Exploration of Targeted Anti-tumor Therapy

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%

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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

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