ADC ID	DRG0YZEVV
ADC Name	MT-5111
Synonyms	MT 5111; MT-5111; MT5111    Click to Show/Hide
Organization	Molecular Templates, Inc.
Drug Status	Phase 1 (discontinued)
Antibody Name	Undisclosed
Antigen Name	Receptor tyrosine-protein kinase erbB-2 (ERBB2)					Antigen Info
Payload Name	Shiga toxin B subunit (StxB)					Payload Info
Therapeutic Target	Ribosome (RB)					Target Info
Linker Name	Undisclosed

Standard Type	Value	Units	Description	Reference
Maximum Observed Concentration (Cmax)	33	ng/mL	A phase 1 study of the novel immunotoxin MT-5111 in patients with HER2+ tumors: interim results, 6.75 ug/kg, N=5	[2]
Maximum Observed Concentration (Cmax)	0.6	nM	A phase 1 study of the novel immunotoxin MT-5111 in patients with HER2+ tumors: interim results, 6.75 ug/kg, N=5	[2]
Maximum Observed Concentration (Cmax)	54	ng/mL	A phase 1 study of the novel immunotoxin MT-5111 in patients with HER2+ tumors: interim results, 10 ug/kg, N=11	[2]
Maximum Observed Concentration (Cmax)	0.98	nM	A phase 1 study of the novel immunotoxin MT-5111 in patients with HER2+ tumors: interim results, 10 ug/kg, N=11	[2]
Maximum Observed Concentration (Cmax)	81	ng/mL	A phase 1 study of the novel immunotoxin MT-5111 in patients with HER2+ tumors: interim results, 13 ug/kg, N=3	[2]
Maximum Observed Concentration (Cmax)	1.47	nM	A phase 1 study of the novel immunotoxin MT-5111 in patients with HER2+ tumors: interim results, 13 ug/kg, N=3	[2]
Maximum Observed Concentration (Cmax)	93	ng/mL	A phase 1 study of the novel immunotoxin MT-5111 in patients with HER2+ tumors: interim results, 17 ug/kg, N=4	[2]
Maximum Observed Concentration (Cmax)	1.69	nM	A phase 1 study of the novel immunotoxin MT-5111 in patients with HER2+ tumors: interim results, 17 ug/kg, N=4	[2]

Standard Type	Value	Units	Description	Reference
Elimination Half-Life (t1/2)	2-5	h	MT-5111 was designed to achieve a short half-life to allow for efficient tumor cell targeting but minimal serum exposure time to avoid systemic effects over time. This short half-life was confirmed in primates    Click to Show/Hide	[1]
Elimination Half-Life (t1/2)	3.9	h	A phase 1 study of the novel immunotoxin MT-5111 in patients with HER2+ tumors: interim results, 6.75 ug/kg, N=5	[2]
Elimination Half-Life (t1/2)	6.9	h	A phase 1 study of the novel immunotoxin MT-5111 in patients with HER2+ tumors: interim results, 10 ug/kg, N=11	[2]
Elimination Half-Life (t1/2)	5.3	h	A phase 1 study of the novel immunotoxin MT-5111 in patients with HER2+ tumors: interim results, 13 ug/kg, N=3	[2]
Elimination Half-Life (t1/2)	6.6	h	A phase 1 study of the novel immunotoxin MT-5111 in patients with HER2+ tumors: interim results, 17 ug/kg, N=4	[2]

Standard Type	NCT Number	Clinical Status	Clinical Trial Description
Undisclosed	NCT04029922	PHASE1	A Phase 1 Open-label, Multicenter Dose Escalation and Expansion Study of MT-5111 in Subjects With Previously Treated Advanced HER2-positive Solid Tumors
Undisclosed	NCT04757090	PHASE2	A Pilot Study of 89Zr-Trastuzumab PET/CT in Subjects With Previously Treated HER2-Positive Solid Tumors Scheduled to Receive Treatment With MT-5111

Experiment 1 Reporting the Activity Date of This ADC					[3]
Patients Enrolled	Eligible patients have HER2-positive unresectable/metastatic solid tumors (Part A: all types; Part B: breast/GEA) refractory to prior therapies, measurable/evaluable lesions (RECIST 1.1), ECOG ≤1, and adequate organ function. Exclusions include active CNS metastases, uncontrolled comorbidities, significant cardiovascular disease, or concurrent infections (HBV/HCV/HIV).    Click to Show/Hide
Administration Dosage	The assigned dose level of MT-5111 will be given as an intravenous (IV) infusion over about 30 minutes on the same day every week (i.e., on day 1, day 8 and day 15 of each cycle).
Related Clinical Trial
NCT Number	NCT04029922	Clinical Status	PHASE1
Clinical Description	A Phase 1 Open-label, Multicenter Dose Escalation and Expansion Study of MT-5111 in Subjects With Previously Treated Advanced HER2-positive Solid Tumors
Primary Endpoint	The primary objectives are to assess the safety and tolerability of MT-5111 by monitoring adverse events (CTCAE v5.0) and dose-limiting toxicities (DLTs) to determine the MTD/RP2D over 21-day cycles.
Other Endpoint	Secondary objectives include evaluating MT-5111 pharmacokinetics (Cmax, Tmax, AUC) on Days 1/8/15 per cycle, tumor response (ORR per RECIST 1.1), and immunogenicity (ADA/NAb titers) at baseline, treatment cycles, and follow-up.
Experiment 2 Reporting the Activity Date of This ADC					[4]
Patients Enrolled	Eligible participants must be enrolled in MT-5111_001 with ≥1 measurable lesion (RECIST 1.1; osteosarcoma exceptions permitted), have recent/planned FDG-PET/CT, and be capable of PET/CT imaging. Exclusions include hepatic-only disease and pregnancy/breastfeeding status.
Administration Dosage	.
Related Clinical Trial
NCT Number	NCT04757090	Clinical Status	PHASE2
Clinical Description	A Pilot Study of 89Zr-Trastuzumab PET/CT in Subjects With Previously Treated HER2-Positive Solid Tumors Scheduled to Receive Treatment With MT-5111
Primary Endpoint	The primary imaging endpoint is the average 89Zr-trastuzumab SUVmax (maximum standardized uptake value) in lesions identified on baseline FDG-PET/CT scans.
Other Endpoint	Secondary imaging analyses include average 89Zr-trastuzumab tumor-to-normal tissue and tumor-to-blood uptake ratios, along with intra-patient heterogeneity assessment (fractions of scan-positive/negative lesions) in multi-lesion cases.

Ref 1	Abstract P1-18-35: MT-5111, a novel HER2 targeting engineered toxin body, under clinical development to overcome mechanisms of resistance to existing HER2 targeted therapies
Ref 2	Abstract OT2-11-01: A phase 1 study of the novel immunotoxin MT-5111 in patients with HER2+ tumors: interim results
Ref 3	Study of MT-5111 in HER2-positive Solid Tumors
Ref 4	89Zr-Trastuzumab PET/CT in Subjects With Previously Treated HER2-Positive Solid Tumors Scheduled to Receive Treatment With MT-5111