Table Info

Table 1.

Key trials of ADCs in SCLC

Agent	Target	Trial identifier	Phase	ORR	OS	PFS	Grade 3 or > TRAEs
Rovalpituzumab tesirine	DLL3	NCT01901653	I	18%		2.8 mo (95% CI: 2.5–4.0)	38%
Rovalpituzumab tesirine	DLL3	TRINITY (NCT02674568)	II	12.4%	5.6 mo (95% CI: 4.9–6.1)	3.5 mo (95% CI: 3.0–3.9)	63%
Rovalpituzumab tesirine	DLL3	MERU (NCT03033511)	III		8.5 mo (95% CI: 7.3–10.2)	4.0 mo (95% CI: 3.2–4.1)	59%
Rovalpituzumab tesirine	DLL3	TAHOE (NCT03061812)	III		6.3 mo (95% CI: 5.6–7.3)	3.0 mo (95% CI: 2.9–3.6)	64%
Rovalpituzumab tesirine + ipilimumab & nivolumab	DLL3	NCT03026166	I/II	36.4% (95% CI: 10.9–69.2)	11.0 mo (95% CI: 2.3–17.0)	4.1 mo (95% CI: 1.3–6.0)	100%
Rovalpituzumab tesirine + nivolumab	DLL3	NCT03026166	I/II	27.6% (95% CI: 12.7–47.2)	7.4 mo (95% CI: 5.0–9.1)	4.8 mo (95% CI: 3.2–5.3)	87%
Sacituzumab govitecan	Trop2	IMMU-132-01 (NCT01631552)	I/II	17.70%	7.1 mo (95% CI: 5.6–8.1)	3.7 mo (95% CI: 2.1–4.8)	59.6%
Sacituzumab govitecan	Trop2	TROPiCS-03 (NCT03964727)	II	29% (95% CI: 8–58)			46%
Ifinatamab deruxtecan	B7-H3	NCT04145622	I/II	52%	9.9 mo	5.8 mo
HS-20093	B7-H3	ARTEMIS-001 (NCT05276609)	I	8 mg/kg dose: 58.1%		5.6 mo
ABBV-011	SEZ6	NCT03639194	I	25%		3.5 mo	47.5%
ABBV-706	SEZ6	NCT05599984	I	21%			57%
BL-B01D1	EGFR-HER3	NCT05194982	I	34%		5.7 mo	71%
Tusamitamab ravtansine	CEACAM5	NCT02187848	I				14.3% (Q2W-LD), 13.3% (Q3W)

ADCs: antibody drug conjugates; SCLC: small cell lung cancer; DLL3: delta-like ligand 3; Trop2: trophoblast cell surface antigen 2; SEZ6: seizure-related homolog 6; EGFR: epidermal growth factor receptor; CEACAM5: carcinoembryonic antigen-related cell adhesion molecule 5; CI: confidence interval; Q2W: every 2 weeks; ORR: objective response rate; OS: overall survival; PFS: progression-free survival; TRAEs: treatment-related adverse events; mo: month

Declarations

Author contributions

EIB, JC, and LF: Conceptualization, Data curation, Investigation, Project administration, Writing—original draft, Writing—review & editing. DP: Conceptualization, Investigation, Visualization, Project administration, Supervision, Writing—review & editing. SA: Conceptualization, Investigation, Project administration, Supervision, Writing—original draft, Writing—review & editing. RH: Conceptualization, Resources, Investigation, Project administration, Supervision, Writing—original draft, Writing—review & editing.

Conflicts of interest

RH is a consultant for Targeted Oncology, EMD Serono, and Takeda, received honoraria from DAVA Oncology, Targeted Oncology, and The Dedham Group, participated in an advisory board meeting for Oncohost, and receives institutional funding from Bristol Myers Squibb Foundation. All other authors declare no conflicts of interest.

Ethical approval

Not applicable.

Consent to participate

Not applicable.

Consent to publication

Not applicable.

Availability of data and materials

Not applicable.

Funding

Not applicable.

Copyright

Publisher’s note

Open Exploration maintains a neutral stance on jurisdictional claims in published institutional affiliations and maps. All opinions expressed in this article are the personal views of the author(s) and do not represent the stance of the editorial team or the publisher.

References

What Is Lung Cancer? [Internet]. American Cancer Society, Inc; c2025 [cited 2024 Aug 18]. Available from: https://www.cancer.org/cancer/lung-cancer/about/what-is.html

Byers LA, Rudin CM. Small cell lung cancer: where do we go from here? Cancer. 2015;121:664–72. [DOI] [PubMed] [PMC]

Gay CM, Stewart CA, Park EM, Diao L, Groves SM, Heeke S, et al. Patterns of transcription factor programs and immune pathway activation define four major subtypes of SCLC with distinct therapeutic vulnerabilities. Cancer Cell. 2021;39:346–60.e7. [DOI] [PubMed] [PMC]

Rudin CM, Poirier JT, Byers LA, Dive C, Dowlati A, George J, et al. Molecular subtypes of small cell lung cancer: a synthesis of human and mouse model data. Nat Rev Cancer. 2019;19:289–97. [DOI] [PubMed] [PMC]

