ADC ID	DRG0PXQWR
ADC Name	Depatuxizumab mafodotin
Synonyms	depatuxizumab mafodotin; ABT-414; Depatux-M; ABBV-414    Click to Show/Hide
Organization	AbbVie (Top20 MNC) (Originator);Life Science Pharmaceuticals (Originator)
Drug Status	Phase 3 (discontinued)
Drug-to-Antibody Ratio	3.8
Structure
				2D MOL
Antibody Name	Depatuxizumab					Antibody Info
Antigen Name	Epidermal growth factor receptor (EGFR)					Antigen Info
Payload Name	MMAF					Payload Info
Therapeutic Target	Microtubule (MT)					Target Info
Linker Name	Maleimido-caproyl					Linker Info
Conjugate Type	Random Cysteines
Combination Type	mafodotin

Bystander Killing Effect	Description	Reference
no	Because Cys-mc-MMAF released from Depatux-M lacks potential, toxin levels were not measured in the corresponding conditioned media.	[4]

Standard Type	Value	Units	Description	Reference
Maximum Observed Concentration (Cmax)	21.6	ug/mL	Geometric mean (Mean, % CV) pharmacokinetic (PK) parameters of depatux-m, total depatux, and Cys-mafodotin following first IV administration of depatux-m at 1 mg/kg.	[1]
Area Under the Concentration-Time Curve (AUC)	2.62	mg*h/mL	Geometric mean (Mean, % CV) pharmacokinetic (PK) parameters of depatux-m, total depatux, and Cys-mafodotin following first IV administration of depatux-m at 1 mg/kg, AUC 21 days.	[1]
Area Under the Concentration-Time Curve (AUC)	3.03	mg*h/mL	Geometric mean (Mean, % CV) pharmacokinetic (PK) parameters of depatux-m, total depatux, and Cys-mafodotin following first IV administration of depatux-m at 1 mg/kg, AUC ∞.	[1]
Maximum Observed Concentration (Cmax)	50.4	ug/mL	Geometric mean (Mean, % CV) pharmacokinetic (PK) parameters of depatux-m, total depatux, and Cys-mafodotin following first IV administration of depatux-m at 2 mg/kg.	[1]
Area Under the Concentration-Time Curve (AUC)	7.45	mg*h/mL	Geometric mean (Mean, % CV) pharmacokinetic (PK) parameters of depatux-m, total depatux, and Cys-mafodotin following first IV administration of depatux-m at 2 mg/kg, AUC 21 days.	[1]
Area Under the Concentration-Time Curve (AUC)	10.1	mg*h/mL	Geometric mean (Mean, % CV) pharmacokinetic (PK) parameters of depatux-m, total depatux, and Cys-mafodotin following first IV administration of depatux-m at 2 mg/kg, AUC ∞.	[1]
Maximum Observed Concentration (Cmax)	58.3	ug/mL	Geometric mean (Mean, % CV) pharmacokinetic (PK) parameters of depatux-m, total depatux, and Cys-mafodotin following first IV administration of depatux-m at 3 mg/kg.	[1]
Area Under the Concentration-Time Curve (AUC)	7.79	mg*h/mL	Geometric mean (Mean, % CV) pharmacokinetic (PK) parameters of depatux-m, total depatux, and Cys-mafodotin following first IV administration of depatux-m at 3 mg/kg, AUC 21 days.	[1]
Area Under the Concentration-Time Curve (AUC)	9.72	mg*h/mL	Geometric mean (Mean, % CV) pharmacokinetic (PK) parameters of depatux-m, total depatux, and Cys-mafodotin following first IV administration of depatux-m at 3 mg/kg, AUC ∞.	[1]
Maximum Observed Concentration (Cmax)	106	ug/mL	Geometric mean (Mean, % CV) pharmacokinetic (PK) parameters of depatux-m, total depatux, and Cys-mafodotin following first IV administration of depatux-m at 4 mg/kg.	[1]
Area Under the Concentration-Time Curve (AUC)	13.1	mg*h/mL	Geometric mean (Mean, % CV) pharmacokinetic (PK) parameters of depatux-m, total depatux, and Cys-mafodotin following first IV administration of depatux-m at 4 mg/kg, AUC 21 days.	[1]
Area Under the Concentration-Time Curve (AUC)	18.1	mg*h/mL	Geometric mean (Mean, % CV) pharmacokinetic (PK) parameters of depatux-m, total depatux, and Cys-mafodotin following first IV administration of depatux-m at 4 mg/kg, AUC ∞.	[1]
Maximum Observed Concentration (Cmax)	19.6	ug/mL	PK parameters of depatux-m after 0.5 mg/kg depatux-m dosing on day 1 of cycle 2	[2]
Area Under the Concentration-Time Curve (AUC)	3.52	mg/h/mL	PK parameters of depatux-m after 0.5 mg/kg depatux-m dosing on day 1 of cycle 2, AUC 14 days	[2]
Maximum Observed Concentration (Cmax)	44.1	ug/mL	PK parameters of depatux-m after 1.0 mg/kg depatux-m dosing on day 1 of cycle 2	[2]
Area Under the Concentration-Time Curve (AUC)	7.11	mg/h/mL	PK parameters of depatux-m after 1.0 mg/kg depatux-m dosing on day 1 of cycle 2, AUC 14 days	[2]
