Evidence map›Paper›PMID 39829185›Full record

ArticleBioanalysis2025

The validation and clinical bioanalysis of the Bicycle® Toxin Conjugate zelenectide pevedotin in human plasma.

Joseph A Tweed, Fern Adams-Dam, Justin Bader, Ying Zhang, Jane Allanson, Kevin Holmes, Ryan Senior, Mike Rigby, Phil Jeffrey, Hongmei Xu

Registry-linked trialAbstract readValidation Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Bioanalysis, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04561362 (Phase I/II Study of the Safety, Pharmacokinetics, and Preliminary Clinical Activity of BT8009 in Patients With Nectin-4 Expressing Advanced Malignancies), which is not on this map. Not yet cited in PubMed.

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0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT04561362 phase1 / phase2active not recruitingnot on this map

Phase I/II Study of the Safety, Pharmacokinetics, and Preliminary Clinical Activity of BT8009 in Patients With Nectin-4 Expressing Advanced Malignancies

TypeinterventionalSponsorBicycleTx LimitedRan2020 to 2026Enrolled329ConditionsUrinary Bladder Neoplasm, Triple Negative Breast Neoplasms, Hormone Receptor Positive, HER2-negative Neoplasms, Hormone Receptor Positive, HER2-low NeoplasmsArmsBT8009, Pembrolizumab
3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Joseph A TweedQuantitative Pharmacology, Bicycle Therapeutics, Cambridge, MA, USA.
Fern Adams-DamYork Bioanalytical Solutions Limited, York, UK.
Justin BaderQuantitative Pharmacology, Bicycle Therapeutics, Cambridge, MA, USA.
Ying ZhangQuantitative Pharmacology, Bicycle Therapeutics, Cambridge, MA, USA.
Jane AllansonYork Bioanalytical Solutions Limited, York, UK.
Kevin HolmesYork Bioanalytical Solutions Limited, York, UK.
Ryan SeniorYork Bioanalytical Solutions Limited, York, UK.
Mike RigbyTherapeutics, Bicycle Therapeutics, Cambridge, UK.
Phil JeffreyPreclinical Development, Bicycle Therapeutics, Cambridge, UK.
Hongmei XuQuantitative Pharmacology, Bicycle Therapeutics, Cambridge, MA, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe Bicycle® toxin conjugate (BTC) zelenectide pevedotin, formerly known as BT8009, is a novel bicyclic peptide targeting the Nectin-4 tumor antigen conjugated to the cytotoxin monomethyl auristatin E (MMAE) via a valine-citrulline cleavable linker. Zelenectide pevedotin is currently being investigated in a Phase 1/2 (Duravelo-1, NCT04561362) clinical trial to determine safety and efficacy in patients with tumors associated with Nectin-4 expression. A simple regulated bioanalytical assay was developed to quantify intact zelenectide pevedotin in patient plasma samples. METHODOLOGY: Quantitation of the intact zelenectide pevedotin and its analog internal standard BCY6063 encompassed a routine protein precipitation procedure followed by reverse phase chromatographic separation paired with tandem mass spectrometric detection.

resultsIntact zelenectide pevedotin was quantified over the assay range of 5-2500 ng/mL using 50 µL of human plasma. The method was validated according to local standard operating procedures and has met all US Food and Drug Administration and European Medicines Agency regulatory guidance criteria.

conclusionA bioanalytical method for measuring zelenectide pevedotin in plasma samples was developed and successfully applied in evaluating over 3000 samples from patients in a Phase 1/2 clinical study of zelenectide pevedotin in patients with advanced solid tumors.

Indexed as

Chromatography, Reverse-PhaseHumansTandem Mass SpectrometryBicycle® Toxin ConjugatebioanalysisBT8009cyclic peptideMMAEpeptide drug conjugateZelenectide pevedotin

Identifiers

PMID39829185
PMCPMC11853612

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.