Evidence map›Paper›PMID 35191618›Full record

Trial reportCPT: pharmacometrics & systems pharmacology2022

Covariate analysis of tusamitamab ravtansine, a DM4 anti-CEACAM5 antibody-drug conjugate, based on first-in-human study.

Clemence Pouzin, Michel Tod, Mustapha Chadjaa, Nathalie Fagniez, Laurent Nguyen

Open access · goldAbstract readClinical Trial, Phase IClinical Trial, Phase II
In one paragraph

Trial report in CPT: pharmacometrics & systems pharmacology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.4field-weighted citation impact, top 20% of its field
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

6 citing papers in PubMed, 11 citations in OpenAlex.

  1. Trial
  2. Trial
  3. Article
  4. Review
  5. Review
  6. 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

5 authors at 2 institutions in 1 country.

Clemence PouzinPharmacokinetics Dynamics and Metabolism Department, Sanofi R&D, Paris, France.
Michel TodPKPD Modelling Unit, Oncology Department EMR3738, University of Claude Bernard Lyon 1, Lyon, France.
Mustapha ChadjaaClinical Research, Sanofi R&D, Paris, France.
Nathalie FagniezPharmacokinetics Dynamics and Metabolism Department, Sanofi R&D, Paris, France.
Laurent NguyenPharmacokinetics Dynamics and Metabolism Department, Sanofi R&D, Paris, France.
Sanofi (France) · FRUniversité Claude Bernard Lyon 1 · FR

Funding

Sanofi R&D
6 · The paper itself

Abstract

Tusamitamab ravtansine is an anti-CEACAM5 antibody-drug conjugate indicated in patients with solid tumors. Based on a previous developed semimechanistic model describing simultaneously pharmacokinetic (PK) of SAR408701, two of its active metabolites: DM4 and methyl-DM4 and naked antibody, with integration of drug-to-antibody data, the main objective of the present analysis was to evaluate covariate's impact in patients from phase I/II study (n = 254). Demographic and pathophysiologic baseline covariates were explored to explain interindividual variability on each entity PK parameter. Model parameters were estimated with good precision. Five covariates were included in the final PK model: body surface area (BSA), tumor burden, albumin, circulating target, and gender. Comparison of BSA-adjusted dosing and flat dosing supported the current BSA-based dosing regimen, to limit under and over exposure in patients with extreme BSA. Overall, this model characterized accurately the PKs of all entities and highlighted sources of PK variability. By integrating mechanistic considerations, this model aimed to improve understanding of the SAR408701 complex disposition while supporting key steps of clinical development.

Indexed as

Antineoplastic AgentsImmunoconjugatesMaytansineNeoplasmsAntibodies, MonoclonalHumansAntibodies, MonoclonalAntineoplastic AgentsImmunoconjugatesMaytansine

Identifiers

PMID35191618
PMCPMC8923727
OpenAlexW4213368743

What OpenQuestion holds

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LicenceCC BY-NC-ND
Read underepoch 390

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.