Evidence map›Paper›PMID 39690276›Full record

ArticleJournal of pharmacokinetics and pharmacodynamics2024

QSP modeling of a transiently inactivating antibody-drug conjugate highlights benefit of short antibody half life.

Eshita Khera, Lekshmi Dharmarajan, Dominik Hainzl, Volker Engelhardt, Helena Vostiarova, John Davis, Nicolas Ebel, Kuno Wuersch, Vincent Romanet, Sherif Sharaby and 1 more

Abstract read
In one paragraph

Article in Journal of pharmacokinetics and pharmacodynamics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Review
  2. Review
  3. Article
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

11 authors.

Eshita Khera *PK Sciences, Translational Medicine, Novartis Biomedical Research, Cambridge, MA, USA.ORCID 0000-0002-6971-1033
Lekshmi Dharmarajan *PK Sciences, Translational Medicine, Novartis Biomedical Research, Basel, Switzerland.
Dominik HainzlPK Sciences, Translational Medicine, Novartis Biomedical Research, Cambridge, MA, USA.
Volker EngelhardtPK Sciences, Translational Medicine, Novartis Biomedical Research, Basel, Switzerland.
Helena VostiarovaPK Sciences, Translational Medicine, Novartis Biomedical Research, Basel, Switzerland.
John DavisPK Sciences, Translational Medicine, Novartis Biomedical Research, Cambridge, MA, USA.
Nicolas EbelOncology, Novartis Biomedical Research, Basel, Switzerland.
Kuno WuerschPreclinical Safety, Novartis Biomedical Research, Basel, Switzerland.
Vincent RomanetOncology, Novartis Biomedical Research, Basel, Switzerland.
Sherif SharabyPK Sciences, Translational Medicine, Novartis Biomedical Research, East Hanover, NJ, USA.ORCID 0009-0003-6259-4369
Jeffrey D KearnsPK Sciences, Translational Medicine, Novartis Biomedical Research, Cambridge, MA, USA. jeff.kearns@novartis.com.ORCID 0000-0001-7261-5096

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Antibody drug conjugates (ADC) are a promising class of oncology therapeutics consisting of an antibody conjugated to a payload via a linker. DYP688 is a novel ADC comprising of a signaling protein inhibitor payload (FR900359) that undergoes unique on-antibody inactivation in plasma, resulting in complex pharmacology. To assess the impact of FR inactivation on DYP688 pharmacology and clinical developability, we performed translational modeling of preclinical PK and tumor growth inhibition (TGI) data, accompanied by mechanistic Krogh cylinder tumor modeling. Using a PK-TGI model, we identified a composite exposure-above-tumorostatic concentration (AUC

Indexed as

ImmunoconjugatesAnimalsAntineoplastic AgentsCell Line, TumorHalf-LifeHumansMiceModels, BiologicalNeoplasmsNetwork PharmacologyXenograft Model Antitumor AssaysAntineoplastic AgentsImmunoconjugatesAntibody-drug conjugateAntibody half-lifeLinker-payload metabolismPredictive modelingQuantitative systems pharmacology

Identifiers

PMID39690276
PMCPMC11652588

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

None linked

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.