Maximum Observed Concentration (Cmax)	51.1	ug/mL	PK parameters of depatux-m after 1.25 mg/kg depatux-m dosing on day 1 of cycle 2	[2]
Area Under the Concentration-Time Curve (AUC)	9.14	mg/h/mL	PK parameters of depatux-m after 1.25 mg/kg depatux-m dosing on day 1 of cycle 2, AUC 14 days	[2]
Maximum Observed Concentration (Cmax)	70.5	ug/mL	PK parameters of depatux-m after 1.5 mg/kg depatux-m dosing on day 1 of cycle 2	[2]
Area Under the Concentration-Time Curve (AUC)	10.2	mg/h/mL	PK parameters of depatux-m after 1.5 mg/kg depatux-m dosing on day 1 of cycle 2, AUC 14 days	[2]

Standard Type	Value	Units	Description	Reference
Area Under the Concentration-Time Curve (AUC)	2.62	mg*h/mL	Geometric mean (Mean, % CV) pharmacokinetic (PK) parameters of depatux-m, total depatux, and Cys-mafodotin following first IV administration of depatux-m at 1 mg/kg, AUC 21 days.	[1]
Area Under the Concentration-Time Curve (AUC)	3.03	mg*h/mL	Geometric mean (Mean, % CV) pharmacokinetic (PK) parameters of depatux-m, total depatux, and Cys-mafodotin following first IV administration of depatux-m at 1 mg/kg, AUC ∞.	[1]
Area Under the Concentration-Time Curve (AUC)	7.45	mg*h/mL	Geometric mean (Mean, % CV) pharmacokinetic (PK) parameters of depatux-m, total depatux, and Cys-mafodotin following first IV administration of depatux-m at 2 mg/kg, AUC 21 days.	[1]
Area Under the Concentration-Time Curve (AUC)	10.1	mg*h/mL	Geometric mean (Mean, % CV) pharmacokinetic (PK) parameters of depatux-m, total depatux, and Cys-mafodotin following first IV administration of depatux-m at 2 mg/kg, AUC ∞.	[1]
Area Under the Concentration-Time Curve (AUC)	7.79	mg*h/mL	Geometric mean (Mean, % CV) pharmacokinetic (PK) parameters of depatux-m, total depatux, and Cys-mafodotin following first IV administration of depatux-m at 3 mg/kg, AUC 21 days.	[1]
Area Under the Concentration-Time Curve (AUC)	9.72	mg*h/mL	Geometric mean (Mean, % CV) pharmacokinetic (PK) parameters of depatux-m, total depatux, and Cys-mafodotin following first IV administration of depatux-m at 3 mg/kg, AUC ∞.	[1]
Area Under the Concentration-Time Curve (AUC)	13.1	mg*h/mL	Geometric mean (Mean, % CV) pharmacokinetic (PK) parameters of depatux-m, total depatux, and Cys-mafodotin following first IV administration of depatux-m at 4 mg/kg, AUC 21 days.	[1]
Area Under the Concentration-Time Curve (AUC)	18.1	mg*h/mL	Geometric mean (Mean, % CV) pharmacokinetic (PK) parameters of depatux-m, total depatux, and Cys-mafodotin following first IV administration of depatux-m at 4 mg/kg, AUC ∞.	[1]
Area Under the Concentration-Time Curve (AUC)	3.52	mg/h/mL	PK parameters of depatux-m after 0.5 mg/kg depatux-m dosing on day 1 of cycle 2, AUC 14 days	[2]
Area Under the Concentration-Time Curve (AUC)	7.11	mg/h/mL	PK parameters of depatux-m after 1.0 mg/kg depatux-m dosing on day 1 of cycle 2, AUC 14 days	[2]
Area Under the Concentration-Time Curve (AUC)	9.14	mg/h/mL	PK parameters of depatux-m after 1.25 mg/kg depatux-m dosing on day 1 of cycle 2, AUC 14 days	[2]
Area Under the Concentration-Time Curve (AUC)	10.2	mg/h/mL	PK parameters of depatux-m after 1.5 mg/kg depatux-m dosing on day 1 of cycle 2, AUC 14 days	[2]

Standard Type	Value	Units	Description	Reference
Area Under the Concentration-Time Curve (AUC)	2.62	mg*h/mL	Geometric mean (Mean, % CV) pharmacokinetic (PK) parameters of depatux-m, total depatux, and Cys-mafodotin following first IV administration of depatux-m at 1 mg/kg, AUC 21 days.	[1]
Area Under the Concentration-Time Curve (AUC)	3.03	mg*h/mL	Geometric mean (Mean, % CV) pharmacokinetic (PK) parameters of depatux-m, total depatux, and Cys-mafodotin following first IV administration of depatux-m at 1 mg/kg, AUC ∞.	[1]
Area Under the Concentration-Time Curve (AUC)	7.45	mg*h/mL	Geometric mean (Mean, % CV) pharmacokinetic (PK) parameters of depatux-m, total depatux, and Cys-mafodotin following first IV administration of depatux-m at 2 mg/kg, AUC 21 days.	[1]
Area Under the Concentration-Time Curve (AUC)	10.1	mg*h/mL	Geometric mean (Mean, % CV) pharmacokinetic (PK) parameters of depatux-m, total depatux, and Cys-mafodotin following first IV administration of depatux-m at 2 mg/kg, AUC ∞.	[1]
