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Record W2998325113 · doi:10.1093/neuonc/noz175.032

ATIM-33. INTERIM RESULTS OF A PHASE II MULTI-CENTER STUDY OF ONCOLYTIC ADENOVIRUS DNX-2401 WITH PEMBROLIZUMAB FOR RECURRENT GLIOBLASTOMA; CAPTIVE STUDY (KEYNOTE-192)

2019· article· en· W2998325113 on OpenAlexaff
Robert Aiken, Clark Chen, Timothy F. Cloughesy, Howard Colman, Mariza Daras, Morris D. Groves, Simon Khagi, Priya Kumthekar, Frederick F. Lang, Farshad Nassiri, Shirley Ong, Rohan Ramakrishna, Adam M. Sonabend, Michael A. Vogelbaum, Gelareh Zadeh, Laura Agensky, Carin Bidwell, B. P. Watkins, Frank Tufaro, Joanna Peterkin

Bibliographic record

VenueNeuro-Oncology · 2019
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicVirus-based gene therapy research
Canadian institutionsPrincess Margaret Cancer CentreUniversity Health Network
Fundersnot available
KeywordsPembrolizumabMedicineAdverse effectOncologyInternal medicineOncolytic adenovirusOncolytic virusPhases of clinical researchCohortToxicitySurgeryImmunotherapyCancer

Abstract

fetched live from OpenAlex

Abstract BACKGROUND DNX-2401 (tasadenoturev) is a replication-competent, tumor-selective, oncolytic adenovirus. Phase I studies in adults with recurrent glioblastoma (rGBM) have demonstrated safety and encouraging clinical activity. A Phase II open-label, dose-escalating multi-center study in rGBM was initiated to evaluate DNX-2401 with pembrolizumab. Planned enrollment of 48 subjects is complete. METHODS Subjects ≥ 18 years, with a single tumor, KPS ≥ 70% and adequate organ function were enrolled sequentially into 3 cohorts of DNX-2401 (5e8vp, 5e9vp, 5e10vp). A single intratumoral injection of DNX-2401 was administered followed 7 days later by pembrolizumab (200 mg IV). Thereafter, pembrolizumab was infused Q3wks up to 24 months until progression or toxicity. 5e10vp was determined as the optimal dose and this cohort was expanded. Safety monitoring, assessments of response and survival follow-up are ongoing. RESULTS Nine subjects were treated in the escalation phase; 42 subjects received 5e10vp. No dose-limiting toxicity or unexpected safety issues were identified by an independent review committee, and there were no treatment-related deaths. Adverse events were primarily consistent with underlying disease, effects of the neuro-procedure, expected effects of pembrolizumab, and concomitant use of steroids/anticonvulsants per the standard of care. The majority of events were mild to moderate, and unrelated to DNX-2401. Headache and manageable vasogenic edema were the most common events related to DNX-2401 with pembrolizumab. For the 48 subjects who received pembrolizumab (median 6 cycles), median OS from DNX-2401 administration was 12 months (95% CI, 10.6–14.7), OS6 was 91%, and 47% experienced clinical benefit (stable disease or better). Four subjects (5e10) had a partial response (two with > 94% regression of tumor), and three (5e8; 5e10[2]) are alive > 20 months. Updated safety and efficacy results will be presented. CONCLUSIONS The data continue to demonstrate that DNX-2401 administered with pembrolizumab has an acceptable safety profile. Long-term survival and clinical benefit remain compelling.

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)0.001
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.602
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0010.000
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 head0.040
GPT teacher head0.376
Teacher spread0.336 · 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.

Study designBench or experimental
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

Citations14
Published2019
Admission routes1
Has abstractyes

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