Dalotuzumab Terminated Naked monospecific

Antibody Information

Entry ID	2308
INN	Dalotuzumab
Status	Terminated
Drug code(s)	MK-0646, F50035, h7C10
Brand name	None
mAb sequence source	mAb humanized
General Molecular Category	Naked monospecific
Format, general category	Full length Ab
Format details	None
Isotype (Fc)	IgG1
Light chain isotype	kappa
Linker	None
Ave. DAR	None
Conjugated/fused moiety	None
Discovery method/technology	None

Therapeutic information

Target(s)	IGF-1R
Indications of clinical studies	Breast Cancer, Colorectal Cancer, Non-small-cell Lung cancer, Neuroendocrine Tumors, Pancreatic Cancer, Solid Tumor, Multiple Myeloma
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)	Terminated at Phase 2/3
Status	Inactive
Start of clinical phase (IND filing or first Phase 1)	December 15, 2005
Start of Phase 2	June 15, 2007
Start of Phase 3	December 15, 2007
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	Merck
Comments about company or candidate	One Phase 2 study active but not recruiting as of Aug 2017. Total of 20 studies sponsored at least in part by Merck listed on clinicaltrials.gov. Phase 2/3 study done in colorectal patients; results showed that the trial was stopped at the 1st interim analysis with 345 wild-type KRAS patients enrolled as neither dalotuzumab dosing regimen achieved proof-of-concept. Median PFS for all randomized wild-type KRAS status patients was 3.3mth in q 1wk and 5.4 in q 2wk vs 5.6 in the placebo group. Median overall survival (OS) for wild-type KRAS patients was 10.8mth in q 1wk and 11.6 in q 2wk vs 14.0 in the placebo arm. Specific adverse events did not appear to explain the difference in PFS or OS observed. Poor results also observed in Phase 2 studies in breast cancer and prostate cancer.
Full address of company	Castres, 1 Avenue d'Albi, France Europe France https://www.pierre-fabre.com/fr-fr

Description/comment

Jan 2005 publication from Pierre Fabre authors: We have generated a humanized anti-IGF-IR antibody h7C10 that blocks in vitro IGF-I and IGF-II-induced cell proliferation of MCF-7 breast cancer cells. Analysis of the IGF-I transduction cascade demonstrated that the humanized anti-IGF-IR antibody and its murine parental form block IGF-I-induced tyrosine phosphorylation, both its beta-chain and IRS-1 tyrosine phosphorylation. https://pubmed.ncbi.nlm.nih.gov/15386423/

Additional information

Anticipated events	None
Factor(s) contributing to discontinuation	Lack of efficacy