Rovalpituzumab tesirine (Rova-T) is an experimental antibody-drug conjugate targeting the protein

DLL3 Delta-like 3 (Drosophila), also known as DLL3, is a protein which in humans is encoded by the ''DLL3'' gene. Two transcript variants encoding distinct isoforms have been identified for this gene. Function This gene encodes a member of the delt ...

on tumor cells. It was originally developed by Stemcentrx and was purchased by

AbbVie AbbVie Inc. is an American pharmaceutical company headquartered in North Chicago, Illinois. It is ranked sixth on the list of largest biomedical companies by revenue. In 2023, the company's seat in Forbes Global 2000 was 74, and rank 89 on the ...

. It was tested for use in

small-cell lung cancer Small-cell carcinoma, also known as oat cell carcinoma, is a type of highly malignant cancer that most commonly arises within the lung, although it can occasionally arise in other body sites, such as the cervix, prostate, and gastrointestinal tr ...

, but development was terminated after unsuccessful

phase III trial The phases of clinical research are the stages in which scientists conduct experiments with a health intervention to obtain sufficient evidence for a process considered effective as a medical treatment. For drug development, the clinical phases ...

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. 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%.

Chemical structure

Chemical structure of "tesirine" (drawn in black). It consists of a pyrrolobenzodiazepine type

dimer Dimer may refer to: * Dimer (chemistry), a chemical structure formed from two similar sub-units ** Protein dimer, a protein quaternary structure ** d-dimer ** TH-dimer * Dimer model, an item in statistical mechanics, based on ''domino tiling'' * ...

(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 Polyethylene glycol (PEG; ) is a polyether compound derived from petroleum with many applications, from industrial manufacturing to medicine. PEG is also known as polyethylene oxide (PEO) or polyoxyethylene (POE), depending on its molecular wei ...

spacer, and a

maleimide Maleimide is a chemical compound with the formula H2C2(CO)2NH (see diagram). This unsaturated imide is an important building block in organic synthesis. The name is a contraction of maleic acid and imide, the -C(O)NHC(O)- functional group. Malei ...

linker which is attached to a

cysteine Cysteine (; symbol Cys or C) is a semiessential proteinogenic amino acid with the chemical formula, formula . The thiol side chain in cysteine enables the formation of Disulfide, disulfide bonds, and often participates in enzymatic reactions as ...

in the antibody's (rovalpituzumab's)

peptide Peptides are short chains of amino acids linked by peptide bonds. A polypeptide is a longer, continuous, unbranched peptide chain. Polypeptides that have a molecular mass of 10,000 Da or more are called proteins. Chains of fewer than twenty am ...

backbone, drawn blue. Each rovalpituzumab molecule has an average of two such attachments.

References

{{monoclonals for tumors Experimental cancer drugs Antibody-drug conjugates Orphan drugs Monoclonal antibodies for tumors

Development

Chemical structure

See also

References