Rudin CM, Ismaila N, Hann CL, Malhotra N, Movsas B, Norris K, et al. Treatment of Small-Cell Lung Cancer: American Society of Clinical Oncology Endorsement of the American College of Chest Physicians Guideline. J Clin Oncol. 2015;33:4106–11. [DOI]

Esposito G, Palumbo G, Carillio G, Manzo A, Montanino A, Sforza V, et al. Immunotherapy in Small Cell Lung Cancer. Cancers (Basel). 2020;12:2522. [DOI] [PubMed] [PMC]

Hodi FS, O’Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010;363:711–23. [DOI] [PubMed] [PMC]

Rizvi NA, Mazières J, Planchard D, Stinchcombe TE, Dy GK, Antonia SJ, et al. Activity and safety of nivolumab, an anti-PD-1 immune checkpoint inhibitor, for patients with advanced, refractory squamous non-small-cell lung cancer (CheckMate 063): A phase 2, single-arm trial. Lancet Oncol. 2015;16:257–65. [DOI]

Armstrong SA, Liu SV. Immune Checkpoint Inhibitors in Small Cell Lung Cancer: A Partially Realized Potential. Adv Ther. 2019;36:1826–32. [DOI] [PubMed] [PMC]

10.

Frampton JE. Atezolizumab: A Review in Extensive-Stage SCLC. Drugs. 2020;80:1587–94. [DOI] [PubMed]

11.

Liu SV, Reck M, Mansfield AS, Mok T, Scherpereel A, Reinmuth N, et al. Updated Overall Survival and PD-L1 Subgroup Analysis of Patients With Extensive-Stage Small-Cell Lung Cancer Treated With Atezolizumab, Carboplatin, and Etoposide (IMpower133). J Clin Oncol. 2021;39:619–30. [DOI] [PubMed] [PMC]

12.

Reck M, Dziadziuszko R, Sugawara S, Kao S, Hochmair M, Huemer F, et al. Five-year survival in patients with extensive-stage small cell lung cancer treated with atezolizumab in the Phase III IMpower133 study and the Phase III IMbrella A extension study. Lung Cancer. 2024;196:107924. [DOI] [PubMed]

13.

Paz-Ares L, Chen Y, Reinmuth N, Hotta K, Trukhin D, Statsenko G, et al. Durvalumab, with or without tremelimumab, plus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer: 3-year overall survival update from CASPIAN. ESMO Open. 2022;7:100408. [DOI] [PubMed] [PMC]

14.

Lim ZF, Ma PC. Emerging insights of tumor heterogeneity and drug resistance mechanisms in lung cancer targeted therapy. J Hematol Oncol. 2019;12:134. [DOI] [PubMed] [PMC]

15.

Stewart CA, Gay CM, Xi Y, Sivajothi S, Sivakamasundari V, Fujimoto J, et al. Single-cell analyses reveal increased intratumoral heterogeneity after the onset of therapy resistance in small-cell lung cancer. Nat Cancer. 2020;1:423–36. [DOI] [PubMed] [PMC]

16.

Spigel DR, Vicente D, Ciuleanu TE, Gettinger S, Peters S, Horn L, et al. Second-line nivolumab in relapsed small-cell lung cancer: CheckMate 331^☆. Ann Oncol. 2021;32:631–41. [DOI] [PubMed]

17.

Cohen RB, Delord JP, Doi T, Piha-Paul SA, Liu SV, Gilbert J, et al. Pembrolizumab for the Treatment of Advanced Salivary Gland Carcinoma: Findings of the Phase 1b KEYNOTE-028 Study. Am J Clin Oncol. 2018;41:1083–8. [DOI] [PubMed] [PMC]

18.

Marabelle A, Le DT, Ascierto PA, Di Giacomo AM, De Jesus-Acosta A, Delord JP, et al. Efficacy of Pembrolizumab in Patients With Noncolorectal High Microsatellite Instability/Mismatch Repair-Deficient Cancer: Results From the Phase II KEYNOTE-158 Study. J Clin Oncol. 2020;38:1–10. [DOI] [PubMed] [PMC]

19.

Das M, Padda SK, Weiss J, Owonikoko TK. Advances in Treatment of Recurrent Small Cell Lung Cancer (SCLC): Insights for Optimizing Patient Outcomes from an Expert Roundtable Discussion. Adv Ther. 2021;38:5431–51. [DOI] [PubMed] [PMC]

20.

Mondelo-Macía P, García-González J, León-Mateos L, Castillo-García A, López-López R, Muinelo-Romay L, et al. Current Status and Future Perspectives of Liquid Biopsy in Small Cell Lung Cancer. Biomedicines. 2021;9:48. [DOI] [PubMed] [PMC]

21.

Adhit KK, Wanjari A, Menon S, K S. Liquid Biopsy: An Evolving Paradigm for Non-invasive Disease Diagnosis and Monitoring in Medicine. Cureus. 2023;15:e50176. [DOI] [PubMed] [PMC]

22.

Grenda A, Krawczyk P, Obara A, Gajek Ł, Łomża-Łaba A, Milanowski J. Transitioning to a Personalized Approach in Molecularly Subtyped Small-Cell Lung Cancer (SCLC). Int J Mol Sci. 2024;25:4208. [DOI] [PubMed] [PMC]

23.

