320 Integrated efficacy and safety analysis of letetresgene autoleucel, a T-cell receptor T-cell therapy, across clinical trials of patients with synovial sarcoma and myxoid/round cell liposarcoma
Notice bibliographique
Résumé
Background Letetresgene autoleucel (lete-cel) is an investigational T-cell receptor therapy targeting the NY-ESO-1 cancer/testis antigen, which is highly expressed in synovial sarcoma (SyS) and myxoid (with or without round cell) liposarcoma (MRCLS). An integrated analysis of lete-cel efficacy and safety was conducted using pooled data from three single-arm trials of patients with advanced SyS and MRCLS.Methods The integrated efficacy and safety analysis included data from two pilot trials ( NCT01343043, NCT02992743) and the pivotal IGNYTE-ESO trial (NCT03967223), plus an ongoing long-term follow-up study (NCT03391778). Eligibility: previously treated advanced (unresectable/metastatic) SyS or MRCLS, human leukocyte antigen (HLA)-A*02:01, *02:05, or *02:06-positive, NY-ESO-1 expression, baseline ECOG 0–1, and received any dose of lete-cel. Treatment-naïve patients (SyS, n=5) were excluded from the efficacy analyses. Response was assessed by independent review in all three studies. Key efficacy endpoints: overall response rate (ORR) per RECIST v1.1, best overall response, duration of response (DoR), time to response, disease control rate, progression-free survival (PFS), overall survival (OS) and persistence. Key safety endpoints: adverse events (AEs), serious AEs, AEs of special interest, deaths, laboratory assessments, and replication competent lentivirus. Data was pooled and outputs present combined data and subgroup analyses summarized by indication and overall.Results A total of 178 sarcoma patients were enrolled, of which 147 received lete-cel and were included in the pooled safety population (97 [66.0%] with SyS, 50 [34.0%] with MRCLS) and 142 were evaluable for efficacy. At baseline in the overall population, median age was 40.0 years (range, 10–73), 44.4% were female, and 92.3% were White; baseline characteristics were similar across SyS and MRCLS. Independent reviewer-assessed ORR was 43.0% (61/142) overall, 45.7% (42/92) in SyS, and 38.0% (19/50) in MRCLS ( table 1). Median DoR and PFS in overall/SyS/MRCLS was 7.16/6.74/7.16 months and 5.29/4.04/7.69 months, respectively. Median OS was 20.50 months overall. The integrated safety analysis will be presented but to date, lete-cel treatment has a manageable safety profile consistent with T-cell therapy and lymphodepletion, including transient serious cytopenias, rash, and mild/moderate cytokine release syndrome.Conclusions The integrated analyses provide a comprehensive report of the efficacy and safety profile of lete-cel in the largest population to date. Efficacy as assessed by ORR, PFS, and OS was comparable across indications, further supporting the validity of lete-cel as an effective therapy for patients with advanced SyS and MRCLS.Acknowledgements This analysis was funded by Adaptimmune. Writing and editorial support was by Chloe Koulouris, PhD, of Envision Pharma, Inc. (Horsham, UK), funded by Adaptimmune.Trial Registration Lete-cel pilot trial in SyS (CT.gov, NCT01343043) Lete-cel pilot trial in MRCLS (CT.gov, NCT02992743) Lete-cel phase 2 IGNYTE-ESO (CT.gov NCT03391778)Ethics Approval This was a secondary analysis of existing clinical trial data and did not require ethical approval. Written informed consent was obtained from participants at the time each trial was conducted.Abstract 320 Table 1Integrated efficacy analysis outcomes from previously treated patients with SyS or MRCLS who received lete-cel treatment in interventional clinical trials (independent review)
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,004 | 0,002 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,002 | 0,002 |
| Bibliométrie | 0,001 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,001 |
| Communication savante | 0,001 | 0,001 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,001 | 0,002 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 0,001 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».