Area Under the Concentration-Time Curve (AUC)	7.79	mg*h/mL	Geometric mean (Mean, % CV) pharmacokinetic (PK) parameters of depatux-m, total depatux, and Cys-mafodotin following first IV administration of depatux-m at 3 mg/kg, AUC 21 days.	[1]
Area Under the Concentration-Time Curve (AUC)	9.72	mg*h/mL	Geometric mean (Mean, % CV) pharmacokinetic (PK) parameters of depatux-m, total depatux, and Cys-mafodotin following first IV administration of depatux-m at 3 mg/kg, AUC ∞.	[1]
Area Under the Concentration-Time Curve (AUC)	13.1	mg*h/mL	Geometric mean (Mean, % CV) pharmacokinetic (PK) parameters of depatux-m, total depatux, and Cys-mafodotin following first IV administration of depatux-m at 4 mg/kg, AUC 21 days.	[1]
Area Under the Concentration-Time Curve (AUC)	18.1	mg*h/mL	Geometric mean (Mean, % CV) pharmacokinetic (PK) parameters of depatux-m, total depatux, and Cys-mafodotin following first IV administration of depatux-m at 4 mg/kg, AUC ∞.	[1]
Area Under the Concentration-Time Curve (AUC)	3.52	mg/h/mL	PK parameters of depatux-m after 0.5 mg/kg depatux-m dosing on day 1 of cycle 2, AUC 14 days	[2]
Area Under the Concentration-Time Curve (AUC)	7.11	mg/h/mL	PK parameters of depatux-m after 1.0 mg/kg depatux-m dosing on day 1 of cycle 2, AUC 14 days	[2]
Area Under the Concentration-Time Curve (AUC)	9.14	mg/h/mL	PK parameters of depatux-m after 1.25 mg/kg depatux-m dosing on day 1 of cycle 2, AUC 14 days	[2]
Area Under the Concentration-Time Curve (AUC)	10.2	mg/h/mL	PK parameters of depatux-m after 1.5 mg/kg depatux-m dosing on day 1 of cycle 2, AUC 14 days	[2]

Standard Type	Value	Units	Description	Reference
Area Under the Concentration-Time Curve (AUC)	2.62	mg*h/mL	Geometric mean (Mean, % CV) pharmacokinetic (PK) parameters of depatux-m, total depatux, and Cys-mafodotin following first IV administration of depatux-m at 1 mg/kg, AUC 21 days.	[1]
Area Under the Concentration-Time Curve (AUC)	3.03	mg*h/mL	Geometric mean (Mean, % CV) pharmacokinetic (PK) parameters of depatux-m, total depatux, and Cys-mafodotin following first IV administration of depatux-m at 1 mg/kg, AUC ∞.	[1]
Elimination Half-Life (t1/2)	7.3	day	Geometric mean (Mean, % CV) pharmacokinetic (PK) parameters of depatux-m, total depatux, and Cys-mafodotin following first IV administration of depatux-m at 1 mg/kg.	[1]
Clearance (CL)	0.363	mL/h/kg	Geometric mean (Mean, % CV) pharmacokinetic (PK) parameters of depatux-m, total depatux, and Cys-mafodotin following first IV administration of depatux-m at 1 mg/kg.	[1]
Area Under the Concentration-Time Curve (AUC)	7.45	mg*h/mL	Geometric mean (Mean, % CV) pharmacokinetic (PK) parameters of depatux-m, total depatux, and Cys-mafodotin following first IV administration of depatux-m at 2 mg/kg, AUC 21 days.	[1]
Area Under the Concentration-Time Curve (AUC)	10.1	mg*h/mL	Geometric mean (Mean, % CV) pharmacokinetic (PK) parameters of depatux-m, total depatux, and Cys-mafodotin following first IV administration of depatux-m at 2 mg/kg, AUC ∞.	[1]
Elimination Half-Life (t1/2)	11.1	day	Geometric mean (Mean, % CV) pharmacokinetic (PK) parameters of depatux-m, total depatux, and Cys-mafodotin following first IV administration of depatux-m at 2 mg/kg.	[1]
Clearance (CL)	0.206	mL/h/kg	Geometric mean (Mean, % CV) pharmacokinetic (PK) parameters of depatux-m, total depatux, and Cys-mafodotin following first IV administration of depatux-m at 2 mg/kg.	[1]
Area Under the Concentration-Time Curve (AUC)	7.79	mg*h/mL	Geometric mean (Mean, % CV) pharmacokinetic (PK) parameters of depatux-m, total depatux, and Cys-mafodotin following first IV administration of depatux-m at 3 mg/kg, AUC 21 days.	[1]
Area Under the Concentration-Time Curve (AUC)	9.72	mg*h/mL	Geometric mean (Mean, % CV) pharmacokinetic (PK) parameters of depatux-m, total depatux, and Cys-mafodotin following first IV administration of depatux-m at 3 mg/kg, AUC ∞.	[1]
Elimination Half-Life (t1/2)	8.7	day	Geometric mean (Mean, % CV) pharmacokinetic (PK) parameters of depatux-m, total depatux, and Cys-mafodotin following first IV administration of depatux-m at 3 mg/kg.	[1]
Clearance (CL)	0.364	mL/h/kg	Geometric mean (Mean, % CV) pharmacokinetic (PK) parameters of depatux-m, total depatux, and Cys-mafodotin following first IV administration of depatux-m at 3 mg/kg.	[1]