Wang Q, Gümüş ZH, Colarossi C, Memeo L, Wang X, Kong CY, et al. SCLC: Epidemiology, Risk Factors, Genetic Susceptibility, Molecular Pathology, Screening, and Early Detection. J Thorac Oncol. 2023;18:31–46. [DOI] [PubMed] [PMC]

24.

George J, Lim JS, Jang SJ, Cun Y, Ozretić L, Kong G, et al. Comprehensive genomic profiles of small cell lung cancer. Nature. 2015;524:47–53. [DOI] [PubMed] [PMC]

25.

Rudin CM, Brambilla E, Faivre-Finn C, Sage J. Small-cell lung cancer. Nat Rev Dis Primers. 2021;7:3. [DOI] [PubMed] [PMC]

26.

Peifer M, Fernández-Cuesta L, Sos ML, George J, Seidel D, Kasper LH, et al. Integrative genome analyses identify key somatic driver mutations of small-cell lung cancer. Nat Genet. 2012;44:1104–10. [DOI] [PubMed] [PMC]

27.

Mollaoglu G, Guthrie MR, Böhm S, Brägelmann J, Can I, Ballieu PM, et al. MYC Drives Progression of Small Cell Lung Cancer to a Variant Neuroendocrine Subtype with Vulnerability to Aurora Kinase Inhibition. Cancer Cell. 2017;31:270–85. [DOI] [PubMed] [PMC]

28.

Horn L, Mansfield AS, Szczęsna A, Havel L, Krzakowski M, Hochmair MJ, et al.; IMpower133 Study Group. First-Line Atezolizumab plus Chemotherapy in Extensive-Stage Small-Cell Lung Cancer. N Engl J Med. 2018;379:2220–9. [DOI] [PubMed]

29.

Hurwitz J, Haggstrom LR, Lim E. Antibody-Drug Conjugates: Ushering in a New Era of Cancer Therapy. Pharmaceutics. 2023;15:2017. [DOI] [PubMed] [PMC]

30.

Fu Z, Li S, Han S, Shi C, Zhang Y. Antibody drug conjugate: the “biological missile” for targeted cancer therapy. Signal Transduct Target Ther. 2022;7:93. [DOI] [PubMed] [PMC]

31.

Coleman N, Yap TA, Heymach JV, Meric-Bernstam F, Le X. Antibody-drug conjugates in lung cancer: dawn of a new era? NPJ Precis Oncol. 2023;7:5. [DOI] [PubMed] [PMC]

32.

Smits NC, Sentman CL. Bispecific T-Cell Engagers (BiTEs) as Treatment of B-Cell Lymphoma. J Clin Oncol. 2016;34:1131–3. [DOI] [PubMed] [PMC]

33.

Staerz UD, Kanagawa O, Bevan MJ. Hybrid antibodies can target sites for attack by T cells. Nature (London). 1985;314:628–31. [DOI]

34.

Mitra A, Barua A, Huang L, Ganguly S, Feng Q, He B. From bench to bedside: the history and progress of CAR T cell therapy. Front Immunol. 2023;14:1188049. [DOI] [PubMed] [PMC]

35.

Hwu P, Shafer GE, Treisman J, Schindler DG, Gross G, Cowherd R, et al. Lysis of ovarian cancer cells by human lymphocytes redirected with a chimeric gene composed of an antibody variable region and the Fc receptor gamma chain. J Exp Med. 1993;178:361–6. [DOI] [PubMed] [PMC]

36.

Maude SL, Laetsch TW, Buechner J, Rives S, Boyer M, Bittencourt H, et al. Tisagenlecleucel in Children and Young Adults with B-Cell Lymphoblastic Leukemia. N Engl J Med. 2018;378:439–48. [DOI] [PubMed] [PMC]

37.

Feins S, Kong W, Williams EF, Milone MC, Fraietta JA. An introduction to chimeric antigen receptor (CAR) T-cell immunotherapy for human cancer. Am J Hematol. 2019;94:S3–9. [DOI] [PubMed]

38.

biorender.com [Internet]. BioRender; c2025 [cited 2025 Jan 29]. Available from: https://www.biorender.com/

39.

Beck A, Goetsch L, Dumontet C, Corvaïa N. Strategies and challenges for the next generation of antibody-drug conjugates. Nat Rev Drug Discov. 2017;16:315–37. [DOI] [PubMed]

40.

Chau CH, Steeg PS, Figg WD. Antibody-drug conjugates for cancer. Lancet. 2019;394:793–804. [DOI] [PubMed]

41.

Rudin CM, Pietanza MC, Bauer TM, Ready N, Morgensztern D, Glisson BS, et al.; SCRX16-001 investigators. Rovalpituzumab tesirine, a DLL3-targeted antibody-drug conjugate, in recurrent small-cell lung cancer: a first-in-human, first-in-class, open-label, phase 1 study. Lancet Oncol. 2017;18:42–51. [DOI] [PubMed] [PMC]

42.

Rojo F, Corassa M, Mavroudis D, Öz AB, Biesma B, Brcic L, et al. International real-world study of DLL3 expression in patients with small cell lung cancer. Lung Cancer. 2020;147:237–43. [DOI] [PubMed]

43.

