Targeting CEACAM5 in NSCLC

CME

Research Focus: Targeting CEACAM5 With Novel Antibody‒Drug Conjugates in Nonsquamous Non-Small-Cell Lung Cancer

Physicians: Maximum of 0.50 AMA PRA Category 1 Credit

Released: June 09, 2023

Expiration: June 08, 2024

David Planchard
David Planchard, MD, PhD

Activity

Progress
1
Course Completed

References

  1. Thai AA, Solomon BJ, Sequist LV, et al. Lung Cancer. Lancet. 2021;398:535-554.
  2. Cheng Y, Zhang T, Xu Q. Therapeutic advances in non-small cell lung cancer: Focus on clinical development of targeted therapy and immunotherapy. MedComm (2020). 2021;2:692-729.
  3. Godoy LA, Chen J, Ma W, et al. Emerging precision neoadjuvant systemic therapy for patients with resectable non-small cell lung cancer: current status and perspectives. Biomark Res. 2023;11:7.
  4. Tsao AS, Scagliotti GV, Bunn PA Jr, et al. Scientific advances in lung cancer 2015. J Thorac Oncol. 2016;11:613-638.
  5. Burnett H, Emich H, Carroll C, et al. Epidemiological and clinical burden of EGFR exon 20 insertion in advanced non-small cell lung cancer: a systematic literature review. PLoS One. 2021;16:e0247620.
  6. Nassar AH, Adib E, Kwiatkowski DJ. Distribution of KRASG12C somatic mutations across race, sex, and cancer type. N Engl J Med. 2021;384:185-187.
  7. Jänne PA, Riely GJ, Gadgeel SM, et al. Adagrasib in non–small-cell lung cancer harboring a KRASG12C mutation. N Engl J Med. 2022;387:120-131.
  8. Ma Y, Pan H, Liu Y, et al. Ensartinib in advanced ALK-positive non-small cell lung cancer: a multicenter, open-label, two-staged, phase 1 trial. J Thorac Dis. 2022;14:4751-4762.
  9. Le X, Cornelissen R, Garassino M, et al. Poziotinib in non-small-cell lung cancer harboring HER2 exon 20 insertion mutations after prior therapies: ZENITH20-2 trial. J Clin Oncol. 2022;40:710-718.
  10. Li BT, Smit EF, Goto Y, et al. Trastuzumab deruxtecan in HER2-mutant non-small-cell lung cancer. N Engl J Med. 2022;386:241-251.
  11. Lau SCM, Batra U, Mok TSK, et al. Dacomitinib in the management of advanced non-small-cell lung cancer. Drugs. 2019;79:823-831.
  12. Olivier T, Prasad V. Amivantamab and mobocertinib in exon 20 insertions EGFR mutant lung cancer, challenge to the current guidelines. Transl Oncol. 2022;23:101475.
  13. Nakajima EC, Drezner N, Li X, et al. FDA approval summary: sotorasib for KRAS G12C-mutated metastatic NSCLC. Clin Cancer Res. 2022;28:1482-1486.
  14. Mathieu LN, Larkins E, Akinboro O, et al. FDA approval summary: capmatinib and tepotinib for the treatment of metastatic NSCLC harboring MET exon 14 skipping mutations or alterations. Clin Cancer Res. 2022;28:249-254.
  15. Zhao Y, Wang S, Yang Z, et al. Co-occurring potentially actionable oncogenic drivers in non-small cell lung cancer. Front Oncol. 2021;11:665484.
  16. National Comprehensive Cancer Network. Clinical practice guidelines in oncology: non-small cell lung cancer. v.3.2023. nccn.org. Accessed June 5, 2023.
  17. Pennell NA, Mutebi A, Zhou ZY, et al. Economic impact of next-generation sequencing versus single-gene testing to detect genomic alterations in metastatic non–small-cell lung cancer using a decision analytic model. JCO Precis Oncol. 2019;3:1-9.
  18. Murakami Y, Mitsudomi T, Yatabe Y. A screening method for the ALK fusion gene in NSCLC. Front Oncol. 2012;2:24.
  19. Esagian SM, Grigoriadou GI, Nikas IP, et al. Comparison of liquid-based to tissue-based biopsy analysis by targeted next generation sequencing in advanced non-small cell lung cancer: a comprehensive systematic review. J Cancer Res Clin Oncol. 2020;146:2051-2066.
  20. Benayed R, Offin M, Mullaney K, et al. High yield of RNA sequencing for targetable kinase fusions in lung adenocarcinomas with no mitogenic driver alteration detected by DNA sequencing and low tumor mutation burden. Clin Cancer Res. 2019;25:4712-4722.
  21. Cheng ML, Pectasides E, Hanna GJ, et al. Circulating tumor DNA in advanced solid tumors: clinical relevance and future directions. CA Cancer J Clin. 2021;71:176-190.
  22. Revelo AE, Martin A, Velasquez R, et al. Liquid biopsy for lung cancers: an update on recent developments. Ann Transl Med. 2019;7:349.
  23. Smith T, Knoll S, Martinalbo J, et al. Safety and efficacy of tusamitamab ravtansine in combination with pembrolizumab ± chemotherapy in patients with CEACAM5-positive nonsquamous NSCLC (CARMEN-LC05 phase 2 study). Presented at: 2021 World Conference on Lung Cancer; September 8-14, 2021. Abstract P10.07.
  24. Drago JZ, Modi S, Chandarlapaty S. Unlocking the potential of antibody-drug conjugates for cancer therapy. Nat Rev Clin Oncol. 2021;18:327-344.
  25. Mckertish CM, Kayser V. Advances and limitations of antibody drug conjugates for cancer. Biomedicines. 2021;9:872.
  26. Abuhelwa Z, Alloghbi A, Nagasaka M. A comprehensive review on antibody-drug conjugates (ADCs) in the treatment landscape of non-small cell lung cancer (NSCLC). Cancer Treat Rev. 2022;106:102393.