Area Under the Concentration-Time Curve (AUC)	13.1	mg*h/mL	Geometric mean (Mean, % CV) pharmacokinetic (PK) parameters of depatux-m, total depatux, and Cys-mafodotin following first IV administration of depatux-m at 4 mg/kg, AUC 21 days.	[1]
Area Under the Concentration-Time Curve (AUC)	18.1	mg*h/mL	Geometric mean (Mean, % CV) pharmacokinetic (PK) parameters of depatux-m, total depatux, and Cys-mafodotin following first IV administration of depatux-m at 4 mg/kg, AUC ∞.	[1]
Elimination Half-Life (t1/2)	12	day	Geometric mean (Mean, % CV) pharmacokinetic (PK) parameters of depatux-m, total depatux, and Cys-mafodotin following first IV administration of depatux-m at 4 mg/kg.	[1]
Clearance (CL)	0.226	mL/h/kg	Geometric mean (Mean, % CV) pharmacokinetic (PK) parameters of depatux-m, total depatux, and Cys-mafodotin following first IV administration of depatux-m at 4 mg/kg.	[1]
Area Under the Concentration-Time Curve (AUC)	3.52	mg/h/mL	PK parameters of depatux-m after 0.5 mg/kg depatux-m dosing on day 1 of cycle 2, AUC 14 days	[2]
Elimination Half-Life (t1/2)	10.9	day	PK parameters of depatux-m after 0.5 mg/kg depatux-m dosing on day 1 of cycle 2	[2]
Clearance (CL)	0.143	mL/h/kg	PK parameters of depatux-m after 0.5 mg/kg depatux-m dosing on day 1 of cycle 2	[2]
Area Under the Concentration-Time Curve (AUC)	7.11	mg/h/mL	PK parameters of depatux-m after 1.0 mg/kg depatux-m dosing on day 1 of cycle 2, AUC 14 days	[2]
Elimination Half-Life (t1/2)	9.2	day	PK parameters of depatux-m after 1.0 mg/kg depatux-m dosing on day 1 of cycle 2	[2]
Clearance (CL)	0.151	mL/h/kg	PK parameters of depatux-m after 1.0 mg/kg depatux-m dosing on day 1 of cycle 2	[2]
Area Under the Concentration-Time Curve (AUC)	9.14	mg/h/mL	PK parameters of depatux-m after 1.25 mg/kg depatux-m dosing on day 1 of cycle 2, AUC 14 days	[2]
Elimination Half-Life (t1/2)	11.2	day	PK parameters of depatux-m after 1.25 mg/kg depatux-m dosing on day 1 of cycle 2	[2]
Clearance (CL)	0.146	mL/h/kg	PK parameters of depatux-m after 1.25 mg/kg depatux-m dosing on day 1 of cycle 2	[2]
Area Under the Concentration-Time Curve (AUC)	10.2	mg/h/mL	PK parameters of depatux-m after 1.5 mg/kg depatux-m dosing on day 1 of cycle 2, AUC 14 days	[2]
Elimination Half-Life (t1/2)	7.4	day	PK parameters of depatux-m after 1.5 mg/kg depatux-m dosing on day 1 of cycle 2	[2]
Clearance (CL)	0.154	mL/h/kg	PK parameters of depatux-m after 1.5 mg/kg depatux-m dosing on day 1 of cycle 2	[2]
Clearance (CL)	0.187	L/day	Population Estimates from the Final Individual Model	[3]

Standard Type	NCT Number	Clinical Status	Clinical Trial Description
Progression Free Survival	NCT02590263	PHASE1|||PHASE2	A Non-Randomized, Open-Label, Multi-Center Phase 1/2 Study Evaluating the Safety, Pharmacokinetics and Efficacy of ABT-414 in Japanese Subjects With Malignant Glioma
Overall suvival (OS)	NCT02590263	PHASE1|||PHASE2	A Non-Randomized, Open-Label, Multi-Center Phase 1/2 Study Evaluating the Safety, Pharmacokinetics and Efficacy of ABT-414 in Japanese Subjects With Malignant Glioma
Overall suvival (OS)	NCT02573324	PHASE3	A Randomized, Placebo Controlled Phase 3 Study of ABT-414 With Concurrent Chemoradiation and Adjuvant Temozolomide in Subjects With Newly Diagnosed Glioblastoma (GBM) With Epidermal Growth Factor Receptor (EGFR) Amplification (Intellance1)    Click to Show/Hide
During of response (DoR)	NCT02590263	PHASE1|||PHASE2	A Non-Randomized, Open-Label, Multi-Center Phase 1/2 Study Evaluating the Safety, Pharmacokinetics and Efficacy of ABT-414 in Japanese Subjects With Malignant Glioma
Undisclosed	NCT01741727	PHASE1	A Phase 1/2 Study Evaluating the Safety, Pharmacokinetics and Efficacy of ABT-414 in Subjects With Advanced Solid Tumors Likely to Over-Express the Epidermal Growth Factor Receptor (EGFR)
Undisclosed	NCT02343406	PHASE2	INTELLANCE-2: ABT-414 Alone or ABT-414 Plus Temozolomide Versus Lomustine or Temozolomide for Recurrent Glioblastoma: A Randomized Phase 2 Study of the EORTC Brain Tumor Group
Undisclosed	NCT03419403	PHASE3	Phase 3b Study for Management of Ocular Side Effects in Subjects With EGFR-amplified Glioblastoma Receiving Depatuxizumab Mafodotin (ABT-414)
Undisclosed	NCT01800695	PHASE1	A Phase 1 Study Evaluating the Safety and Pharmacokinetics of ABT-414 for Subjects With Glioblastoma Multiforme