Morgensztern D, Besse B, Greillier L, Santana-Davila R, Ready N, Hann CL, et al. Efficacy and Safety of Rovalpituzumab Tesirine in Third-Line and Beyond Patients with DLL3-Expressing, Relapsed/Refractory Small-Cell Lung Cancer: Results From the Phase II TRINITY Study. Clin Cancer Res. 2019;25:6958–66. [DOI] [PubMed] [PMC]

44.

Johnson ML, Zvirbule Z, Laktionov K, Helland A, Cho BC, Gutierrez V, et al. Rovalpituzumab Tesirine as a Maintenance Therapy After First-Line Platinum-Based Chemotherapy in Patients With Extensive-Stage–SCLC: Results From the Phase 3 MERU Study. J Thor Oncol. 2021;16:1570–81. [DOI] [PubMed]

45.

Blackhall F, Jao K, Greillier L, Cho BC, Penkov K, Reguart N, et al. Efficacy and Safety of Rovalpituzumab Tesirine Compared With Topotecan as Second-Line Therapy in DLL3-High SCLC: Results From the Phase 3 TAHOE Study. J Thorac Oncol. 2021;16:1547–58. [DOI] [PubMed]

46.

Malhotra J, Nikolinakos P, Leal T, Lehman J, Morgensztern D, Patel JD, et al. A Phase 1-2 Study of Rovalpituzumab Tesirine in Combination With Nivolumab Plus or Minus Ipilimumab in Patients With Previously Treated Extensive-Stage SCLC. J Thorac Oncol. 2021;16:1559–69. [DOI] [PubMed]

47.

Guo Q, Gao B, Song R, Li W, Zhu S, Xie Q, et al. FZ-AD005, a Novel DLL3-Targeted Antibody–Drug Conjugate with Topoisomerase I Inhibitor, Shows Potent Antitumor Activity in Preclinical Models. Mol Cancer Ther. 2024;23:1367–77. [DOI] [PubMed] [PMC]

48.

Shvartsur A, Bonavida B. Trop2 and its overexpression in cancers: regulation and clinical/therapeutic implications. Genes Cancer. 2015;6:84–105. [DOI] [PubMed] [PMC]

49.

Cardillo TM, Govindan SV, Sharkey RM, Trisal P, Goldenberg DM. Humanized anti-Trop-2 IgG-SN-38 conjugate for effective treatment of diverse epithelial cancers: preclinical studies in human cancer xenograft models and monkeys. Clin Cancer Res. 2011;17:3157–69. [DOI] [PubMed] [PMC]

50.

Bardia A, Mayer IA, Diamond JR, Moroose RL, Isakoff SJ, Starodub AN, et al. Efficacy and Safety of Anti-Trop-2 Antibody Drug Conjugate Sacituzumab Govitecan (IMMU-132) in Heavily Pretreated Patients With Metastatic Triple-Negative Breast Cancer. J Clin Oncol. 2017;35:2141–8. [DOI] [PubMed] [PMC]

51.

Starodub AN, Ocean AJ, Shah MA, Guarino MJ, Picozzi VJ Jr, Vahdat LT, et al. First-in-human trial of a novel anti-trop-2 Antibody-SN-38 conjugate, sacituzumab govitecan, for the treatment of diverse metastatic solid tumors. Clin Cancer Res. 2015;21:3870–8. [DOI] [PubMed] [PMC]

52.

Bardia A, Messersmith WA, Kio EA, Berlin JD, Vahdat L, Masters GA, et al. Sacituzumab govitecan, a Trop-2-directed antibody-drug conjugate, for patients with epithelial cancer: final safety and efficacy results from the phase I/II IMMU-132-01 basket trial. Ann Oncol. 2021;32:746–56. [DOI] [PubMed]

53.

Dowlati A, Cervantes A, Babu S, Hamilton EP, Wong SF, Tazbirkova A, et al. 1990MO Sacituzumab govitecan (SG) as second-line (2L) treatment for extensive stage small cell lung cancer (ES-SCLC): Preliminary results from the phase II TROPiCS-03 basket trial. Ann Oncol. 2023;34:S1060–1. [DOI]

54.

Abel ML, Takahashi N, Peer C, Redon CE, Nichols S, Vilimas R, et al. Targeting Replication Stress and Chemotherapy Resistance with a Combination of Sacituzumab Govitecan and Berzosertib: A Phase I Clinical Trial. Clin Cancer Res. 2023;29:3603–11. [DOI] [PubMed] [PMC]

55.

Cheng Y, Yuan X, Tian Q, Huang X, Chen Y, Pu Y, et al. Preclinical profiles of SKB264, a novel anti-TROP2 antibody conjugated to topoisomerase inhibitor, demonstrated promising antitumor efficacy compared to IMMU-132. Front Oncol. 2022;12:951589. [DOI] [PubMed] [PMC]

56.

Rodon J, Wainberg ZA, Zhang M, Liu T, Liu B, Yu G, et al. Abstract CT038: Preliminary efficacy and safety results of anti-TROP2 ADC SKB264 (MK-2870) in patients (pts) with previously treated advanced gastric (G) or gastroesophageal junction (GEJ) cancer from a Phase 2 study. Cancer Res. 2024;84:CT038. [DOI]

57.