  27. Miranda O, Farooqui M, Siegfried JM. Status of agents targeting the HGF/c-Met axis in lung cancer. Cancers (Basel). 2018;10:280.
  28. Pouzin C, Gibiansky L, Fagniez N, et al. Integrated multiple analytes and semi-mechanistic population pharmacokinetic model of tusamitamab ravtansine, a DM4 anti-CEACAM5 antibody-drug conjugate. J Pharmacokinet Pharmacodyn. 2022;49:381-394.
  29. Nguyen TD, Bordeau BM, Balthasar JP. Mechanisms of ADC toxicity and strategies to increase ADC tolerability. Cancers (Basel). 2023;15:713.
  30. Johnson ML, Chadjaa M, Yoruk S, et al. Phase III trial comparing antibody-drug conjugate (ADC) SAR408701 with docetaxel in patients with metastatic non-squamous non-small cell lung cancer (NSQ NSCLC) failing chemotherapy and immunotherapy. Presented at: 2020 American Society of Clinical Oncology Virtual Scientific Program; May 29-31, 2020. Abstract TPS9625.
  31. Gazzah A, Ricordel C, Cousin S, et al. Efficacy and safety of the antibody-drug conjugate (ADC) SAR408701 in patients (pts) with non-squamous non-small cell lung cancer (NSQ NSCLC) expressing carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5). Presented at: 2020 American Society of Clinical Oncology Virtual Scientific Program; May 29-31, 2020. Abstract 9505.
  32. Beauchemin N, Arabzadeh A. Carcinoembryonic antigen-related cell adhesion molecules (CEACAMs) in cancer progression and metastasis. Cancer Metastasis Rev. 2013;32:643-671.
  33. Adam J, Lefebvre A, Nicolazzi C, et al. Therapeutic targets in non-small cell lung cancer: preclinical and human studies of carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) expression and its associated molecular landscape. Presented at: 2021 European Society for Medical Oncology Congress; September 16-21, 2021. Abstract 19P.
  34. Decary S, Berne P-F, Nicolazzi C, et al. Preclinical activity of SAR408701: a novel anti-CEACAM5-maytansinoid antibody-drug conjugate for the treatment of CEACAM5-positive epithelial tumors. Clin Cancer Res. 2020;26:6589-6599.
  35. Scoazec J, Bauchet A, Adam J, et al. Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) tumor expression in a phase I/II study of tusamitamab ravtansine (SAR408701) in patients (pts) with advanced non-small cell lung cancer (NSCLC). Presented at: 2021 European Society for Medical Oncology Congress; September 16-21, 2021. Abstract 1313P.
  36. Gazzah A, Bedard PL, Hierro C, et al. Safety, pharmacokinetics, and antitumor activity of the anti-CEACAM5-DM4 antibody-drug conjugate tusamitamab ravtansine (SAR408701) in patients with advanced solid tumors: first-in-human dose-escalation study. Ann Oncol. 2022;33:416-425.
  37. Vieito M, Tabernero J, Bedard P, et al. Dose escalation study of two different alternative dosing schedules of tusamitamab ravtansine (tusa, SAR408701) in patients (pts) with advanced solid tumors. Presented at: 2021 European Society for Medical Oncology Congress; September 16-21, 2021. Abstract 521P.
  38. Cho BC, Aguado de la Rosa C, Vilà L, et al. Phase II single-arm trial of safety, antitumor activity, and pharmacokinetics of tusamitamab ravtansine (SAR408701) plus ramucirumab in CEACAM5-positive, metastatic, non-squamous, non-small cell lung cancer progressing on platinum-based chemotherapy and immunotherapy. Presented at: 2021 European Society for Medical Oncology Congress; September 16-21, 2021. Abstract 1364TiP.
  39. Isambert N, Nagy T, Ravoire M, et al. Safety and efficacy of tusamitamab ravtansine in combination with pembrolizumab ± chemotherapy in patients with CEACAM5-positive nonsquamous NSCLC (CARMEN-LC05 phase 2 study). Presented at: 2023 European Lung Cancer Congress; March 29 - April 1, 2023. Abstract 13MO.
  40. Cousin S, Soufflet C. Tusamitamab ravtansine in patients with NSQ NSCLC and negative or moderate CEACAM5 expression tumors and high circulating CEA. Presented at: 2022 World Conference on Lung Cancer; August 6-9, 2022. Abstract EP08.02-030.
  41. Cole CB, Morelli MP, Fantini M, et al. Phase I clinical trial of NEO-201, an anti-tumor-associated CEACAM-5/6 monoclonal antibody in solid tumors. Presented at: 2022 American Society of Clinical Oncology Annual Meeting; June 3-7, 2022. Abstract 2531.
  42. Browning Cole C, Pia Morelli M, Fantini M, et al. Phase I clinical trial of NEO-201, an anti-tumor-associated CEACAM-5/6 monoclonal antibody in solid tumors. Presented at: 2022 American Society of Clinical Oncology Annual Meeting; June 3-7, 2022. Abstract 2531
  43. Robinson AA, Watson WJ, Leslie KK. Targeted treatment using monoclonal antibodies and tyrosine-kinase inhibitors in pregnancy. Lancet Oncol. 2007;8:738-743.
  44. 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.
  45. Lehtiö J, Arslan T, Siavelis I, et al. Proteogenomics of non-small cell lung cancer reveals molecular subtypes associated with specific therapeutic targets and immune evasion mechanisms. Nat Cancer. 2021;2:1224-1242.