Telisotuzumab vedotin Regulatory review ADC

Antibody Information

Entry ID	199
INN	Telisotuzumab vedotin
Status	Regulatory review
Drug code(s)	ABBV-399
Brand name	(Pending)
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 (Cleavable linker)
Ave. DAR	3.1
Conjugated/fused moiety	Tubulin inhibitor, Monomethyl auristatin E (MMAE)
Discovery method/technology	None

Therapeutic information

Target(s)	cMET
Indications of clinical studies	Non-small cell lung cancer, advanced solid tumors
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)	Regulatory review US
Status	Active
Start of clinical phase (IND filing or first Phase 1)	March 15, 2014
Start of Phase 2	October 10, 2018
Start of Phase 3	March 25, 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	Pierre Fabre
Licensee/Partner	AbbVie
Comments about company or candidate	Sep 27, 2024: AbbVie announced submission of a Biologics License Application to the U.S. Food and Drug Administration for accelerated approval of telisotuzumab vedotin (Teliso-V) in adult patients with previously treated, locally advanced or metastatic epidermal growth factor receptor wild type, nonsquamous non-small cell lung cancer (NSCLC) with c-Met protein overexpression. NCT06093503 in NSCLC due to start in May 2024 was withdrawn due to strategic considerations. Phase 3 study for Non-small cell lung cancer (NCT04928846) started in Mar 2022 has primary completion date in Mar 2028. Jan 2021: AbbVie announced that the U.S. Food and Drug Administration (FDA) granted Breakthrough Therapy Designation (BTD) to investigational telisotuzumab vedotin (Teliso-V) for the treatment of patients with advanced/metastatic epidermal growth factor receptor (EGFR) wild type, nonsquamous non-small cell lung cancer (NSCLC) with high levels of c-Met overexpression whose disease has progressed on or after platinum-based therapy. NCT04928846 Phase 3 in NSCLC started in March 2022. NCT03539536 Phase 2 study in NSCLC still recruiting as of May 2021. May 2019: Results for Phase 2 NCT03574753 study presented at ASCO: ABBV-399 failed to meet the pre-specified response needed to justify continuing enrollment. Pneumonitis was an unanticipated toxicity observed in patients with SCC with previous immunotherapy exposure.Results of the phase 1b study of ABBV-399 presented at ASCO (https://ascopubs.org/doi/abs/10.1200/JCO.2019.37.15_suppl.3011). NCT03539536 Phase 2 in NSCLC started in Oct 2018; Phase 2 sponsored by Southwestern Oncology Group started in Feb 2018. Sep 2017: AbbVie and Bristol-Myers Squibb announced a clinical trial collaboration to evaluate the combination of AbbVie's investigational antibody drug conjugate ABBV-399 and Bristol-Myers Squibb's immunotherapy Opdivo (nivolumab) in c-Met overexpressing non-small cell lung cancer (NSCLC). NCT02099058 recruiting as of Aug 2017; ABBV-399 is well tolerated at a dose of 2.7 mg/kg every 21 days and has demonstrated antitumor activity in patients with c-Met+ NSCLC both as monotherapy and in combination with erlotinib. Updated data of antitumor activity and safety of ABBV-399 as monotherapy and in combination with erlotinib in c-Met+ NSCLC patients will be presented (DOI: http://dx.doi.org/10.1016/j.jtho.2016.11.449). AbbVie has collaboration with Seattle Genetics
Full address of company	Paris, France Europe France https://www.pierre-fabre.com/en-us

Description/comment

ABBV-399 was generated with the c-Met targeting antibody, ABT-700. Wang et al. ABBV-399, a c-Met Antibody Drug Conjugate that Targets Both MET Amplified and c-Met Overexpressing Tumors, Irrespective of MET Pathway Dependence. DOI: 10.1158/1078-0432.CCR-16-1568.
ABBV-399 was generated from the conjugation of vc MMAE to interchain disulfide bonds in ABT-700 after mild reduction to the sulfhydryl group (25). The average drug:antibody ratio of ABBV-399 was approximately 3.1.
Antibody described in "A novel antagonist anti-cMet antibody with antitumor activities targeting both ligand-dependent and
ligand-independent c-Met receptors" (DOI: 10.1002/ijc.30174)

Additional information

Anticipated events	None
Factor(s) contributing to discontinuation	None