Rovalpituzumab tesirine

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]

Rovalpituzumab tesirine
Monoclonal antibody
TypeWhole antibody
SourceHumanized
TargetDLL3
Clinical data
ATC code
  • None
Identifiers
CAS Number
ChemSpider
  • none
UNII
KEGG
Chemical and physical data
FormulaC6416H9894N1698O2028S46 (non-glycosylated)

Development

In 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

Chemical 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

References
  1. "Statement On A Nonproprietary Name Adopted By The USAN Council: USAN (de-144) Rovalpituzumab" (PDF). Searchusan.ama-assn.org. Retrieved 2017-05-23.
  2. 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.
  3. "Rova-T (Rovalpituzumab tesirine)". BioCentury.
  4. "AbbVie Discontinues Rovalpituzumab Tesirine (Rova-T) Research and Development Program | AbbVie News Center". news.abbvie.com. Retrieved 29 August 2019.
  5. 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)
  6. "It's official—AbbVie dumps Rova-T after another lung cancer fail". FierceBiotech. Retrieved 29 August 2019.
  7. 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
  8. "AbbVie ditches plans for accelerated Rova-T review after weak phase 2 data". FierceBiotech. Retrieved 29 August 2019.
  9. "International Nonproprietary Names for Pharmaceutical Substances (INN). Recommended INN: List 75" (PDF). WHO Drug Information. World Health Organization. 30 (1): 151. 2016.
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