Table 1.

Examples of antibody-drug conjugates in late clinical development (grouped by conjugation methods and drug release mechanisms).

ADC name	Target	Cytotoxic drug	Therapeutic area	Current status
Linked to cysteines via maleimidocaproyl-VC dipeptide-PAB-MMAE and cleavage by cathepsin B
Brentuximab vedotin	CD30	MMAE	HL, ALCL	Approved (2011)
CDX-011 (Glembatumumab vedotin)	GPNMB	MMAE	Breast cancer melanoma	Phase 2
RG-7593 (Pinatuzuumab vedotin) DCDT2980S	CD22	MMAE	DLBL, follicular non-Hodgkin’s lymphoma	Phase 2
PSMA-ADC	PSMA	MMAE	Prostate cancer	Phase 2
Linked to lysines via SMCC thioether and released by proteolytic degradation of antibody
Trastuzumab emtansine	Her2	Maytansinoid DM1	Metastatic breast cancer	Approved (2013)
Milatuzumab-dox	CD74	doxorubicin	Multiple myeloma	Phase 2
Linked to lysines via acetyl butyrate hydrazone and released by hydrolysis at low pH
Gemtuzumab ozogamicin	CD33	N-acetyl- γ calicheamicin	AML	withdrawn
Inotuzumab ozogamincin	CD22	N-acetyl- γ calicheamicin	NHL, ALL	Phase 3
Linked to lysines via hindered disulfide bond in SPDB and released by reductive cleavage
BT062	CD138	maytansinoid	Multiple myeloma	Phase 2
SAR3419	CD19	maytanisinoid	DLBL, ALL	Phase 2
Lorvotuzumab mertansine (IMGN-901)	CD56	maytanisinoid	Small-cell lung cancer	Phase 2 *

Abbreviations: MMAE, monomethylauristatin E; VC, valine citrulline; SMCC, 4-(-maleimidomethyl)cyclohexanecarboxylic acid N-hydroxysuccinimide ester; SPDB, N-succinimidyl 3-(2-pyridyldithiol)butyrate; SPP, N-succinimidyl 4-(2-pyridyldithio)pentanoate; HL, Hodgkin lymphoma; ALCL, anaplastic large-cell lymphoma; AML, acute myeloid leukemia; NHL, non-Hodgkin lymphoma; ALL, acute lymphocytic leukemia; DLBL, diffuse large B-cell lymphoma; GPNMB, glycoprotein nonmetastatic B; PSMA, prostate-specific membrane antigen; * Lorvotuzumab phase 2 studied has been discontinued.