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TROP2 TIGIT Lung Cancer

CE / CME

Expert Analysis: Clinical Advances Journal Club on Emerging TROP-2 and TIGIT Therapies in Lung Cancer

Physicians: Maximum of 1.00 AMA PRA Category 1 Credit

European Learners: 1.00 EBAC® CE Credit

Released: January 22, 2026

Expiration: July 21, 2026

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References

  1. Jiang A, Gao X, Zhang D, et al. Expression and clinical significance of the Trop-2 gene in advanced non-small cell lung carcinoma. Oncol Lett. 2013;6:375-380.
  2. Shvartsur A, Bonavida B. Trop2 and its overexpression in cancers: regulation and clinical/therapeutic implications. Genes Cancer. 2015;6:84-105.
  3. Okajima D, Yasuda S, Maejima T, et al. Datopotamab deruxtecan, a novel TROP2-directed antibody–drug conjugate, demonstrates potent antitumor activity by efficient drug delivery to tumor cells. Mol Cancer Ther. 2021;20:2329-2240.
  4. Kopp A, Hofsess S, Cardillo TM, et al. Antibody–drug conjugate sacituzumab govitecan drives efficient tissue penetration and rapid intracellular drug release. Mol Cancer Ther. 2023;22:102-111.
  5. Fang W, Wang Q, Cheng Y, et al. Sacituzumab tirumotecan (SKB264/MK-2870) in combination with KL-A167 (anti-PD-L1) as first-line treatment for patients with advanced NSCLC from the phase II OptiTROP-Lung01 study. Presented at: Annual Meeting of the American Society of Clinical Oncology; May 31-June 4, 2024. Abstract 8502.
  6. Ahn MJ, Tanaka K, Paz-Ares L, et al. Datopotamab deruxtecan versus docetaxel for previously treated advanced or metastatic non–small cell lung cancer: the randomized, open-label phase III TROPION-Lung01 study. J Clin Oncol. 2025;43:260-272.
  7. Paz-Ares LG, Juan-Vidal O, Mountzios GS, et al. Sacituzumab govitecan versus docetaxel for previously treated advanced or metastatic non–small cell lung cancer: the randomized, open-label phase III EVOKE-01 study. J Clin Oncol. 2024;42:2860-2872.
  8. Reinmuth N, Garassino MC, Juan-Vidal O, et al. Longer follow-up for survival and safety from the EVOKE-01 trial of sacituzumab govitecan (SG) vs docetaxel in patients (pts) with metastatic non-small cell lung cancer (mNSCLC). Presented at: Annual Meeting of the American Society of Clinical Oncology; May 30 - June 3, 2025. Abstract 8599.
  9. Ahn MJ, Sands J, Lisberg AE, et al. Efficacy and safety of datopotamab deruxtecan (Dato-DXd) in patients (pts) with previously-treated EGFR-mutated advanced non-small cell lung cancer (NSCLC): a pooled analysis of TROPION-Lung01 and TROPION-Lung05. Presented at: European Society for Medical Oncology Asia Congress; December 6-8, 2024. Abstract LBA7.
  10. Ahn MJ, Lisberg A, Goto Y, et al. A pooled analysis of datopotamab deruxtecan in patients with EGFR-mutated NSCLC. J Thorac Oncol. 2025;20:1669-1682.
  11. US Food and Drug Administration. FDA grants accelerated approval to datopotamab deruxtecan-dlnk for EGFR-mutated non-small cell lung cancer. fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-datopotamab-deruxtecan-dlnk-egfr-mutated-non-small-cell-lung-cancer. Accessed January 20, 2026.
  12. Sands J, Ahn MJ, Lisberg A, et al. Datopotamab deruxtecan in advanced or metastatic non–small cell lung cancer with actionable genomic alterations: results from the phase II TROPION-Lung05 study. J Clin Oncol. 2025;43:1254-1265.
  13. Levy BP, Paz-Ares LG, Lin CC, et al. TROPION-Lung02: datopotamab deruxtecan (Dato-DXd) plus pembrolizumab (pembro) with or without platinum chemotherapy (Pt-CT) as first-line (1L) therapy for advanced non-small cell lung cancer (aNSCLC). Presented at: Annual Meeting of the American Society of Clinical Oncology; May 30 - June 3, 2025. Abstract 8501.
