Evidence map›Paper›PMID 40970968›Full record

Trial reportCancer chemotherapy and pharmacology2025

Population pharmacokinetic analysis of fluorouracil and oxaliplatin in the absence or presence of zolbetuximab in locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma.

Akihiro Yamada, Jianning Yang, Peter L Bonate, Nakyo Heo, Srinivasu Poondru

Registry-linked trialAbstract readClinical Trial, Phase II
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Cancer chemotherapy and pharmacology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03505320 (A Phase 2 Study of Zolbetuximab), which is not on this map. Cited by 1 paper, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed, 1 pooled it
–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.

NCT03505320 phase2active not recruitingnot on this map

A Phase 2 Study of Zolbetuximab (IMAB362) as Monotherapy and in Combination With Chemotherapy and/or Immunotherapy in Subjects With Metastatic or Locally Advanced Unresectable Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma and Locoregional Gastric or GEJ Adenocarcinoma Whose Are Claudin (CLDN) 18.2 Positive

TypeinterventionalSponsorAstellas Pharma Global Development, Inc.Ran2018 to 2027Enrolled143ConditionsPharmacokinetics of Zolbetuximab, Gastric Cancer, Gastro-esophageal Junction (GEJ) Cancer, Pharmacokinetics of OxaliplatinArmszolbetuximab, oxaliplatin, leucovorin, fluorouracil, Pembrolizumab
3 · Its place in the literature

Who cites it

1 citing paper in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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.

Akihiro Yamada *Astellas Pharma, Inc., Tokyo, Japan. akihiro.yamada@astellas.com.ORCID http://orcid.org/0009-0005-7527-1897
Jianning Yang *Astellas Pharma Global Development, Inc., Northbrook, IL, USA.
Peter L BonateAstellas Pharma Global Development, Inc., Northbrook, IL, USA.
Nakyo HeoAstellas Pharma Global Development, Inc., Northbrook, IL, USA.
Srinivasu PoondruAstellas Pharma Global Development, Inc., Northbrook, IL, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeZolbetuximab, a monoclonal antibody targeting claudin 18.2 (CLDN18.2), is approved in combination with chemotherapy for human epidermal growth factor receptor 2 (HER2)-negative, CLDN18.2-positive, unresectable, advanced or recurrent gastric cancer (in Japan) and in combination with fluoropyrimidine- and platinum-containing chemotherapy for first-line locally advanced unresectable or metastatic HER2-negative, CLDN18.2-positive gastric or gastroesophageal junction (G/GEJ) adenocarcinoma (in geographies including but not limited to the US, Europe, and China). Noncompartmental analysis (NCA) was previously used to evaluate the effect of zolbetuximab on pharmacokinetics (PK) of 5-fluorouracil (5-FU) and oxaliplatin; however, limitations of NCA confounded the results. This study utilized population pharmacokinetic (PopPK) analysis to address these limitations.

methodsIn Cohort 2 of the phase 2 ILUSTRO study (NCT03505320), patients with locally advanced unresectable or metastatic HER2-negative, CLDN18.2-positive G/GEJ adenocarcinoma received zolbetuximab with modified folinic acid, 5-FU, and oxaliplatin. PopPK models were developed to evaluate the impact of zolbetuximab on PK of 5-FU and oxaliplatin (including simultaneous analysis of free and total platinum).

resultsPK of 5-FU was adequately described by a 1-compartment model with zero-order input and first-order elimination. PK of free and total platinum was simultaneously described by a 3-compartment model with zero-order input, first-order elimination, and time-dependent free fraction. No impact of zolbetuximab on 5-FU PK or on systemic clearance or free fraction of oxaliplatin in plasma was observed. The effect of zolbetuximab on oxaliplatin distribution volume (12.3% decrease) was statistically significant but not considered clinically relevant.

conclusionPopPK analysis suggests no effect of zolbetuximab on 5-FU or oxaliplatin PK.

Indexed as

AdenocarcinomaAntineoplastic Combined Chemotherapy ProtocolsEsophageal NeoplasmsEsophagogastric JunctionStomach NeoplasmsAdultAgedFemaleFluorouracilHumansMaleMiddle AgedModels, BiologicalOxaliplatinFluorouracilOxaliplatin5-FluorouracilGastric/gastroesophageal junction adenocarcinomaOxaliplatinPopulation pharmacokineticsZolbetuximab

Identifiers

PMID40970968
PMCPMC12449379

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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.