Undisclosed	NCT03123952	N.A.	This is an expanded access program (EAP) for eligible participants. This program is designed to provide access to ABT-414 prior to approval by the local regulatory agency. Availability will depend on territory eligibility. Participating sites will be added as they apply for and are approved for the EAP. A medical doctor must decide whether the potential benefit outweighs the risk of receiving an investigational therapy based on the individual patient's medical history and program eligibility criteria.    Click to Show/Hide
Median progression-free survival (mPFS)	Undisclosed	Undisclosed	Undisclosed
Median Overall Survival (mOS)	Undisclosed	Undisclosed	Undisclosed

Standard Type	Value	Units	Cell Line	Disease Model
Tumor Growth Inhibition value (TGI)	≈ 87.5	%	MSTO-211H cells	Pleural biphasic mesothelioma
Half Maximal Inhibitory Concentration (IC50)	10.00 - 35.00	ug/mL	NCI-H2052 cells	Pleural mesothelioma
Half Maximal Inhibitory Concentration (IC50)	10.00 - 35.00	ug/mL	NCI-H2052 cells	Pleural mesothelioma
Half Maximal Inhibitory Concentration (IC50)	10.00 - 35.00	ug/mL	NCI-H28 cells	Pleural mesothelioma
Half Maximal Inhibitory Concentration (IC50)	10.00 - 35.00	ug/mL	MSTO-211H cells	Pleural biphasic mesothelioma

Experiment 1 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Progression Free Survival	2.1 months
Patients Enrolled	Japanese participants with WHO grade III or IV malignant glioma
Administration Dosage	ABT-414 administered every other weeks monotherapy
Related Clinical Trial
NCT Number	NCT02590263	Clinical Status	PHASE1|||PHASE2
Clinical Description	A Non-Randomized, Open-Label, Multi-Center Phase 1/2 Study Evaluating the Safety, Pharmacokinetics and Efficacy of ABT-414 in Japanese Subjects With Malignant Glioma
Primary Endpoint	For all patients in the 2L Depatux-M + CT arm, the 6-month PFS estimate by central review was 25.6% (95% CI 11.4-42.6) with a median PFS of 2.1 months (95% CI 1.9-3.9; Figure 3 A, B). The 6-month OS estimate was 89.7% (95% CI 71.3-96.5), and the median OS was 14.7 months (95% CI 10.7-15.4; Figure 4). ORR, analyzed in patients with at least one measurable disease at baseline, was 21.7% (5/23) by central review with all responses being PR and the median DoR was 5.5 months (95% CI 1.9-NE; Table 6). Seven patients were considered to have 6-month PFS by investigator review, but not by central review.    Click to Show/Hide
Other Endpoint	Objective Response Rate [Time Frame: At each visit for approximately 1 year], Overall Survival [Time Frame: At each visit for approximately 1 year], Duration of Overall Response [Time Frame: At each visit for approximately 1 year]
Experiment 2 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Overall suvival (OS)	14.7 months
Patients Enrolled	Japanese participants with WHO grade III or IV malignant glioma
Administration Dosage	ABT-414 administered every other weeks monotherapy
Related Clinical Trial
NCT Number	NCT02590263	Clinical Status	PHASE1|||PHASE2
Clinical Description	A Non-Randomized, Open-Label, Multi-Center Phase 1/2 Study Evaluating the Safety, Pharmacokinetics and Efficacy of ABT-414 in Japanese Subjects With Malignant Glioma
Primary Endpoint	For all patients in the 2L Depatux-M + CT arm, the 6-month PFS estimate by central review was 25.6% (95% CI 11.4-42.6) with a median PFS of 2.1 months (95% CI 1.9-3.9; Figure 3 A, B). The 6-month OS estimate was 89.7% (95% CI 71.3-96.5), and the median OS was 14.7 months (95% CI 10.7-15.4; Figure 4). ORR, analyzed in patients with at least one measurable disease at baseline, was 21.7% (5/23) by central review with all responses being PR and the median DoR was 5.5 months (95% CI 1.9-NE; Table 6). Seven patients were considered to have 6-month PFS by investigator review, but not by central review.    Click to Show/Hide
Other Endpoint	Objective Response Rate [Time Frame: At each visit for approximately 1 year], Overall Survival [Time Frame: At each visit for approximately 1 year], Duration of Overall Response [Time Frame: At each visit for approximately 1 year]
Experiment 3 Reporting the Activity Date of This ADC					[6]
Efficacy Data	Overall suvival (OS)	15.5 months
Patients Enrolled	Must have a clinical diagnosis of glioblastoma (GBM).