  14. Gray J, Neal J, Patel JD, et al. Sacituzumab govitecan + pembrolizumab + carboplatin in 1L metastatic non-small cell lung cancer: the EVOKE-02 study. Presented at: 2024 World Conference on Lung Cancer; September 7-10, 2024. Abstract OA08.07.
  15. Reck M, Patel JD, Gray JE, et al. First-line sacituzumab govitecan plus pembrolizumab in metastatic NSCLC: PD-L1 TPS less than 50% and more than or equal to 50% cohorts of the EVOKE-02 study. J Thorac Oncol. 2025:S1556-0864(25)02890-4.
  16. Zhao S, Cheng Y, Wang Q, et al. Sacituzumab tirumotecan in advanced non-small-cell lung cancer with or without EGFR mutations: phase 1/2 and phase 2 trials. Nat Med. 2025;31:1976-1986.
  17. Gilead Sciences. U.S. FDA grants breakthrough therapy designation to Trodelvy® (sacituzumab govitecan-hziy) for second-line treatment of extensive-stage small cell lung cancer. gilead.com/news/news-details/2024/us-fda-grants-breakthrough-therapy-designation-to-trodelvy-sacituzumab-govitecan-hziy-for-second-line-treatment-of-extensive-stage-small-cell-lung-cancer. Accessed January 20, 2026.
  18. Zhang L, Fang W, Li X, et al. Sacituzumab tirumotecan (sac-TMT) in patients (pts) with previously treated advanced EGFR-mutated non-small cell lung cancer (NSCLC): results from the randomized OptiTROP-Lung03 study. Presented at: Annual Meeting of the American Society of Clinical Oncology; May 30 - June 3, 2025. Abstract 8507.
  19. Fang W, Li X, Wang Q, et al. Sacituzumab tirumotecan versus docetaxel for previously treated EGFR-mutated advanced non-small cell lung cancer: multicentre, open label, randomised controlled trial. BMJ. 2025;389:e085680.
  20. Zhang L, Fang WF, Wu L, et al. Sacituzumab tirumotecan (sac-TMT) vs platinum-based chemotherapy in EGFR-mutated (EGFRm) non-small cell lung cancer (NSCLC) following progression on EGFR-TKIs: results from the randomized, multi-center phase III OptiTROP-Lung04 study. Presented at: European Society for Medical Oncology Congress; October 17-21, 2025. Abstract LBA5.
  21. Fang W, Wu L, Meng X, et al. Sacituzumab tirumotecan in EGFR-TKI–resistant, EGFR-mutated advanced NSCLC. N Engl J Med. 2025;394:13-26.
  22. Planchard D, Jänne PA, Cheng Y, et al. Osimertinib with or without chemotherapy in EGFR-mutated advanced NSCLC. N Engl J Med. 2023;389:1935-1948.
  23. Datopotamab deruxtecan [prescribing information]. Basking Ridge, NJ: Daiichi Sankyo; 2025.
  24. National Comprehensive Cancer Network. Clinical practice guidelines in oncology: non-small cell lung cancer. v.3.2026. nccn.org. Accessed January 20, 2026.
  25. Chauvin JM, Zarour HM. TIGIT in cancer immunotherapy. J Immunother Cancer. 2020;8:e000957.
  26. Brandão M, Hiltermann JTJN, Wauters E, et al. Preliminary efficacy and safety of rilvegostomig (AZD2936), a bispecific antibody targeting PD-1 and TIGIT, in checkpoint inhibitor (CPI)-pretreated advanced/metastatic non-small-cell lung cancer (NSCLC): ARTEMIDE-01. Presented at: European Society for Medical Oncology Congress; October 20-24, 2023. Abstract 1446P.
  27. Guan X, Hu R, Choi Y, et al. Anti-TIGIT antibody improves PD-L1 blockade through myeloid and Treg cells. Nature. 2024;627:646-655.
  28. Rousseau A, Parisi C, Barlesi F. Anti-TIGIT therapies for solid tumors: a systematic review. ESMO Open. 2023;8:101184.
  29. Spigel DR, Korbenfeld EP, Hayashi H, et al. Interim analysis of GALAXIES Lung-201: phase II, randomized, open-label platform study of belrestotug plus dostarlimab in patients (pts) with previously untreated locally advanced/metastatic (LA/M) PD-L1 high (TPS >/=50%) non-small cell lung cancer (NSCLC). Presented at: European Society for Medical Oncology Congress; September 13-17, 2024. Abstract LBA52.
