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Record W4382138807 · doi:10.1158/1078-0432.ccr-22-3915

Safety, Efficacy, and Biomarker Analyses of Dostarlimab in Patients with Endometrial Cancer: Interim Results of the Phase I GARNET Study

2023· article· en· W4382138807 on OpenAlexaff
Ana Oaknin, Bhavana Pothuri, Lucy Gilbert, Renaud Sabatier, Jubilee Brown, Sharad Ghamande, Cara Mathews, David M. O’Malley, Rebecca Kristeleit, Valentina Boni, Adriano Gravina, Susana Banerjee, Rowan Miller, Joanna Pikiel, Mansoor Raza Mirza, Ninad Dewal, Grace Antony, Yuping Dong, Eleftherios Zografos, Jennifer Veneris, Anna V. Tinker

Bibliographic record

VenueClinical Cancer Research · 2023
Typearticle
Languageen
FieldMedicine
TopicEndometrial and Cervical Cancer Treatments
Canadian institutionsSpinal Cord Injury BCUniversity of British ColumbiaBC Cancer AgencyUniversity of British Columbia HospitalMcGill University Health Centre
FundersEisaiAstraZeneca
KeywordsEndometrial cancerMicrosatellite instabilityMedicineInternal medicineInterim analysisBiomarkerCancerInterimOncologyClinical trialMicrosatelliteBiologyGene

Abstract

fetched live from OpenAlex

PURPOSE: This interim report of the GARNET phase I trial presents efficacy and safety of dostarlimab in patients with advanced or recurrent endometrial cancer (EC), with an analysis of tumor biomarkers as prognostic indicators. PATIENTS AND METHODS: A total of 153 patients with mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) and 161 patients with mismatch repair proficient (MMRp)/microsatellite stable (MSS) EC were enrolled and dosed. Patients received 500 mg dostarlimab every 3 weeks for four cycles, then 1,000 mg every 6 weeks until progression. Primary endpoints were objective response rate (ORR) and duration of response (DOR). RESULTS: A total of 143 patients with dMMR/MSI-H EC and 156 patients with MMRp/MSS EC were evaluated for efficacy. ORR was 45.5% (n = 65) and 15.4% (n = 24) for dMMR/MSI-H EC and MMRp/MSS EC, respectively. Median DOR for dMMR/MSI-H EC was not met (median follow-up, 27.6 months); median DOR for MMRp/MSS EC was 19.4 months. The ORRs by combined positive score (CPS) ≥1 status were 54.9% and 21.7% for dMMR/MSI-H EC and MMRp/MSS EC, respectively. ORRs by high tumor mutational burden (≥10 mutations/Mb) were 47.8% (43/90) and 45.5% (5/11) for dMMR/MSI-H EC and MMRp/MSS EC, respectively. ORR in TP53mut or POLεmut molecular subgroups was 18.1% (17/94) and 40.0% (2/5), respectively. The safety profile of dostarlimab was consistent with previous reports. CONCLUSIONS: Dostarlimab demonstrated durable antitumor activity and safety in patients with dMMR/MSI-H EC. Biomarkers associated with EC may identify patients likely to respond to dostarlimab. See related commentary by Jangra and Dhani, p. 4521.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.003
metaresearch head score (Gemma)0.004
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.097
Threshold uncertainty score0.999

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0030.004
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0010.005
Science and technology studies0.0000.001
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.394
GPT teacher head0.590
Teacher spread0.197 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations81
Published2023
Admission routes1
Has abstractyes

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