Administration Dosage	Depatuxizumab mafodotin is given on Day 1 of Week 1, 3 and 5 along with the standard therapy of TMZ and radiation during the chemoradiation phase. Depatuxizumab mafodotin is given on Day 1 and 15 of each cycle along with TMZ (Days 1-5 of each cycle) per standard of care during the adjuvant phase.
Related Clinical Trial
NCT Number	NCT02573324	Clinical Status	PHASE3
Clinical Description	A Randomized, Placebo Controlled Phase 3 Study of ABT-414 With Concurrent Chemoradiation and Adjuvant Temozolomide in Subjects With Newly Diagnosed Glioblastoma (GBM) With Epidermal Growth Factor Receptor (EGFR) Amplification (Intellance1)
Primary Endpoint	Overall Survival (OS) [Time Frame: Overall median duration of follow-up was 15.5 months (range: 0.1, 35.6).]
Other Endpoint	OS for the O6-methylguaninemethlytransferese (MGMT) Unmethylated Group [Time Frame: Overall median duration of follow-up was 15.5 months (range: 0.1, 35.6).]
Experiment 4 Reporting the Activity Date of This ADC					[5]
Efficacy Data	During of response (DoR)	5.5 months
Patients Enrolled	Japanese participants with WHO grade III or IV malignant glioma
Administration Dosage	ABT-414 administered every other weeks monotherapy
Related Clinical Trial
NCT Number	NCT02590263	Clinical Status	PHASE1|||PHASE2
Clinical Description	A Non-Randomized, Open-Label, Multi-Center Phase 1/2 Study Evaluating the Safety, Pharmacokinetics and Efficacy of ABT-414 in Japanese Subjects With Malignant Glioma
Primary Endpoint	For all patients in the 2L Depatux-M + CT arm, the 6-month PFS estimate by central review was 25.6% (95% CI 11.4-42.6) with a median PFS of 2.1 months (95% CI 1.9-3.9; Figure 3 A, B). The 6-month OS estimate was 89.7% (95% CI 71.3-96.5), and the median OS was 14.7 months (95% CI 10.7-15.4; Figure 4). ORR, analyzed in patients with at least one measurable disease at baseline, was 21.7% (5/23) by central review with all responses being PR and the median DoR was 5.5 months (95% CI 1.9-NE; Table 6). Seven patients were considered to have 6-month PFS by investigator review, but not by central review.    Click to Show/Hide
Other Endpoint	Objective Response Rate [Time Frame: At each visit for approximately 1 year], Overall Survival [Time Frame: At each visit for approximately 1 year], Duration of Overall Response [Time Frame: At each visit for approximately 1 year]
Experiment 5 Reporting the Activity Date of This ADC					[7]
Patients Enrolled	Subjects must have a solid tumor type likely to over-express Epidermal Growth Factor Receptor (EGFR) (Phase 1)
Administration Dosage	Data from patients who received ABT-414 monotherapy at a dose of 1-4 mg/kg once every 3 weeks or 1 or 1.5 mg/kg weekly for 2 out of every 3 weeks (alternate schedule) by intravenous infusion were included in the analysis of triplicate 12-lead ECGs obtained before dosing and through 168 h after dosing.
Related Clinical Trial
NCT Number	NCT01741727	Clinical Status	PHASE1
Clinical Description	A Phase 1/2 Study Evaluating the Safety, Pharmacokinetics and Efficacy of ABT-414 in Subjects With Advanced Solid Tumors Likely to Over-Express the Epidermal Growth Factor Receptor (EGFR)
Primary Endpoint	Phase 1 - Safety (Number of subjects with adverse events and/or dose limiting toxicities) [Time Frame: Every 1-3 weeks for an average of 20 weeks]
Other Endpoint	Phase 2- Safety (Scheduled study visits occurring on average every 3 weeks) [Time Frame: Followed on average every 3 weeks for approximately 20 weeks]
Experiment 6 Reporting the Activity Date of This ADC					[8]
Patients Enrolled	Histologically confirmed de novo (primary) glioblastoma with unequivocal tumor progression or recurrence.