  30. GlobeNewswire. iTeos reports topline interim results from GALAXIES Lung-201 study of belrestotug + dostarlimab in first-line, PD-L1 high non-small cell lung cancer patients. globenewswire.com/news-release/2025/05/13/3080020/0/en/iTeos-Reports-Topline-Interim-Results-from-GALAXIES-Lung-201-Study-of-Belrestotug-Dostarlimab-in-First-Line-PD-L1-High-Non-Small-Cell-Lung-Cancer-Patients.html. Accessed January 20, 2026.
  31. Socinski MA, Rodriguez Abreu D, Lee DH, et al. SKYSCRAPER-06: Efficacy and safety of tiragolumab plus atezolizumab plus chemotherapy (tira + atezo + chemo) vs pembrolizumab plus chemotherapy (pembro + chemo) in patients (pts) with advanced non-squamous non-small cell lung cancer (NSq NSCLC). Presented at: ESMO Immuno-Oncology Congress 2024; December 11-13, 2024. Abstract LBA2.
  32. Peters S, Herbst R, Horinouchi H, et al. SKYSCRAPER-01: A phase III, randomized trial of tiragolumab (tira) + atezolizumab (atezo) versus placebo (pbo) + atezo in patients (pts) with previously-untreated PD-L1-high, locally advanced unresectable/metastatic NSCLC. Presented at: American Association for Cancer Research Annual Meeting 2025; April 25-30, 2025. Abstract CT051.
  33. Johnson ML, Fox W, Lee YG, et al. Randomized phase 2 study of domvanalimab + zimberelimab ± etrumadenant versus zimberelimab in first-line, metastatic, PD-L1-high non-small cell lung cancer (NSCLC). Presented at: Annual Meeting of the American Society of Clinical Oncology; June 2-6, 2023. Abstract 397600.
  34. Naidoo J, Peters S, Runglodvatana Y, et al. Phase 2 randomized study of domvanalimab combined with zimberelimab in front-line, PD-(L)1 high, locally advanced or metastatic non-small cell lung cancer (NSCLC): results from ARC-10 part 1. Presented at: 39th Annual Meeting of the Society for Immunotherapy of Cancer; November 6-10, 2024. Abstract 1461.
  35. Cho BC, Hiltermann JTJN, Izumi H, et al. Efficacy and safety of rilvegostomig, an anti-PD-1/TIGIT bispecific antibody, for checkpoint inhibitor (CPI)-naïve metastatic non-small cell lung cancer (mNSCLC): ARTEMIDE-01. Presented at: European Society for Medical Oncology Congress; October 17-21, 2025. Abstract 1853MO.
  36. Ahn MJ, Lee KH, Wang B, et al. Phase II study of sacituzumab govitecan (SG), domvanalimab (dom), and zimberelimab (zim) in metastatic non-small cell lung cancer (mNSCLC): VELOCITY-Lung substudy-01. Presented at: European Society for Medical Oncology Congress; October 17-21, 2025. Abstract 1947P.
  37. Dowlati A, Chiang AC, Cervantes A, et al. Sacituzumab govitecan as second-line treatment in patients with extensive stage small cell lung cancer. Presented at: 2024 World Conference on Lung Cancer; September 7-10, 2024. Abstract 0A4.04
  38. Dowlati A, Chiang AC, Cervantes A, et al. Phase 2 open-label study of sacituzumab govitecan as second-line therapy in patients with extensive-stage SCLC: results from TROPiCS-03. J Thorac Oncol. 2025;20:799-808.
  39. Rudin CM, Liu SV, Soo RA, et al. SKYSCRAPER-02: tiragolumab in combination with atezolizumab plus chemotherapy in untreated extensive-stage small-cell lung cancer. J Clin Oncol. 2024;42:324-335.
  40. Gong Y, Pang Q, Yu R, et al. AdvanTIG-204: a phase 2, multicenter, randomized, 3-arm, open-label study investigating the preliminary efficacy and safety of ociperlimab (anti-TIGIT) + tislelizumab (anti-PD-1) + concurrent chemoradiotherapy (cCRT) in patients with untreated limited-stage small cell lung cancer (SCLC). Presented at: American Association for Cancer Research Annual Meeting 2024; April 5-10, 2024. Abstract CT255.
  41. Gong Y, Pang Q, Yu R, et al. AdvanTIG-204: a phase 2, randomized, open-label study of ociperlimab plus tislelizumab and concurrent chemoradiotherapy versus tislelizumab and concurrent chemotherapy versus concurrent chemoradiotherapy in first-line limited-stage SCLC. JTO Clin Res Rep. 2025;6:100911.