Evidence map›Paper›PMID 35064011›Full record

ArticleJournal for immunotherapy of cancer2022

Safety and antitumor activity of dostarlimab in patients with advanced or recurrent DNA mismatch repair deficient/microsatellite instability-high (dMMR/MSI-H) or proficient/stable (MMRp/MSS) endometrial cancer: interim results from GARNET-a phase I, single-arm study.

Ana Oaknin, Lucy Gilbert, Anna V Tinker, Jubilee Brown, Cara Mathews, Joshua Press, Renaud Sabatier, David M O'Malley, Vanessa Samouelian, Valentina Boni and 12 more

Registry-linked trialOpen access · goldAbstract readClinical Trial, Phase I
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal for immunotherapy of cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02715284 (A Phase 1 Dose Escalation and Cohort Expansion Study of TSR-042, an Anti-PD-1 Monoclonal Antibody, in Patients With Advanced Solid Tumors), which is not on this map. Cited by 173 papers, 10 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
173citing papers in PubMed, 10 pooled it
42.7field-weighted citation impact, top 1% 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.

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
3 · Its place in the literature

Who cites it

173 citing papers in PubMed, 10 syntheses or guidelines pooled it, 305 citations in OpenAlex.

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  16. Pembrolizumab plus Chemotherapy in Advanced Endometrial Cancer.The New England journal of medicine · 2023
    Trial
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113 more citing papers are in PubMed but not listed here.

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

22 authors at 17 institutions in 5 countries.

Ana OakninGynaecologic Cancer Programme, Vall d'Hebron Institute of Oncology (VHIO), Hospital Universitari Vall d'Hebron, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain aoaknin@vhio.net.ORCID 0000-0002-3592-7194
Lucy GilbertDepartment of Gynecologic Oncology, McGill University Health Centre Research Institute, Montreal, Quebec, Canada.
Anna V TinkerDepartment of Medicine, BC Cancer, Vancouver, British Columbia, Canada.
Jubilee BrownDivision of Gynecologic Oncology, Levine Cancer Institute, Atrium Health, Charlotte, North Carolina, USA.
Cara MathewsDepartment of Gynecological Oncology, Women and Infants Hospital of Rhode Island, Providence, Rhode Island, USA.
Joshua PressGynecologic Oncology and Pelvic Surgery, Swedish Cancer Institute, Seattle, Washington State, USA.
Renaud SabatierDepartment of Medical Oncology, Institut Paoli Calmettes, Aix-Marseille University, Marseille, France.
David M O'MalleyDepartment of Obstetrics and Gynecology, The Ohio State University James Comprehensive Cancer Center, Columbus, Ohio, USA.
Vanessa SamouelianGynecologic Oncology Service, Department of Obstetrics and Gynecology, Université de Montréal, Montreal, Québec, Canada.
Valentina BoniSTART Madrid-CIOCC, Centro Integral Oncológico Clara Campal, Hospital Universitario HM Sanchinarro, Madrid, Spain.
Linda DuskaDepartment of Gynecological Oncology, Emily Couric Clinical Cancer Center, University of Virginia, Charlottesville, Virginia, USA.
Sharad GhamandeGeorgia Cancer Center, Augusta University, Augusta, Georgia, USA.
Prafull GhatageDepartment of Gynecological Oncology, University of Calgary, Calgary, Alberta, Canada.
Rebecca KristeleitDepartment of Oncology, Guy's and St Thomas' Hospital NHS Foundation Trust, London, UK.
Charles III LeathO'Neal Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Wei GuoGlaxoSmithKline, Waltham, Massachusetts, USA.
Ellie ImGlaxoSmithKline, Waltham, Massachusetts, USA.
Sybil ZildjianGlaxoSmithKline, Waltham, Massachusetts, USA.
Xinwei HanGlaxoSmithKline, Waltham, Massachusetts, USA.
Tao DuanGlaxoSmithKline, Waltham, Massachusetts, USA.
Jennifer VenerisGlaxoSmithKline, Waltham, Massachusetts, USA.
Bhavana PothuriDepartment of Obstetrics and Gynecology, NYU Langone Health, Perlmutter Cancer Center, New York University, New York, New York, USA.
GlaxoSmithKline (United States) · USAix-Marseille Université · FRAugusta University Health · USHospital Universitario HM Sanchinarro · ESLevine Cancer Institute · USMcGill University Health Centre · CANYU Langone Health · USSpinal Cord Injury BC · CASt Thomas' Hospital · GBSwedish Medical Center · USThe Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute · USUniversité de Montréal · CAUniversity of Alabama at Birmingham · USUniversity of Calgary · CAUniversity of Virginia · USVall d'Hebron Hospital Universitari · ESWomen & Infants Hospital of Rhode Island · US

Funding

XRAY CRYSTALLOGRAPHYP30CA013148 · NCI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI Robert S Welner · 1985 to 2026
$165.9M
NCI NIH HHS P30 CA013148
6 · The paper itself

Abstract

backgroundDostarlimab is a humanized monoclonal antibody that binds with high affinity to PD-1, resulting in inhibition of binding to PD-L1 and PD-L2. We report interim data from patients with endometrial cancer (EC) participating in a phase I trial of single-agent dostarlimab.

methodsGARNET, an ongoing, single-arm, open-label, phase I trial of intravenous dostarlimab in advanced solid tumors, is being undertaken at 123 sites. Two cohorts of patients with EC were recruited: those with dMMR/MSI-H disease (cohort A1) and those with proficient/stable (MMRp/MSS) disease (cohort A2). Patients received dostarlimab 500 mg every 3 weeks for 4 cycles, then dostarlimab 1000 mg every 6 weeks until disease progression. The primary endpoints were objective response rate (ORR) and duration of response (DOR) per RECIST V.1.1, as assessed by blinded independent central review.

resultsScreening began on April 10, 2017, and 129 and 161 patients with advanced EC were enrolled in cohorts A1 and A2, respectively. The median follow-up duration was 16.3 months (IQR 9.5-22.1) for cohort A1 and 11.5 months (IQR 11.0-25.1) for cohort A2. In cohort A1, ORR was 43.5% (95% CI 34.0% to 53.4%) with 11 complete responses and 36 partial responses. In cohort A2, ORR was 14.1% (95% CI 9.1% to 20.6%) with three complete responses and 19 partial responses. Median DOR was not reached in either cohort. In the combined cohorts, the majority of treatment-related adverse events (TRAEs) were grade 1-2 (75.5%), most commonly fatigue (17.6%), diarrhea (13.8%), and nausea (13.8%). Grade≥3 TRAEs occurred in 16.6% of patients, and 5.5% discontinued dostarlimab because of TRAEs. No deaths were attributable to dostarlimab.

conclusionDostarlimab demonstrated durable antitumor activity in both dMMR/MSI-H (ORR 43.5%) and MMRp/MSS EC (ORR 14.1%) with a manageable safety profile. TRIAL REGISTRATION NUMBER: NCT02715284.

Indexed as

Antibodies, Monoclonal, HumanizedBiomarkers, TumorDNA Mismatch RepairEndometrial NeoplasmsFemaleHumansMicrosatellite InstabilityMiddle AgedAntibodies, Monoclonal, HumanizedBiomarkers, Tumordostarlimabclinical trials as topicimmunotherapyprogrammed cell death 1 receptor

Identifiers

PMID35064011
PMCPMC8785197
OpenAlexW4206897023

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

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.