small cell lung cancer. J Hematol Oncol. 2019;12:61. 
  12. Giffin MJ, Cooke K, Lobenhofer EK, et al. AMG 757, a half-life extended, DLL3-targeted bispecific T-cell engager, shows high potency and sensitivity in preclinical models of small-cell lung cancer. Clin Cancer Res. 2021;27:1526-1537.
  13. Rudin CM, Reck M, Johnson ML, et al. Emerging therapies targeting the delta-like ligand 3 (DLL3) in small cell lung cancer. J Hematol Oncol. 2023;16:66.
  14. Su PL, Chakravarthy K, Furuya N, et al. DLL3-guided therapies in small-cell lung cancer: from antibody-drug conjugate to precision immunotherapy and radioimmunotherapy. Mol Cancer. 2024;23:97.
  15. Ahn MJ, Cho BC, Felip E, et al. Tarlatamab for patients with previously treated small-cell lung cancer. N Engl J Med. 2023;389:2063-2075.
  16. Oin A, Kalemkerian GP. Treatment options for relapsed small-cell lung cancer: what progress have we made? J Oncol Pract. 2018;14:369.
  17. Sands J, Cho BC, Ahn MJ, et al. Tarlatamab sustained clinical benefit and safety in previously treated SCLC: DeLLphi-301 phase 2 extended follow-up. Presented at: 2024 World Conference on Lung Cancer; September 7-10, 2024. Abstract OA10.03.
  18. National Comprehensive Cancer Network. Clinical practice guidelines in oncology: small cell lung cancer. v.3.2025. nccn.org. Accessed November 5, 2024.
  19. Wermke M, Kuboki Y, Felip E, et al. Phase I dose escalation trial of the DLL3/CD3 Igg-Like T cell engager BI 764532 in patients with DLL3+ tumors: focus on SCLC. Presented at: 2023 World Conference on Lung Cancer; September 9-12, 2023. Abstract OA01.05
  20. Wermke M, Gambardella V, Kuboi Y, et al. Phase I trial of the delta-like ligand-3 (DLL3)/CD3 IgG-Like T cell engager BI 764532 in patients (pts) with DLL3-positive tumors: updated data. Ann Oncol. 2024;35:S482-S453.
  21. Beltran H, Johnson ML, Jain P, et al. Updated results from a phase 1/2 study of HPN328, a tri-specific, half-life (T1/2) extended DLL3-targeting T-cell engager in patients (pts) with small cell lung cancer (SCLC) and other neuroendocrine cancers (NEC). J Clin Oncol. 2024;42(16 suppl):8090.
  22. Dingemans AMC, Ahn MJ, Blackhall FH, et al. DeLLphi-301: tarlatamab phase 2 trial in small cell lung cancer (SCLC)—efficacy and safety analyzed by presence of brain metastasis. J Clin Oncol. 2024;42(16 suppl):8015.
  23. Choudhury NJ, Beltran H, Johnson ML, et al. Impact of brain metastases on safety and efficacy of MK-6070, a DLL3-targeting T cell engager, in small cell lung cancer. Presented at: 2024 World Conference on Lung Cancer; September 7-10, 2024. Abstract OA10.06.