Evidence map›Paper›PMID 39520048›Full record

Trial reportBritish journal of clinical pharmacology2025

Population pharmacokinetics and exposure-response relationships of dostarlimab in primary advanced or recurrent endometrial cancer in part 1 of RUBY.

Mita Kuchimanchi, Trine Lembrecht Jørgensen, Eva Hanze, Thierry André, Angela Jain, Dominique Berton, Oskar Alskär, Oleksandr Zub, Ana Oaknin, Mark S Shahin and 11 more

2 registry-linked trialsAbstract readMulticenter StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in British journal of clinical pharmacology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this 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.

NCT02715284 phase1active not recruitingnot on this map

A Phase 1 Dose Escalation and Cohort Expansion Study of TSR-042, an Anti-PD-1 Monoclonal Antibody, in Patients With Advanced Solid Tumors

TypeinterventionalSponsorTesaro, Inc.Ran2016 to 2028Enrolled729ConditionsNeoplasmsArmsDostarlimab
NCT03981796 phase3active not recruitingnot on this map

A Phase 3, Randomized, Double-blind, Multicenter Study of Dostarlimab (TSR-042) Plus Carboplatin-paclitaxel Versus Placebo Plus Carboplatin-paclitaxel in Patients With Recurrent or Primary Advanced Endometrial Cancer (RUBY)

TypeinterventionalSponsorTesaro, Inc.Ran2019 to 2026Enrolled785ConditionsNeoplasmsArmsDostarlimab, Placebo matching dostarlimab, Carboplatin, Paclitaxel, Niraparib
3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Trial
  2. Trial
  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

21 authors.

Mita KuchimanchiGSK, Waltham, MA, USA.ORCID https://orcid.org/0000-0003-0349-7756
Trine Lembrecht JørgensenOdense University Hospital, Odense, Denmark.
Eva HanzeqPharmetra, Uppsala, Sweden.
Thierry AndréSaint-Antoine Hospital, INSERM, Unité Mixte de Recherche Scientifique 938, and SIRIC CURAMUS, Sorbonne University, Paris, France.
Angela JainFox Chase Cancer Center, Philadelphia, PA, USA.
Dominique BertonGINECO & Institut de Cancerologie de l'Ouest, Centre René Gauducheau, Saint-Herblain, France.
Oskar AlskärqPharmetra, Uppsala, Sweden.
Oleksandr ZubChernihiv Medical Center of Modern Oncology, Chernihiv Regional Council, Chernihiv, Ukraine.
Ana OakninVall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain.
Mark S ShahinHanjani Institute for Gynecologic Oncology Abington Hospital-Jefferson Health, Asplundh Cancer Pavilion, Sidney Kimmel Medical College of Thomas Jefferson University, Willow Grove, PA, USA.
Anthoula KoliadiUppsala University Hospital, Uppsala, Sweden.
Bhavana PothuriGOG Foundation and Departments of Obstetrics/Gynecology and Medicine, Division of Gynecologic Oncology, Laura & Isaac Perlmutter Cancer Center, NYU Langone Health, New York, NY, USA.
Tom KrivakDivision of Gynecologic Oncology, The Western Pennsylvania Hospital, Pittsburgh, PA, USA.
Mikalai PishchykGrodno Regional Clinical Hospital, Grodno, Belarus.
Yakir SegevCarmel Medical Center, Technion-Israel Institute of Technology, Haifa, Israel.
Floor J BackesThe Ohio State University College of Medicine, The James Cancer Hospital and Solove Research Institute, Columbus, OH, USA.
Christine GennigensDepartment of Medical Oncology, CHU of Liège, Liège, Belgium.
Sara BouberhanMassachusetts General Hospital, Boston, MA, USA.
Stefan ZajicGSK, Collegeville, PA, USA.
Murad MelhemGSK, Waltham, MA, USA.
Joseph BuscemaArizona Oncology, Tucson, AZ, USA.

Funding

GSK, Waltham, MA, USA
6 · The paper itself

Abstract

aimsDostarlimab-gxly is a humanized monoclonal antibody of the IgG4 isotype that binds to the programmed cell death protein-1 (PD-1) receptor and blocks its ligands. RUBY (NCT03981796) is a two-part multicentre study in patients with recurrent or primary advanced endometrial cancer. The overall aims were to characterise the population pharmacokinetics (PopPK) from Part 1 of this study, identify relevant covariates of interest, and assess exposure-efficacy/safety (ER) relationships.

methodsA PopPK model developed using GARNET (NCT02715284) study data for dostarlimab monotherapy was externally validated with RUBY Part 1 study data. Subsequently, the model was updated with data across the two studies. Exposure-safety analyses for adverse events related to dostarlimab alone or in combination with standard of care (SOC) were modelled using logistic regression. Exposure-efficacy analysis included Cox proportional hazards analysis of the primary efficacy endpoint of progression-free survival (PFS).

resultsFor the model update, 7957 pharmacokinetics observations from 868 patients pooled from both RUBY and GARNET studies were available. The model was consistent with the previous model. Dostarlimab clearance was estimated to be 7.79% lower when dostarlimab was given as SOC combination therapy. However, no significant covariates were clinically relevant. Hepatic or renal impairment did not affect pharmacokinetics. Among the safety endpoints, only rash showed a small yet statistically significant effect (P < .05) in all subjects; however, this was not not deemed clinically relevant. There were no other clinically significant exposure-safety or exposure-PFS relationships.

conclusionsThe addition of chemotherapy to dostarlimab had limited effect on dostarlimab PopPK, with no clinically significant covariates or clinically relevant exposure-safety or exposure-PFS relationships.

Indexed as

Antibodies, Monoclonal, HumanizedEndometrial NeoplasmsModels, BiologicalNeoplasm Recurrence, LocalAdultAgedDose-Response Relationship, DrugFemaleHumansMiddle AgedProgression-Free SurvivalAntibodies, Monoclonal, Humanizeddostarlimabclinical pharmacologyoncologypharmacokineticstherapeutics

Identifiers

PMID39520048
PMCPMC11862793

What OpenQuestion holds

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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.