Administration Dosage	intravenous administration (1.25 mg/kg or 1.0 mg/kg body weight) over 30 to 40 minutes once every 2 weeks until one of the treatment withdrawal criteria was met. The dose was 1.25 mg/kg in the original protocol (Version 1) and Version 2, Amendment 1, and was lowered to 1.0 mg/kg in protocol Version 3, Amendment 2. Pediatric participants: Intravenous administration (1.0 mg/kg body weight for those who were 6 to 17 years old at the date of first dose, or 1.3 mg/kg for those who were 0 to 5 years old) over 30 to 40 minutes or as directed by the guidelines once every 2 weeks until one of the treatment withdrawal criteria was met, for a maximum of one year. If used in combination with temozolomide, depatuxizumab mafodotin was dosed on Day 1 and Day 15 of the TMZ cycle (assuming a standard regimen of 200 mg/m^2/day for 5 days of each 28-day cycle; for other TMZ schedules, timing of the depatuxizumab mafodotin dosing schedule were to be discussed with the medical monitor).    Click to Show/Hide
Related Clinical Trial
NCT Number	NCT02343406	Clinical Status	PHASE2
Clinical Description	INTELLANCE-2: ABT-414 Alone or ABT-414 Plus Temozolomide Versus Lomustine or Temozolomide for Recurrent Glioblastoma: A Randomized Phase 2 Study of the EORTC Brain Tumor Group
Primary Endpoint	Overall Survival (OS); Progression-Free Survival (PFS)
Other Endpoint	Objective Response Rate (ORR); Overall Survival in the Subgroup With Epidermal Growth Factor Receptor (EGFRvIII) Mutation
Experiment 7 Reporting the Activity Date of This ADC					[9]
Patients Enrolled	Newly diagnosed glioblastoma (GBM) histologically proven, World Health Organization (WHO) grade IV GBM or WHO grade IV gliosarcoma
Administration Dosage	During the Chemoradiation Phase, participants were to receive depatuxizumab mafodotin at 2.0 mg/kg IV infusion over 30 - 40 minutes once every 2 weeks (Day 1 of Weeks 1, 3, and 5 of the 6-week regimen). During the Adjuvant Therapy Phase, participants were to receive depatuxizumab mafodotin at 1.25 mg/kg on Day 1 (± 2 days) and Day 15 (± 2 days) of each 28-day cycle as a 30 - 40 minute infusion for 12 cycles.    Click to Show/Hide
Related Clinical Trial
NCT Number	NCT03419403	Clinical Status	PHASE3
Clinical Description	Phase 3b Study for Management of Ocular Side Effects in Subjects With EGFR-amplified Glioblastoma Receiving Depatuxizumab Mafodotin (ABT-414)
Primary Endpoint	Percentage of Participants Who Required a Change in Ocular Side Effect (OSE) Management [Time Frame: Within 8 weeks after the initial dose of depatuxizumab mafodotin]
Other Endpoint	Maximum Change From Baseline on the Logarithm of the Minimum Angle of Resolution (LogMAR) Scale; Time to Bandage Contact Lens (BCL) Intervention; Number of Participants With Depatuxizumab Mafodotin Dose Modifications Due to Ocular Side Effects (OSE)
Experiment 8 Reporting the Activity Date of This ADC					[10]
Patients Enrolled	Glioblastoma Multiforme (GBM)
Administration Dosage	ABT-414 will be administered by intravenous infusion
Related Clinical Trial
NCT Number	NCT01800695	Clinical Status	PHASE1
Clinical Description	A Phase 1 Study Evaluating the Safety and Pharmacokinetics of ABT-414 for Subjects With Glioblastoma Multiforme
Primary Endpoint	Number and percentage of participants with adverse events
Other Endpoint	Biomarker EGFR expression, Progression Free Survival, Overall Survival
Experiment 9 Reporting the Activity Date of This ADC					[11]
Patients Enrolled	Participant must have epidermal growth factor receptor (EGFR) amplification or EGFRvIII mutation.
Administration Dosage	.
Related Clinical Trial
NCT Number	NCT03123952	Clinical Status	N.A.
Clinical Description	This is an expanded access program (EAP) for eligible participants. This program is designed to provide access to ABT-414 prior to approval by the local regulatory agency. Availability will depend on territory eligibility. Participating sites will be added as they apply for and are approved for the EAP. A medical doctor must decide whether the potential benefit outweighs the risk of receiving an investigational therapy based on the individual patient's medical history and program eligibility criteria.
Experiment 10 Reporting the Activity Date of This ADC					[12]
Efficacy Data	Median progression-free survival (mPFS)	8.0 (depatux-m group); 6.3 (placebo group) Months	High EGFR expression (EGFR +++)
Patients Enrolled	EGFR-amp newly diagnosed GBM were randomized 1:1 to radiotherapy, temozolomide, and depatux-m/placebo.
Administration Dosage	Depatux-m was dosed at 2.0 mg/kg during RT, then 1.25 mg/kg thereafter on days 1 and 15/28, 19,21 and allowed to continue until disease progression.
