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Record W2900303949 · doi:10.1093/neuonc/noy148.019

ATIM-24. INTERIM RESULTS OF A PHASE II MULTICENTER STUDY OF THE CONDITIONALLY REPLICATIVE ONCOLYTIC ADENOVIRUS DNX-2401 WITH PEMBROLIZUMAB (KEYTRUDA) FOR RECURRENT GLIOBLASTOMA; CAPTIVE STUDY (KEYNOTE-192)

2018· article· en· W2900303949 on OpenAlexaff
Gelareh Zadeh, Frederick F. Lang, Mariza Daras, Timothy F. Cloughesy, Howard Colman, Shirley Ong, Rohan Ramakrishna, Michael A. Vogelbaum, Morris D. Groves, Farshad Nassiri, Livia Frederick, Karen Gammon, Sheila Fulling, Kari Anne Rowland, Erin Mitchell, Brett Ewald, Frank Tufaro, Joanna Peterkin

Bibliographic record

VenueNeuro-Oncology · 2018
Typearticle
Languageen
FieldMedicine
TopicGlioma Diagnosis and Treatment
Canadian institutionsToronto Western HospitalUniversity of TorontoUniversity Health Network
Fundersnot available
KeywordsOncolytic virusPembrolizumabInterimMedicineOncolytic adenovirusGlioblastomaOncologyInternal medicinePhases of clinical researchVirologyCancer researchClinical trialCancerImmunotherapyGeography

Abstract

fetched live from OpenAlex

DNX-2401 (tasadenoturev) is a replication-competent, tumor-selective, oncolytic adenovirus. A dose-escalating, Phase II study of a single intratumoral injection of DNX-2401 with pembrolizumab to determine optimal dose, safety and efficacy is ongoing and enrolling up to 48 patients with recurrent glioblastoma. Key inclusion criteria include patients with a single lesion at first or second recurrence for which resection is not possible or planned. In a dose-escalation design, a single intratumoral dose of DNX-2401 (5e8vp, 5e9vp, 5e10vp) is administered via cannula, followed 7 days later by 200 mg pembrolizumab Q3wk for up to 24 months or until confirmed progression, intolerable toxicity, or study withdrawal. Tumor response is assessed every 4 weeks for 6 months and every 8 weeks thereafter. As of 01May2018, 23 patients have been treated, with 17 at the optimal dose of 5e10vp DNX-2401. The median age and KPS at entry was 52 years (26–65) and 90 (80–100), respectively. The most frequent related grade 3–4 AEs across cohorts are headache (30%), fatigue (9%), and increased GGT (9%) consistent with disease or immune activation. Transient grade 1–3 lymphopenia has also been observed. Several cases of vasogenic edema have been managed with steroid tapers or low-dose bevacizumab. No patient has died or discontinued due to study treatment. The median treatment duration is 5.1 months for evaluable patients treated with DNX-2401 and pembrolizumab (N=15). Preliminary efficacy includes two partial responses and 100% 9-month survival for the first 7 patients treated. DNX-2401 followed by pembrolizumab is well tolerated, and data emerging for disease control and survival are encouraging. Updated results will be presented.

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)0.000
metaresearch head score (Gemma)0.001
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Non-randomized trial · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.371
Threshold uncertainty score0.901

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.000
Science and technology studies0.0000.001
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
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 head0.042
GPT teacher head0.368
Teacher spread0.326 · 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 designNon-randomized trial
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

Citations33
Published2018
Admission routes1
Has abstractyes

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