Glembatumumab vedotin
Monoclonal antibody | |
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Type | Whole antibody |
Source | Human |
Target | GPNMB |
Clinical data | |
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Glembatumumab vedotin (also known as CDX-011 and CR011-vcMMAE) is an
In May 2010, the U.S
Structure and mechanism
The fully human
It uses a valine-citrulline enzyme-cleavable linker.[2] The linkage is stable in the bloodstream. The antibody binds to GPNMB on the cancer cells, the ADC is internalised, the linkage is broken and MMAE is released to kill the cell.[3]
In preclinical studies glembatumumab vedotin was capable of killing GPNMB expressing melanoma and breast cancer cells in vitro[4][5] and inducing partial or complete regression of GPNMB-expressing tumors in mouse models.[3][5][6]
Development
Glembatumumab vedotin was in development through April 2018 by
Clinical trials
In September 2010 a Phase 2b clinical study started of glembatumumab vedotin in 120 patients with GPNMB-expressing breast cancer including those with
As of June 2011[update], Phase I/II clinical trials of glembatumumab vedotin for the treatment of advanced melanoma[9] and breast cancer[10] have been completed but no official study result was posted. Preliminary results from these trials have shown that glembatumumab vedotin has some clinical activity (promotes tumor shrinkage) in both cancer types.[11] Patients whose tumors express GPNMB respond better to glembatumumab and have longer progression-free survival than those whose tumors do not express GPNMB; in melanoma,[12] and breast cancer.[13]
An
Development of the ADC was discontinued in April 2018 after missing the primary endpoint of its study and failed to help women with tough-to-treat metastatic triple-negative breast cancers (TNBC) stay both alive and progression-free for longer than Roche Holding AG's Xeloda (capecitabine).[7]
References
- ^ "Celldex Therapeutics Announces Initiation Of Randomized Phase 2b Clinical Trial Of CDX-011 In Advanced Breast Cancer". 22 Sep 2010. Archived from the original on 4 November 2010. Retrieved 8 November 2010.
- PMID 25267741.
- ^ a b "CuraGen Announces Expansion Of CR011-vcMMAE Phase II Trial In Advanced Breast Cancer". 18 June 2009. Archived from the original on 20 June 2009. Retrieved 28 August 2010.
- PMID 19383330.
- ^ PMID 20215530.
- PMID 16489096.
- ^ a b "Celldex TNBC trial failure dashes company's plans". BioWorld. Archived from the original on 2018-06-18. Retrieved 2018-04-17.
- ^ "Glembatumumab vedotin - Celldex Therapeutics Inc - AdisInsight".
- ^ Clinical trial number NCT00412828 for "A Phase I/II Study of CR011-vcMMAE in Subjects With Unresectable Stage III or Stage IV Melanoma" at ClinicalTrials.gov
- ^ Clinical trial number NCT00704158 for "Study of CR011-vcMMAE to Treat Locally Advanced or Metastatic Breast Cancer" at ClinicalTrials.gov
- ^ "Celldex: Scientific Articles". Archived from the original on 2013-07-02. Retrieved 2010-11-08.
- .
- ^ "Celldex Therapeutics Presents Positive Results From Phase 2 Study Of The Antibody-Drug Conjugate Product Candidate CDX-011 In Advanced Breast Cancer". MedicalNewsToday. 19 December 2009.
- ^ Clinical trial number NCT01997333 for "Study of Glembatumumab Vedotin (CDX-011) in Patients With Metastatic, gpNMB Over-Expressing, Triple Negative Breast Cancer (METRIC)" at ClinicalTrials.gov
- World Health Organization (2009). "International Nonproprietary Names for Pharmaceutical Substances (INN). Proposed INN: List 102" (PDF). WHO Drug Information. 23 (4): 330.