Zilovertamab vedotin Clinical ADC

Antibody Information

Entry ID	1428
INN	Zilovertamab vedotin
Status	Clinical
Drug code(s)	VLS-101, MK-2140
Brand name	None
mAb sequence source	mAb humanized
General Molecular Category	ADC
Format, general category	Full length Ab conjugate
Format details	None
Isotype (Fc)	IgG1
Light chain isotype	kappa
Linker	Valine-citrulline (Maleimidocaproyl-valine-citrulline-para-aminobenzoate; Cleavable linker)
Ave. DAR	4
Conjugated/fused moiety	Tubulin inhibitor, Monomethyl auristatin E (MMAE)
Discovery method/technology	None

Therapeutic information

Target(s)	ROR1
Indications of clinical studies	Diffuse Large B-Cell Lymphoma, Solid tumors, Hematological malignancies
Primary therapeutic area	Cancer

Development stage information

Phase lengths*

*The graph represents early-stage clinical development phase lengths. For molecules approved or under evaluation for marketing authorization in the US is provided a complete overview of all clinical development phase lengths. Phase lengths are calculated from the start of the first in human (FIH) study (Start of clinical phase). “Start of Phase 2” bar represents Phase 1 length (Start of clinical phase to start of Phase 2); “Start of Phase 3” bar represents Phase 1+2 length (Start of clinical phase to start of Phase 3); “Date BLA/NDA submitted” bar represents Phase 1+2+3 length (Start of clinical phase to Date BLA/NDA submitted); and “Date of first US approval” bar represents Phase 1 to first US approval length (Start of clinical phase to Date of first US approval).

Most advanced stage of development (global)	Phase 3
Status	Active
Start of clinical phase (IND filing or first Phase 1)	February 01, 2019
Start of Phase 2	October 19, 2020
Start of Phase 3	January 15, 2022
Date BLA/NDA submitted to FDA
Year of first approval (global)	None
Date of first US approval
INN, US product name	None
US or EU approved indications	None

Company information

Company	Merck Sharp & Dohme LLC
Licensee/Partner	None
Comments about company or candidate	NCT06717347 Phase 3 in DLBCL started in Dec 2024. NCT06395103 Phase 2 started in Aug 2024. NCT05139017 Phase 2/3 in Diffuse Large B-Cell Lymphoma started in Jan 2022 recruiting as of last update in May 2023. Merck Sharp & Dohme LLC acquired VelosBio Inc. Oct 19, 2020: Biopharmaceutical company VelosBio has dosed the first patient in a Phase II trial of investigational drug VLS-101 in patients with solid tumours. Aug 31, 2020: The FDA has granted a Fast Track and Orphan Drug designation to VLS-101, a novel first-in-class antibody-drug conjugate targeting receptor tyrosine kinase-like orphan receptor 1 (ROR1), for the treatment of patients with mantle cell lymphoma NCT04504916 Phase 2 not yet recruiting when first posted on Aug 7 2020. NCT03833180 Phase 1 for Hematological Malignancies started in Feb 2019; results https://ash.confex.com/ash/2020/webprogram/Paper136373.html
Full address of company	Rahway, NJ 07065 USA North America United States of America https://www.merck.com/contact-us/

Description/comment

The anti-ROR1 antibody, UC-961, is ahumanized IgG1 monoclonal antibody (mAb) that binds with high affinity to a specific extracellular epitope of human ROR1 receptor and can block Wnt5a-induced ROR1 signaling. Nonclinical studies document that UC-961 does not react with normal adult human tissues and selectively binds to tumor cells. Because of the antibody high specificity, rapid internalization, and trafficking to lysosomes, UC-961 appears ideally suited to serve as the targeting moiety for an anti-ROR1 ADC. Accordingly, we have developed VLS-101, a UC-961-linker-monomethyl auristatin E (MMAE) ADC that preserves the high-affinity binding and specificity of UC-961 and allows for ROR1-targeted intracellular release of MMAE.

Additional information

Anticipated events	None
Factor(s) contributing to discontinuation	None