Table 1.

Clinical trials evaluating antibody–drug conjugates in patients with NSCLC harboring HER2 aberrations. NSCLC, non-small cell lung cancer; HER2, human epidermal growth factor receptor 2; DAR, drug-to-antibody ratio; ORR, objective response rate; PFS, progression-free survival; CI, confidence intervals; OS, overall survival; TRAE, treatment-related adverse event; IHC, immunohistochemistry; FISH, fluorescence in situ hybridization; NE, not evaluable; NA, not available; NR, not reached.

Agent	Antibody; Chemotherapeutic	Study	Phase	n	Prior Systemic Therapy	HER2 Positivity Definition	ORR n (%)	PFS in Months Median (95% CI)	OS in Months Median (95% CI)	Most Common Grade 3 or Higher TRAE (%)
T-DM1	Trastuzumab; emtansine	Hotta et al. [20].	2	15	Yes	IHC 3+, 2+/FISH+, or exon 20 mutation	1 (6.7)	2.0 (1.4–4.0)	10.9 (4.4–12.0)	Thrombocytopenia (40.0)
T-DM1	Trastuzumab; emtansine	Peters et al. [22].	2	29; 20	Yes	IHC 2+; IHC 3+	0 (0); 4 (20)	2.6 (1.4–2.8); 2.7 (1.4–8.3)	12.2 (3.8–23.3); 15.3 (4.1-NE)	NA
T-DM1	Trastuzumab; emtansine	Li et al. [10]	2	49	Yes	Activating mutation or amplification	25 (51.0)	5.0 (3.5–5.9)	NA	Thrombocytopenia (6.0), Anemia (6.0)
T-DM1	Trastuzumab; emtansine	Iwama et al. [32]	2	22	Yes	Exon 20 insertion mutation	8 (38.1)	2.8 (1.4–4.4)	8.1 (3.5–13.2)	Thrombocytopenia (18.2)
T-DXd	Trastuzumab; deruxtecan	Tsurutani et al. [23]	1	18	Yes	IHC 1+, 2+, 3+ or amplification	10 (55.6)	11.3 (5.5–14.1)	NR (17.3-NE)	NA
T-DXd	Trastuzumab; deruxtecan	Li et al. [12].	1	91	Yes	Mutation	50 (54.9)	8.2 (6.0–11.9)	17.8 (13.8–22.1)	Neutropenia (19.0)
T-DXd	Trastuzumab; deruxtecan	Nakagawa et al. [11]	1	49	Yes	IHC 2+, 3+	12 (24.5)	5.4 (2.8–7.0)	NA	Neutropenia (20.4)
T-DXd	Trastuzumab; deruxtecan	Goto et al. [1]	2	52 (5.4 mg/kg); 28 (6.4 mg/kg)	Yes	Mutation	28 (53.8); 12 (42.9)	NA	NA	NA