Tobemstomig Clinical Bispecific

Antibody Information

Entry ID	1214
INN	Tobemstomig
Status	Clinical
Drug code(s)	RO7247669, RG6139
Brand name	None
mAb sequence source	mAb humanized
General Molecular Category	Bispecific
Format, general category	Full length Ab
Format details	1+1 CrossMab
Isotype (Fc)	IgG1
Light chain isotype	kappa
Linker	None
Ave. DAR	None
Conjugated/fused moiety	None
Discovery method/technology	None

Therapeutic information

Target(s)	LAG-3, PD-1
Indications of clinical studies	Liver cancer, Breast cancer, renal cell carcinoma, Non-small cell lung cancer, Urothelial cancer, Melanoma, Squamous Cell Carcinoma of the Esophagus, 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)	Phase 2
Status	Active
Start of clinical phase (IND filing or first Phase 1)	October 15, 2019
Start of Phase 2	June 25, 2021
Start of Phase 3
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	Hoffmann-La Roche
Licensee/Partner	None
Comments about company or candidate	Mar 2025: Two Phase 1/2 studies in liver cancer are recruiting patients (NCT05908786, NCT04524871); all other studies are completed or active not recruiting. Oct 23, 2024 pipeline update: Listed as removed from pipeline for solid tumors. NCT05805501 Phase 2 in renal cell carcinoma started in Mar 2023. NCT05775289 Phase 2 in NSCLC started in Mar 2023. NCT04785820 is a 3-Arm, Randomized, Blinded, Active-Controlled, Phase II Study of RO7121661, a PD1-TIM3 Bispecific Antibody and RO7247669, a PD1-LAG3 Bispecific Antibody, Compared With Nivolumab in Participants With Advanced or Metastatic Squamous Cell Carcinoma of the Esophagus started in June 2021. NCT04140500 Phase 1 first-in-human study in solid tumors started Nov 11. 2019. Listed as advanced to Phase 1 in pipeline update dated Jan 30, 2020.
Full address of company	Basel, Switzerland Europe Switzerland https://www.roche.com/about

Description/comment

Immune checkpoint modulatory. The bispecific monoclonal antibody PD1 x LAG3 (RG6139) binds to the PD-1 and LAG-3 inhibitory checkpoint receptors on the surface of T-cells. PD1 x LAG3 MAb enable preferential targeting of dysfunctional effector T-cells over regulatory T-cells mediating immunosuppressive effects while restoring anti-tumor immune response. RG6139 is currently in phase I clinical study for solid tumors.
Fc silent (LALAPG-Fc); not internalized by activated T cells, not removed from cell surface by macrophages (so called drug shaving observed with nivolumab)

Additional information

Anticipated events	None
Factor(s) contributing to discontinuation	None