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ILLUMINATE 301: A randomized phase 3 study of tilsotolimod in combination with ipilimumab compared with ipilimumab alone in patients with advanced melanoma following progression on or after anti-PD-1 therapy.

2019· article· en· W2947599368 on OpenAlexaffabout
Marcus O. Butler, Caroline Robert, Sylvie Négrier, Gino K. In, John Walker, Ivana Krajsová, Victoria Atkinson, Johan Hansson, Ellen Kapiteijn, Carmen Loquai, Heather M. Shaw, Tina Cheng, Sandrine Mansard, Jean‐Jacques Grob, Massimo Guidoboni, Minal Mehta, Paolo A. Ascierto, Adi Diab

Bibliographic record

VenueJournal of Clinical Oncology · 2019
Typearticle
Languageen
FieldImmunology and Microbiology
TopicImmunotherapy and Immune Responses
Canadian institutionsPrincess Margaret Cancer CentreUniversity of TorontoBaker Hughes (Canada)University Health Network
Fundersnot available
KeywordsIpilimumabMedicineMelanomaInternal medicineOncologyClinical endpointResponse Evaluation Criteria in Solid TumorsProgressive diseaseCombination therapyPhases of clinical researchAdjuvant therapyRandomized controlled trialGastroenterologyImmunotherapyClinical trialChemotherapyCancerCancer research

Abstract

fetched live from OpenAlex

TPS9599 Background: Tilsotolimod (IMO-2125) is a Toll-like receptor (TLR) 9 agonist with potent immunostimulating activity. In an ongoing Phase 1/2 clinical study in patients with advanced melanoma who progressed on or after anti-PD-1 therapy (NCT02644967), intratumoral (IT) tilsotolimod with ipilimumab was well-tolerated, demonstrating durable responses (including complete response > 21 months), dendritic cell activation, type I interferon response, CD8+ T-cell proliferation in responders, and an abscopal effect. Methods: ILLUMINATE 301 (NCT03445533) is a randomized phase 3 global, multi-center, open-label study of IT tilsotolimod (8 mg) in combination with ipilimumab (3 mg/kg) versus ipilimumab monotherapy in patients with advanced melanoma and progression on or after anti-PD-1 therapy. Eligible patients are ≥18 years with histologically confirmed unresectable Stage III or Stage IV melanoma, ≥1 measurable lesion accessible for injection (superficial or visceral, the latter with image guidance), ECOG PS ≤1, and adequate organ function. Exclusion criteria include prior TLR agonists, prior ipilimumab (except adjuvant ≥12 weeks before progression), and CNS disease other than stable brain metastases. Patients are randomized 1:1 and stratified by duration of prior anti-PD-1 (≥12 weeks vs <12 weeks), stage (M1c vs other), and BRAF status/prior targeted therapy (TT) (BRAF wildtype vs BRAF mutation+ with TT vs BRAF mutation+ without TT). Primary endpoints are overall response rate (RECIST v1.1) by independent central review and overall survival. Secondary endpoints include durable response rate, time to response, progression-free survival, patient-reported outcomes, and safety. Patients are enrolling at sites in the United States, European Union, Australia, and Canada. References: (1) Haymaker C. Society for Immunotherapy of Cancer Annual Meeting, November 2017, National Harbor, MD; (2) Diab A, et al. European Society of Molecular Oncology Annual Meeting, October 2018, Munich, Germany. Clinical trial information: NCT03445533.

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 machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.002
metaresearch head score (Gemma)0.001
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Randomized trial · Consensus signal: Randomized trial
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.009
Threshold uncertainty score0.031

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0020.001
Meta-epidemiology (narrow)0.0020.001
Meta-epidemiology (broad)0.0030.002
Bibliometrics0.0010.001
Science and technology studies0.0010.001
Scholarly communication0.0010.001
Open science0.0010.001
Research integrity0.0020.004
Insufficient payload (model declined to judge)0.0090.002

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 head0.025
GPT teacher head0.373
Teacher spread0.348 · 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 source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designRandomized 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

Citations13
Published2019
Admission routes2
Has abstractyes

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