Fang W, Cheng Y, Chen Z, Wang W, Li Y, Yin Y, et al. Abstract CT247: Updated efficacy and safety of anti-TROP2 ADC SKB264 (MK-2870) for previously treated advanced NSCLC in Phase 2 study. Cancer Res. 2024;84:CT247. [DOI]

58.

Yin Y, Wu X, Ouyang Q, Yan M, Song L, Liu Y, et al. Abstract PS08-08: Updated efficacy and safety of SKB264 (MK-2870) for previously treated metastatic triple negative breast cancer (mTNBC) in Phase 2 study. Cancer Res. 2024;84:PS08-08. [DOI]

59.

Shimizu T, Sands J, Yoh K, Spira A, Garon EB, Kitazono S, et al. First-in-Human, Phase I Dose-Escalation and Dose-Expansion Study of Trophoblast Cell-Surface Antigen 2-Directed Antibody-Drug Conjugate Datopotamab Deruxtecan in Non-Small-Cell Lung Cancer: TROPION-PanTumor01. J Clin Oncol. 2023;41:4678–87. [DOI] [PubMed] [PMC]

60.

Kontos F, Michelakos T, Kurokawa T, Sadagopan A, Schwab JH, Ferrone CR, et al. B7-H3: An Attractive Target for Antibody-based Immunotherapy. Clin Cancer Res. 2021;27:1227–35. [DOI] [PubMed] [PMC]

61.

Carvajal-Hausdorf D, Altan M, Velcheti V, Gettinger SN, Herbst RS, Rimm DL, et al. Expression and clinical significance of PD-L1, B7-H3, B7-H4 and TILs in human small cell lung Cancer (SCLC). J Immunother Cancer. 2019;7:65. [DOI] [PubMed] [PMC]

62.

Patel MR, Doi T, Koyama T, Falchook GS, Friedman CF, Piha-Paul SA, et al. 690P Ifinatamab deruxtecan (I-DXd; DS-7300) in patients with advanced solid tumors: Updated clinical and biomarker results from a phase I/II study. Ann Oncol. 2023;34:S481–2. [DOI]

63.

Feustel K, Martin J, Falchook GS. B7-H3 Inhibitors in Oncology Clinical Trials: A Review. J Immunother Precis Oncol. 2024;7:53–66. [DOI] [PubMed] [PMC]

64.

Wang J, Duan J, Sun Y, Xing L, Han L, Wang Q, et al. ARTEMIS-001: Data from a phase 1a/b study of HS-20093 in patients with relapsed small cell lung cancer (SCLC). J Clin Oncol. 2024;42:8093. [DOI]

65.

Wiedemeyer WR, Gavrilyuk J, Schammel A, Zhao X, Sarvaiya H, Pysz M, et al. ABBV-011, A Novel, Calicheamicin-Based Antibody–Drug Conjugate, Targets SEZ6 to Eradicate Small Cell Lung Cancer Tumors. Mol Cancer Ther. 2022;21:986–98. [DOI] [PubMed] [PMC]

66.

Morgensztern D, Ready NE, Johnson ML, Dowlati A, Choudhury NJ, DP Carbone, et al. First-in-human study of ABBV-011, a seizure-related homolog protein 6 (SEZ6)–targeting antibody-drug conjugate, in patients with small cell lung cancer. J Clin Oncol. 2023;41:3002. [DOI]

67.

Chandana SR, Choudhury NJ, Dowlati A, Chiang AC, Garmezy B, Kim JH, et al. First-in-human study of ABBV-706, a seizure-related homolog protein 6 (SEZ6)-targeting antibody-drug conjugate (ADC), in patients (pts) with advanced solid tumors. J Clin Oncol. 2024;42:3001. [DOI]

68.

Workman P, Powers MV. Chaperoning cell death: a critical dual role for Hsp90 in small-cell lung cancer. Nat Chem Biol. 2007;3:455–7. [DOI] [PubMed]

69.

Gaponova AV, Nikonova AS, Deneka AY, Kopp MC, Kudinov AE, Skobeleva N, et al. A novel HSP90 inhibitor-drug conjugate to SN38 is highly effective in small cell lung cancer. Clin Cancer Res. 2016;22:5120–9. [DOI]

70.

Falchook GS, Bendell JC, Ulahannan SV, Sen S, Vilimas R, Kriksciukaite K, et al. Pen-866, a miniature drug conjugate of a heat shock protein 90 (HSP90) ligand linked to SN38 for patients with advanced solid malignancies: Phase I and expansion cohort results. J Clin Oncol. 2020;38:3515. [DOI]

71.

Micke P, Hengstler JG, Ros R, Bittinger F, Metz T, Gebhard S, et al. c-erbB-2 expression in small-cell lung cancer is associated with poor prognosis. Int J Cancer. 2001;92:474–9. [DOI] [PubMed]

72.

Ma Y, Huang Y, Zhao Y, Zhao S, Xue J, Yang 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;25:901–11. [DOI] [PubMed]

73.

Wan W, Zhao S, Zhuo S, Zhang Y, Chen L, Li G, et al. Abstract 2642: BL-B01D1, a novel EGFR×HER3-targeting ADC, demonstrates robust anti-tumor efficacy in preclinical evaluation. Cancer Res. 2023;83:2642. [DOI]

74.

