Lete-cel in patients with synovial sarcoma or myxoid/round cell liposarcoma: Planned interim analysis of the pivotal IGNYTE-ESO trial.
Bibliographic record
Abstract
2500 Background: Letetresgene autoleucel (lete-cel) is an autologous engineered T cell receptor therapy targeting the NY-ESO-1 cancer testis antigen highly expressed in synovial sarcoma (SyS) and myxoid/round cell liposarcoma (MRCLS). Lete-cel pilots showed promising efficacy in patients (pts) with NY-ESO-1–expressing SyS or MRCLS. We report the planned interim analysis (IA) of IGNYTE-ESO substudy 2 (SS2). Methods: IGNYTE-ESO is an ongoing, international, open-label Phase 2 trial (NCT03967223). SS2 planned enrollment/apheresis of ~87 human leukocyte antigen (HLA)-A*02:01, *02:05, or *02:06-positive pts aged ≥10 years with NY-ESO-1–expressing (≥30% staining at 2+/3+ per IHC) metastatic or unresectable SyS or MRCLS, with a 0–1 ECOG PS. Pts must: have started/received anthracycline based chemotherapy before apheresis, have progression on their last prior line of therapy (bridging therapy excluded) and measurable disease per RECIST v1.1 before lymphodepletion (LD). LD (fludarabine 120 mg/m2, cyclophosphamide 2700–3600 mg/m2, cumulative) was dose reduced for predefined risk factors. Dose range: (1–15)×109 transduced cells. Primary endpoint: overall response rate (ORR) per RECIST v1.1 by central independent review. IA efficacy population: the 1st 45 evaluable pts who had ≥6 months follow-up. Safety population: pts who had received lete-cel at time of the IA. Pre-defined success criterion at IA: 14 responders of 45 evaluable pts with ≥6 months follow-up. Primary analysis occurs when the 60th dosed pt has 12 months follow-up. Results: As of the March 2, 2023 IA, 98 pts were apheresed, 73 pts received lete-cel (safety) and 45 pts were evaluable for efficacy. Median age was 46.0 years (range 18–68), 23 (51%) had SyS. Median transduced cell dose was 6.40×109 cells (range 2.1–11). ORR: 18 of 45 (40%, multiplicity-adjusted 99.6% CI: 20.3%, 62.3%) pts by independent review (2 CR, 16 PR); 9 of 23 (39%) for pts with SyS, 9 of 22 (41%) for pts with MRCLS. Median duration of response: 10.6 months (95% CI: 3.3, NE; data are immature with 12 of 18 pts censored). Adverse events (AEs) were consistent with those previously observed with lete-cel. Most common AEs (all grades) were cytokine release syndrome (CRS) in 65 (89%), neutropenia in 53 (73%), thrombocytopenia in 46 (63%), rash in 39 (53%), anemia in 38 (52%) and leukopenia in 36 (49%) pts. Grade ≥3 cytopenias occurred in 63 (86%) pts, including grade 5 neutropenia in 1 (1%) pt. 9 (12%) pts had grade 3 CRS and 17 (23%) pts had grade 3 rash (no grade 4 or 5 in either). Immune effector cell-associated neurotoxicity (ICANS) occurred in 3 (4%) pts; all grade 1. Conclusions: IGNYTE-ESO SS2 met the primary endpoint success criterion at this planned IA, with a 40% ORR consistent across SyS and MRCLS, and a known safety profile of hematologic toxicity and CRS. This supports the potential of lete-cel as a novel therapy for pts with advanced or metastatic SyS and MRCLS. Clinical trial information: NCT03967223 .
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How this classification was reachedexpand
Direct model labels (unvalidated)
Per-model category and study-design labels from the labeling rounds. They are machine output, unvalidated, and the disagreement between models ships as data. No study design here is MEDLINE-validated yet.
| Model arm | Categories | Study design | Confidence |
|---|---|---|---|
| gemma | no category Domain: not available · Genre: Empirical About the Canadian research system: no · About a Canadian topic: no | Non-randomized trial | low |
| gpt | no category Domain: not available · Genre: Empirical About the Canadian research system: no · About a Canadian topic: no | Non-randomized trial | medium |
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 | 0.003 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.002 |
| 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 | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.005 | 0.001 |
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, unvalidatedLabeled directly by 2 models reading the full record.
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".