LEGEND: A phase 1/2 study of detalimogene voraplasmid (EG-70), an intravesical monotherapy for patients with high-risk non–muscle-invasive bladder cancer (NMIBC).
Bibliographic record
Abstract
TPS4631 Background: High-risk NMIBC is generally treated with adjuvant intravesical Bacille Calmette-Guérin (BCG). However, ~50% of patients experience recurrence and/or progression afterwards and are considered unresponsive. Detalimogene voraplasmid (EG-70) is an investigational, non-viral, non-integrating, intravesically administered gene therapy designed to elicit local stimulation of anti-tumor immune responses in the bladder and drive durable efficacy in NMIBC, while mitigating the risk of systemic toxicities from immune stimulation. The Phase 1 (dose-escalation) portion of the first-in-human Phase 1/2, open-label, multicenter study (LEGEND; NCT04752722) of detalimogene voraplasmid is complete. The Phase 2 dose was identified, treatment was generally well tolerated, with an overall complete response (CR) rate of 73% [Kalota S, et al. AUA 2024]. Herein, we describe the ongoing Phase 2 portion of the study, which opened to enrollment in May 2023, which recently added a new cohort of BCG-unresponsive HG Ta/T1 papillary only (no carcinoma in situ [CIS]) disease. Methods: Eligibility criteria: age ≥18 years; ECOG PS 0−2; NMIBC, with/without resected coexisting papillary tumors, ineligible for, or elected not to undergo, cystectomy; satisfactory bladder function. Patients receive detalimogene voraplasmid 0.8 mg/mL in 50 mL (intravesical administration, Weeks 1, 2, 5 & 6, 12-week cycle) for 4 cycles, and patients with CR at the end of the 4 th cycle will enter maintenance treatment to receive 2 instillations per cycle (at Weeks 1 and 2) for up to another 8 cycles: BCG-unresponsive with CIS (Cohort 1); BCG-naïve with CIS (Cohort 2A) or BCG-exposed with CIS (Cohort 2B); BCG-unresponsive NMIBC with high-grade papillary disease without CIS (Cohort 3). Phase 2 primary endpoints: efficacy (CR rate at Week 48); safety. Secondary endpoints: progression-free survival; CR rate at Weeks 12, 24, 36, and 48; duration of response. The study is being conducted in accordance with the ethical principles of the Declaration of Helsinki and is consistent with ICH/GCP. All patients provide written informed consent. The Phase 2 portion of the study is enrolling and will recruit approximately 300 patients across all cohorts, from sites in the USA, Canada, Europe, and the Asia-Pacific region. Clinical trial information: NCT04752722 .
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.002 | 0.003 |
| Insufficient payload (model declined to judge) | 0.044 | 0.007 |
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".