Blumenthal RD, Hansen HJ, Goldenberg DM. Inhibition of adhesion, invasion, and metastasis by antibodies targeting CEACAM6 (NCA-90) and CEACAM5 (Carcinoembryonic Antigen). Cancer Res. 2005;65:8809–17. [DOI] [PubMed]

75.

Tabernero J, Bedard PL, Bang YJ, Vieito M, Ryu MH, Fagniez N, et al. Tusamitamab Ravtansine in Patients with Advanced Solid Tumors: Phase I Study of Safety, Pharmacokinetics, and Antitumor Activity Using Alternative Dosing Regimens. Cancer Res Commun. 2023;3:1662–71. [DOI] [PubMed] [PMC]

76.

Zhou S, Liu M, Ren F, Meng X, Yu J. The landscape of bispecific T cell engager in cancer treatment. Biomark Res. 2021;9:38. [DOI] [PubMed] [PMC]

77.

Baeuerle PA, Reinhardt C. Bispecific T-cell engaging antibodies for cancer therapy. Cancer Res. 2009;69:4941–4. [DOI] [PubMed]

78.

Borlak J, Länger F, Spanel R, Schöndorfer G, Dittrich C. Immune-mediated liver injury of the cancer therapeutic antibody catumaxomab targeting EpCAM, CD3 and Fcγ receptors. Oncotarget. 2016;7:28059–74. [DOI] [PubMed] [PMC]

79.

Fucà G, Spagnoletti A, Ambrosini M, de Braud F, Di Nicola M. Immune cell engagers in solid tumors: promises and challenges of the next generation immunotherapy. ESMO Open. 2021;6:100046. [DOI] [PubMed] [PMC]

80.

Pishvaian M, Morse MA, McDevitt J, Norton JD, Ren S, Robbie GJ, et al. Phase 1 Dose Escalation Study of MEDI-565, a Bispecific T-Cell Engager that Targets Human Carcinoembryonic Antigen, in Patients With Advanced Gastrointestinal Adenocarcinomas. Clin Colorectal Cancer. 2016;15:345–51. [DOI] [PubMed]

81.

Giffin M, Cooke K, Lobenhofer E, Friedrich M, Raum T, Coxon A. P3.12-03 Targeting DLL3 with AMG 757, a BiTE® Antibody Construct, and AMG 119, a CAR-T, for the Treatment of SCLC. J Thor Oncol. 2018;13:S971. [DOI]

82.

Paz-Ares L, Champiat S, Lai WV, Izumi H, Govindan R, Boyer M, et al. Tarlatamab, a First-in-Class DLL3-Targeted Bispecific T-Cell Engager, in Recurrent Small-Cell Lung Cancer: An Open-Label, Phase I Study. J Clin Oncol. 2023;41:2893–903. [DOI] [PubMed] [PMC]

83.

Ahn MJ, Cho BC, Felip E, Korantzis I, Ohashi K, Majem M, et al.; DeLLphi-301 Investigators. Tarlatamab for Patients with Previously Treated Small-Cell Lung Cancer. N Engl J Med. 2023;389:2063–75. [DOI] [PubMed]

84.

Sadelain M, Brentjens R, Rivière I. The promise and potential pitfalls of chimeric antigen receptors. Curr Opin Immunol. 2009;21:215–23. [DOI] [PubMed] [PMC]

85.

Newick K, O’Brien S, Moon E, Albelda SM. CAR T Cell Therapy for Solid Tumors. Annu Rev Med. 2017;68:139–52. [DOI] [PubMed]

86.

June CH, Sadelain M. Chimeric Antigen Receptor Therapy. N Engl J Med. 2018;379:64–73. [DOI] [PubMed] [PMC]

87.

Maude SL, Frey N, Shaw PA, Aplenc R, Barrett DM, Bunin NJ, et al. Chimeric antigen receptor T cells for sustained remissions in leukemia. N Engl J Med. 2014;371:1507–17. [DOI] [PubMed] [PMC]

88.

Drougkas K, Karampinos K, Karavolias I, Koumprentziotis IA, Ploumaki I, Triantafyllou E, et al. Comprehensive clinical evaluation of CAR-T cell immunotherapy for solid tumors: a path moving forward or a dead end? J Cancer Res Clin Oncol. 2023;149:2709–34. [DOI] [PubMed] [PMC]

89.

Martinez M, Moon EK. CAR T Cells for Solid Tumors: New Strategies for Finding, Infiltrating, and Surviving in the Tumor Microenvironment. Front Immunol. 2019;10:128. [DOI] [PubMed] [PMC]

90.

White LG, Goy HE, Rose AJ, McLellan AD. Controlling Cell Trafficking: Addressing Failures in CAR T and NK Cell Therapy of Solid Tumours. Cancers (Basel). 2022;14:978. [DOI] [PubMed] [PMC]

91.

Haas AR, Tanyi JL, O’Hara MH, Gladney WL, Lacey SF, Torigian DA, et al. Phase I Study of Lentiviral-Transduced Chimeric Antigen Receptor-Modified T Cells Recognizing Mesothelin in Advanced Solid Cancers. Mol Ther. 2019;27:1919–29. [DOI] [PubMed] [PMC]

92.