Experiment 11 Reporting the Activity Date of This ADC					[12]
Efficacy Data	Median Overall Survival (mOS)	18.9 (depatux-m group); 18.7(placebo group) Months	High EGFR expression (EGFR +++)
Patients Enrolled	EGFR-amp newly diagnosed GBM were randomized 1:1 to radiotherapy, temozolomide, and depatux-m/placebo.
Administration Dosage	Depatux-m was dosed at 2.0 mg/kg during RT, then 1.25 mg/kg thereafter on days 1 and 15/2819, 21 and allowed to continue until disease progression.

Experiment 1 Reporting the Activity Date of This ADC					[13]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 87.50%	Positive EGFR expression (EGFR+++/++)
Method Description	To establish xenografts, 2 x 106 MSTO-211H cells mixed with 75-uL Matrigel were injected subcutaneously in the right flank of 5 to 6-week-old female BALB/c nu/nu miceFor the MSTO-211H study, mice received either ABT-414, ABBV-221 or ADC control (3 mg/kg) every 4 days.
In Vivo Model	MSTO-211H CDX model
In Vitro Model	Pleural biphasic mesothelioma	MSTO-211H cells		CVCL_1430
Experiment 2 Reporting the Activity Date of This ADC					[13]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	10.00 - 35.00 ug/mL	Positive EGFR expression (EGFR+++/++)
Method Description	Cells lines were plated at 1,000-3,000 cells per well in complete growth medium containing 10% FCS in 96-well plates and allowed to adhere overnight.
In Vitro Model	Pleural mesothelioma	NCI-H2052 cells		CVCL_1518
Experiment 3 Reporting the Activity Date of This ADC					[13]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	10.00 - 35.00 ug/mL	Positive EGFR expression (EGFR+++/++)
Method Description	Cells lines were plated at 1,000-3,000 cells per well in complete growth medium containing 10% FCS in 96-well plates and allowed to adhere overnight.
In Vitro Model	Pleural mesothelioma	NCI-H2052 cells		CVCL_1518
Experiment 4 Reporting the Activity Date of This ADC					[13]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	10.00 - 35.00 ug/mL	Positive EGFR expression (EGFR+++/++)
Method Description	Cells lines were plated at 1,000-3,000 cells per well in complete growth medium containing 10% FCS in 96-well plates and allowed to adhere overnight.
In Vitro Model	Pleural mesothelioma	NCI-H28 cells		CVCL_1555
Experiment 5 Reporting the Activity Date of This ADC					[13]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	10.00 - 35.00 ug/mL	Positive EGFR expression (EGFR+++/++)
Method Description	Cells lines were plated at 1,000-3,000 cells per well in complete growth medium containing 10% FCS in 96-well plates and allowed to adhere overnight.
In Vitro Model	Pleural biphasic mesothelioma	MSTO-211H cells		CVCL_1430

Ref 1	Efficacy and safety results of depatuxizumab mafodotin (ABT-414) in patients with advanced solid tumors likely to overexpress epidermal growth factor receptor
Ref 2	Safety, pharmacokinetics, and antitumor response of depatuxizumab mafodotin as monotherapy or in combination with temozolomide in patients with glioblastoma
Ref 3	An Integrated Population Pharmacokinetic Model Versus Individual Models of Depatuxizumab Mafodotin, an Anti-EGFR Antibody Drug Conjugate, in Patients With Solid Tumors Likely to Overexpress EGFR
Ref 4	Bystander Effects, Pharmacokinetics, and Linker-Payload Stability of EGFR-Targeting Antibody-Drug Conjugates Losatuxizumab Vedotin and Depatux-M in Glioblastoma Models
Ref 5	Study Evaluating ABT-414 in Japanese Subjects With Malignant Glioma
Ref 6	A Study of ABT-414 in Participants With Newly Diagnosed Glioblastoma (GBM) With Epidermal Growth Factor Receptor (EGFR) Amplification
Ref 7	A Study of ABT-414 in Subjects With Solid Tumors
Ref 8	Adult Study: ABT-414 Alone or ABT-414 Plus Temozolomide vs. Lomustine or Temozolomide for Recurrent Glioblastoma Pediatric Study: Evaluation of ABT-414 in Children With High Grade Gliomas
Ref 9	UNITE Study: Understanding New Interventions With GBM ThErapy
Ref 10	Evaluating the Safety and Pharmacokinetics of ABT-414 for Subjects With Glioblastoma Multiforme
Ref 11	Expanded Access to ABT-414
Ref 12	Depatuxizumab mafodotin in EGFR-amplified newly diagnosed glioblastoma: A phase III randomized clinical trial. Neuro Oncol. 2023 Feb 14;25(2):339-350. doi: 10.1093/neuonc/noac173.
Ref 13	Targeting and Efficacy of Novel mAb806-Antibody-Drug Conjugates in Malignant Mesothelioma. Pharmaceuticals (Basel). 2020 Oct 2;13(10):289. doi: 10.3390/ph13100289.