Rovalpituzumab tesirine (Rova-T) is an experimental antibody-drug conjugate targeting the protein DLL3 on tumor cells.[1][2] It was originally developed by Stemcentrx and was purchased by AbbVie.[3] It was tested for use in small-cell lung cancer, but development was terminated after unsuccessful phase III trial.[4][5]
| Monoclonal antibody | |
|---|---|
| Type | Whole antibody |
| Source | Humanized |
| Target | DLL3 |
| Clinical data | |
| ATC code |
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| Identifiers | |
| CAS Number | |
| ChemSpider |
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| UNII | |
| KEGG | |
| Chemical and physical data | |
| Formula | C6416H9894N1698O2028S46 (non-glycosylated) |
Development
editIn 2018, an Independent Data Monitoring Committee found that in the TAHOE phase III trial, Rova-T shortened survival of lung cancer patients compared to SOC chemotherapy topotecan, prompting termination of trial enrollment. Another phase III trial (MERU) demonstrated no survival benefit over placebo.[6][7] A phase II trial using the drug as a third-line treatment for relapsed or refractory lung cancer showed objective response rate at just 16%.[8]
Chemical structure
editChemical structure of "tesirine" (drawn in black). It consists of a pyrrolobenzodiazepine type dimer (top), which is the actual anti-cancer agent, a Val–Ala structure that can be cleaved by an enzyme to detach the anti-cancer agent from the antibody, a polyethylene glycol spacer, and a maleimide linker which is attached to a cysteine in the antibody's (rovalpituzumab's) peptide backbone, drawn blue. Each rovalpituzumab molecule has an average of two such attachments.[9]
See also
edit- Vadastuximab talirine, with a similar cytotoxin
References
edit- ^ "Statement On A Nonproprietary Name Adopted By The USAN Council: USAN (de-144) Rovalpituzumab" (PDF). Searchusan.ama-assn.org. Retrieved 2017-05-23.
- ^ Lashari BH, Vallatharasu Y, Kolandra L, Hamid M, Uprety D (December 2018). "Rovalpituzumab Tesirine: A Novel DLL3-Targeting Antibody-Drug Conjugate". Drugs in R&D. 18 (4): 255–258. doi:10.1007/s40268-018-0247-7. PMC 6277321. PMID 30232719.
- ^ "Rova-T (Rovalpituzumab tesirine)". BioCentury.
- ^ "AbbVie Discontinues Rovalpituzumab Tesirine (Rova-T) Research and Development Program | AbbVie News Center". news.abbvie.com. Retrieved 29 August 2019.
- ^ Alternative Names: Rova-T; SC16LD6.5. "Rovalpituzumab tesirine - AdisInsight". Adisinsight.springer.com. Retrieved 2017-05-22.
{{cite web}}: CS1 maint: multiple names: authors list (link) CS1 maint: numeric names: authors list (link) - ^ "It's official—AbbVie dumps Rova-T after another lung cancer fail". FierceBiotech. Retrieved 29 August 2019.
- ^ Clinical trial number NCT03033511 for "A Study of Rovalpituzumab Tesirine as Maintenance Therapy Following First-Line Platinum-Based Chemotherapy in Participants With Extensive Stage Small Cell Lung Cancer (MERU) " at ClinicalTrials.gov
- ^ "AbbVie ditches plans for accelerated Rova-T review after weak phase 2 data". FierceBiotech. Retrieved 29 August 2019.
- ^ "International Nonproprietary Names for Pharmaceutical Substances (INN). Recommended INN: List 75" (PDF). WHO Drug Information. 30 (1). World Health Organization: 151. 2016.