Bräunlein E, Krackhardt AM. Identification and Characterization of Neoantigens As Well As Respective Immune Responses in Cancer Patients. Front Immunol. 2017;8:1702. [DOI] [PubMed] [PMC]

93.

Sharma SK, Pourat J, Abdel-Atti D, Carlin SD, Piersigilli A, Bankovich AJ, et al. Noninvasive Interrogation of DLL3 Expression in Metastatic Small Cell Lung Cancer. Cancer Res. 2017;77:3931–41. [DOI] [PubMed] [PMC]

94.

Byers L, Heymach J, Gibbons D, Zhang J, Chiappori A, Rasmussen E, et al. 697 A phase 1 study of AMG 119, a DLL3-targeting, chimeric antigen receptor (CAR) T cell therapy, in relapsed/refractory small cell lung cancer (SCLC). J Immunother Cancer. 2022;10. [DOI]

95.

Zhang Y, Tacheva-Grigorova SK, Sutton J, Melton Z, Mak YSL, Lay C, et al. Allogeneic CAR T Cells Targeting DLL3 Are Efficacious and Safe in Preclinical Models of Small Cell Lung Cancer. Clin Cancer Res. 2023;29:971–85. [DOI] [PubMed]

96.

Jaspers JE, Khan JF, Godfrey WD, Lopez AV, Ciampricotti M, Rudin CM, et al. IL-18-secreting CAR T cells targeting DLL3 are highly effective in small cell lung cancer models. J Clin Invest. 2023;133:e166028. [DOI] [PubMed] [PMC]

97.

Nie F, Chen Y, Hu Y, Huang P, Shi X, Cai J, et al. TREM1/DAP12 based novel multiple chain CAR-T cells targeting DLL3 show robust anti-tumour efficacy for small cell lung cancer. Immunology. 2024;172:362–74. [DOI] [PubMed]

98.

Liu M, Huang W, Guo Y, Zhou Y, Zhi C, Chen J, et al. CAR NK-92 cells targeting DLL3 kill effectively small cell lung cancer cells in vitro and in vivo. J Leukoc Biol. 2022;112:901–11. [DOI] [PubMed]

99.

Montagner IM, Penna A, Fracasso G, Carpanese D, Dalla Pietà A, Barbieri V, et al. Anti-PSMA CAR-engineered NK-92 Cells: An Off-the-shelf Cell Therapy for Prostate Cancer. Cells. 2020;9:1382. [DOI] [PubMed] [PMC]

100.

Kieliszek AM, Mobilio D, Upreti D, Bloemberg D, Escudero L, Kwiecien JM, et al. Intratumoral Delivery of Chimeric Antigen Receptor T Cells Targeting CD133 Effectively Treats Brain Metastases. Clin Cancer Res. 2024;30:554–63. [DOI] [PubMed]

101.

Taromi S, Firat E, Simonis A, Braun LM, Apostolova P, Elze M, et al. Enhanced AC133-specific CAR T cell therapy induces durable remissions in mice with metastatic small cell lung cancer. Cancer Lett. 2022;538:215697. [DOI] [PubMed]

102.

Krengel U, Bousquet PA. Molecular recognition of gangliosides and their potential for cancer immunotherapies. Front Immunol. 2014;5:325. [DOI] [PubMed] [PMC]

103.

Del Bufalo F, De Angelis B, Caruana I, Del Baldo G, De Ioris MA, Serra A, et al.; Precision Medicine Team–IRCCS Ospedale Pediatrico Bambino Gesù. GD2-CART01 for Relapsed or Refractory High-Risk Neuroblastoma. N Engl J Med. 2023;388:1284–95. [DOI] [PubMed]

104.

Yoshida S, Fukumoto S, Kawaguchi H, Sato S, Ueda R, Furukawa K. Ganglioside G(D2) in small cell lung cancer cell lines: enhancement of cell proliferation and mediation of apoptosis. Cancer Res. 2001;61:4244–52. [PubMed]

105.

Cheresh DA, Rosenberg J, Mujoo K, Hirschowitz L, Reisfeld RA. Biosynthesis and expression of the disialoganglioside GD2, a relevant target antigen on small cell lung carcinoma for monoclonal antibody-mediated cytolysis. Cancer Res. 1986;46:5112–8. [PubMed]

106.

Reppel L, Tsahouridis O, Akulian J, Davis IJ, Lee H, Fucà G, et al. Targeting disialoganglioside GD2 with chimeric antigen receptor-redirected T cells in lung cancer. J Immunother Cancer. 2022;10:e003897. [DOI] [PubMed] [PMC]

107.

Kinoshita S, Ishii M, Ando J, Kimura T, Yamaguchi T, Harada S, et al. Rejuvenated iPSC-derived GD2-directed CART Cells Harbor Robust Cytotoxicity Against Small Cell Lung Cancer. Cancer Res Commun. 2024;4:723–37. [DOI] [PubMed] [PMC]

108.

Sasaki T, Sakoda Y, Adachi K, Tokunaga Y, Tamada K. Therapeutic effects of anti-GM2 CAR-T cells expressing IL-7 and CCL19 for GM2-positive solid cancer in xenograft model. Cancer Med. 2023;12:12569–80. [DOI] [PubMed] [PMC]

109.

Teicher BA. Targets in small cell lung cancer. Biochem Pharmacol. 2014;87:211–9. [DOI] [PubMed]

110.

