ILLUMINATE 301: A randomized phase III comparison of IMO-2125 with ipilimumab (ipi) versus ipi alone in subjects with anti PD 1 refractory melanoma
Bibliographic record
Abstract
Background: IMO-2125 (tilsotolimod) is a TLR9 agonist with potent immunostimulating activity. An ongoing Phase 1/2 clinical study of intratumoral tilsotolimod + ipi (NCT02644967) shows the combination to be well-tolerated over the range of tilsotolimod doses tested, with evidence of dendritic cell activation and infiltration of tumorspecific immune cells in subject samples. Clinical responses (including durable CR > 21 months) have been seen in anti-PD-1-refractory subjects. Because no therapy has been shown to prolong survival after failure of first-line anti-PD-1 immunotherapy, this study is designed to show superiority of tilsotolimod + ipi over ipi alone. Trial design: This is a randomized phase 3 global, multi-center, open-label comparison of ipi (3 mg/kg) +/- intratumoral tilsotolimod (8mg) in subjects with advanced cutaneous or mucosal melanoma with disease progression while on anti-PD-1 therapy. Eligible subjects are age ≥18 years with histologically confirmed Stage III or IV melanoma, ≥1 measurable lesion accessible for injection, ECOG ≤1, adequate organ function, and excluding those with previous TLR agonist treatment, prior ipi (except adjuvant), or CNS disease other than stable (≥4 wks) brain mets. Subjects will be randomized 1:1 to either ipi alone (Arm A) or tilsotolimod + ipi (Arm B) and stratified on the duration of prior antiPD-1 therapy (≥12 weeks/<12 weeks), stage (M1c/other), BRAF status and prior targeted therapy (TT) (BRAF wt/BRAF mut+ with TT/BRAF mut+ no TT). Primary endpoints comprise RECIST v1.1 ORR by independent central review and OS. Secondary endpoints include DRR, TTR, PFS, PRO, and safety. Treatment duration is 10 weeks (4 ipi doses) for subjects in Arm A and 24 weeks (9 tilsotolimod + 4 ipi doses) in Arm B. Final analysis (ORR and OS) will occur when 219 death events have occurred, estimated at 36 months after the first randomization. After 110 deaths, an interim analysis will be done for OS. Enrollment is planned as 308 subjects at around 80 centers in 10 countries. It is currently recruiting in the US and Australia with study initiation ongoing in EU and Canada. Clinical trial identification: NCT03445533. Legal entity responsible for the study: Idera Pharmaceuticals, Inc. Funding: Idera Pharmaceuticals, Inc. Disclosure: J. Geib, S. Rahimian, S. Swann: Employee: Idera Pharmaceuticals. A. Diab: Advisory board: Idera Pharmaceuticals. All other authors have declared no conflicts of interest.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot 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.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.003 | 0.002 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.002 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.004 |
| Insufficient payload (model declined to judge) | 0.009 | 0.002 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
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".