Table Info

Table 1.

Current clinical data on ADCs in NSCLC

Target	Drug	Trial, phase	Outcomes
cHER2	Trastuzumab deruxtecan (T-DXd)	DESTINY-Lung01 [36, 37] (6.4 mg/kg) N = 91 Phase 2	ORR 54.9% DOR 10.6 mo mPFS 8.2 mo mOS 18.6 mo DCR 92%
	Trastuzumab deruxtecan (T-DXd)	DESTINY-Lung02 [38] (5.4 mg/kg vs. 6.4 mg/kg) N = 101 vs. 50 Phase 2	5.4 mg/kg vs. 6.4 mg/kg: ORR 53.8% vs. 42.9% DOR NE vs. 5.9 mo DCR 90.4% vs. 92.9%
	Ado-trastuzumab emtansine (TDM1)	JapicCTI-194620 [39] N = 22, HER2 exon-20 mutation Phase 2	ORR 38.1% DOR 3.5 mo mPFS 2.8 mo mOS 8.1 mo DCR 52.4%
	Ado-trastuzumab emtansine (TDM1)	NCT02289833 [40] (IHC 2+ vs. 3+) N = 29 vs. 20 Phase 2	IHC 2+ vs. 3+: ORR NE vs. 20% mPFS 2.6 mo vs. 2.7 mo mOS 12.2 mo vs. 15.3 mo
	Zanidatamab zovodotin (ZW49)	NCT03821233 [41] Phase 1 Reported for multiple cancer types	ORR 28% DCR 72%
HER3	Patritzumab deruxtecan (HER3-DXd)	NCT03260491 [42, 43] (EGFR-WT vs. EGFRm) N = 47 vs. 57 Phase 1	EGFR-WT vs. EGFRm: ORR N/A vs. 39% DOR 5.7 mo vs. 6.4 mo DCR 28% vs. 72% mPFS 5.4 mo vs. 8.2 mo
HER3	Patritzumab deruxtecan (HER3-DXd)	HERTHENA-Lung01 [44] N = 225, EGFRm Phase 2	ORR 29.8% DOR 6.4 mo mPFS 5.5 mo mOS 11.9 mo
Trop-2	Datopotamab deruxtecan (Dato-DXd)	TROPION-PanTumor01 [45] N = 210 Phase 1	ORR 26% DOR 10.5 mo mPFS 6.9 mo mOS 11.4 mo
		TROPION-Lung02 [46] (Dato-DXd plus pembrolizumab doublet vs. Dato-DXd plus pembro plus Pt-CT) N = 20 vs. 42 Phase 1B	pembrolizumab vs. pembrolizumab plus CT: ORR 60% vs. 55% DCR 85% vs. 85%
		TROPION-Lung01 [47] (Dato-DXd vs. docetaxel) N = 299 vs. 305 Phase 3	Dato-DXd vs. docetaxel: ORR 26.4% vs. 12.8% DOR 7.1 mo vs. 5.6 mo mPFS 4.4 mo vs. 3.7 mo mOS 12.4 mo vs. 11 mo
		TROPION-Lung05 [48] N = 137, actionable mutations Phase 2	ORR 35.8% DOR 7 mo mOS 15.2 mo DCR 78.8%
	Sacituzumab govitecan (SG)	TROPiCS-03 [49] N = 54 Phase 1/2	ORR 16.7% DOR 6.0 mo mPFS 4.4 mo mOS 7.3 mo
	Sacituzumab tirumotecan SKB264	NCT04152499 [50] N = 43 Phase 2	EGFRm vs. EGFR-WT: ORR 60.0% vs. 26.3% mDOR 8.7 mo vs. 9.6 mo mPFS 11.5 mo vs. 5.3 mo mOS 22.7 mo vs. 14.1 mo
c-Met	Telisotuzumab vedotin (Teliso-V)	LUMINOSITY [51] N = 136 Phase 2	NSQ vs. SQ: ORR 36.5% vs. 11.1% DOR 6.9 mo vs. 4.4 mo
c-Met	ABBV-400	NCT05029882 [52] N = 57 Phase 1	ORR 43.8%
CEACAM5	Tusamitamab ravtansine	NCT02187848 [53] (high expressor ≥ 50% vs. moderate 1–50%) N = 64 vs. 28, NSQ Phase 1/2	High expressor: ORR 20.3% Moderate: ORR 7.1%
B7-H3	DS-7300	NCT04145622 [54] N = 5, SQ Phase 1/2	40% response DCR 80%

CEACAM5: cell adhesion molecule 5; HER2: human epidermal growth factor receptor 2; ADCs: antibody-drug conjugates; ORR: overall response rate; DOR: duration of response; mPFS: median progression-free survival; mOS: median overall survival; DCR: disease control rate; IHC: immunohistochemistry; EGFRm: EGFR-mutated; EGFR-WT: EGFR wild type; CT: chemotherapy; NSCLC: non-small cell lung cancer; NSQ: non-squamous; SQ: squamous; Trop-2: trophoblast cell-surface antigen 2; NE: not estimable

Declarations

Author contributions

KW: Conceptualization, Investigation, Writing—original draft, Writing—review & editing, Validation. AL: Conceptualization, Investigation, Writing—original draft, Validation. RH: Conceptualization, Investigation, Writing—original draft, Writing—review & editing, Validation, Supervision.

Conflicts of interest

RH is a consultant for Targeted Oncology and Takeda and received honoraria from DAVA Oncology, Targeted Oncology, and The Dedham Group. Both 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

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