Socinski MA, Kaye FJ, Spigel DR, Kudrik FJ, Ponce S, Ellis PM, et al. Phase 1/2 Study of the CD56-Targeting Antibody-Drug Conjugate Lorvotuzumab Mertansine (IMGN901) in Combination With Carboplatin/Etoposide in Small-Cell Lung Cancer Patients With Extensive-Stage Disease. Clin Lung Cancer. 2017;18:68–76.e2. [DOI] [PubMed]

111.

Crossland DL, Denning WL, Ang S, Olivares S, Mi T, Switzer K, et al. Antitumor activity of CD56-chimeric antigen receptor T cells in neuroblastoma and SCLC models. Oncogene. 2018;37:3686–97. [DOI] [PubMed]

112.

Denninghoff V, Russo A, de Miguel-Pérez D, Malapelle U, Benyounes A, Gittens A, et al. Small Cell Lung Cancer: State of the Art of the Molecular and Genetic Landscape and Novel Perspective. Cancers (Basel). 2021;13:1723. [DOI] [PubMed] [PMC]

113.

Cardillo TM, Rossi DL, Zalath MB, Liu D, Arrojo R, Sharkey RM, et al. Predictive biomarkers for sacituzumab govitecan efficacy in Trop-2-expressing triple-negative breast cancer. Oncotarget. 2020;11:3849–62. [DOI] [PubMed] [PMC]

114.

Zhu Y, Liu K, Wang K, Zhu H. Treatment-related adverse events of antibody-drug conjugates in clinical trials: A systematic review and meta-analysis. Cancer. 2023;129:283–95. [DOI] [PubMed] [PMC]

115.

Li BT, Smit EF, Goto Y, Nakagawa K, Udagawa H, Mazières J, et al.; DESTINY-Lung01 Trial Investigators. Trastuzumab Deruxtecan in HER2-Mutant Non-Small-Cell Lung Cancer. N Engl J Med. 2022;386:241–51. [DOI] [PubMed] [PMC]

116.

Ganatra S, Dani SS, Yang EH, Zaha VG, Nohria A. Cardiotoxicity of T-Cell Antineoplastic Therapies: JACC: CardioOncology Primer. JACC CardioOncol. 2022;4:616–23. [DOI] [PubMed] [PMC]

117.

Hamilton G, Rath B. Immunotherapy for small cell lung cancer: mechanisms of resistance. Expert Opin Biol Ther. 2019;19:423–32. [DOI] [PubMed]

118.

Passaro A, Brahmer J, Antonia S, Mok T, Peters S. Managing Resistance to Immune Checkpoint Inhibitors in Lung Cancer: Treatment and Novel Strategies. J Clin Oncol. 2022;40:598–610. [DOI] [PubMed]

119.

Abelman RO, Wu B, Spring LM, Ellisen LW, Bardia A. Mechanisms of Resistance to Antibody-Drug Conjugates. Cancers (Basel). 2023;15:1278. [DOI] [PubMed] [PMC]

120.

Braig F, Brandt A, Goebeler M, Tony HP, Kurze AK, Nollau P, et al. Resistance to anti-CD19/CD3 BiTE in acute lymphoblastic leukemia may be mediated by disrupted CD19 membrane trafficking. Blood. 2017;129:100–4. [DOI] [PubMed]

121.

Middelburg J, Kemper K, Engelberts P, Labrijn AF, Schuurman J, van Hall T. Overcoming Challenges for CD3-Bispecific Antibody Therapy in Solid Tumors. Cancers (Basel). 2021;13:287. [DOI] [PubMed] [PMC]

122.

Shah NN, Fry TJ. Mechanisms of resistance to CAR T cell therapy. Nat Rev Clin Oncol. 2019;16:372–85. [DOI] [PubMed] [PMC]

123.

Zhu WM, Middleton MR. Combination therapies for the optimisation of Bispecific T-cell Engagers in cancer treatment. Immunother Adv. 2023;3:ltad013. [DOI] [PubMed] [PMC]

124.

Kanesvaran R, Cordoba R, Maggiore R. Immunotherapy in Older Adults With Advanced Cancers: Implications for Clinical Decision-Making and Future Research. Am Soc Clin Oncol Educ Book. 2018;38:400–14. [DOI] [PubMed]

125.

Ullrich F, Bröckelmann PJ, Turki AT, Khan AM, Chiru ED, Vetter M, et al. Impact of immunological aging on T cell-mediated therapies in older adults with multiple myeloma and lymphoma. J Immunother Cancer. 2024;12:e009462. [DOI] [PubMed] [PMC]

126.

Rached L, Geraud A, Frelaut M, Ap Thomas Z, Goldschmidt V, Beraud-Chaulet G, et al. Antibody drug conjugates in older patients: State of the art. Crit Rev Oncol Hematol. 2024;193:104212. [DOI] [PubMed]

127.

Choi S, Byun JM, Park SS, Han J, Oh S, Jung S, et al. Efficacy and Safety of Bispecific T-Cell Engagers in Relapsed/Refractory Multiple Myeloma: A Real-World Data-Based Case-Controlled Study. Transplant Cell Ther. 2025;31:74.e1–11. [DOI] [PubMed]