538 Updated survival of patients with previously treated metastatic uveal melanoma who received tebentafusp
Notice bibliographique
Résumé
<h3>Background</h3> Tebentafusp, a bispecific fusion protein consisting of an affinity-enhanced T cell receptor fused to an anti-CD3 effector that can redirect T cells to target gp100+ cells, has shown an overall survival benefit for patients with untreated metastatic uveal melanoma (mUM) in a Ph3 trial (NCT03070392). Metastatic uveal melanoma (mUM) is a historically treatment-refractory tumor with 1-year (yr), 2-yr and 3-yr OS rates of 37%, 15% and 9%, respectively, and median OS of 7.8 months in 2L+ patients.<sup>1</sup> In the primary analysis of the phase 2 IMCgp100–102 study (NCT02570308) enrolling patients with previously treated mUM, the 1-year overall survival (OS) rate was 62% with median OS of 16.8 months.<sup>2</sup> We present updated OS and safety after 2-year follow-up. <h3>Methods</h3> 127 HLA-A*02:01+ 2L+ mUM patients were dosed weekly with tebentafusp following intra-patient dose escalation: 20mcg dose 1, 30mcg dose 2 and 68mcg dose 3+. Primary objective was ORR and secondary objectives included safety, OS and PFS. Here we present the updated OS and safety (data cut-off 31 Mar 2021). <h3>Results</h3> Median follow-up was 29.9 mos (range 1.8 – 59.9 mos). With extended follow-up, the 1-yr, 2-yr and 3-yr OS rates were 61%, 37% and 24%, respectively (figure 1). Median OS remained unchanged at 16.8 mos (95% CI, 12.8 – 22.5 mos).Mean and median duration of treatment were 9.5 mos and 5.6 mos (0 – 47.4 mos), respectively. As previously reported, most treatment-related AEs (TRAEs) occurred early on treatment. Beyond 6 months, no TRAE led to treatment discontinuation. No new safety signals, changes in the type or treatment-related deaths were reported. Beyond 12 months, there were a total of 7 Grade (G) 3 or 4 events in 3 (7%) patients, all were temporally related to tumor progression and majority included lab abnormalities. Episodes of rash, a common tebentafusp-related AE early on-treatment, were infrequent after 6 months, with no Grade 3 or 4 events. <h3>Conclusions</h3> This study provides the longest follow-up of OS and safety of a soluble TCR therapeutic to date. Tebentafusp continued to show promising survival for 2L+ mUM patients with estimated 2-yr OS rate of 37%. Tebentafusp’s safety profile was as expected and consistent with primary analysis showing that most adverse events occur early on treatment with incidence and severity decreasing with prolonged exposure. <h3>Trial Registration</h3> NCT02570308 <h3>References</h3> Rantala ES, Hernberg M, Kivela TT. Overall survival after treatment for metastatic uveal melanoma: a systematic review and meta-analysis. <i>Melanoma Res</i> 2019;<b>29</b>:561–568. Sacco JJ, Carvajal R, Butler MO, et al. A phase (ph) II, multi-center study of the safety and efficacy of tebentafusp (tebe) (IMCgp100) in patients (pts) with metastatic uveal melanoma (mUM). <i>Ann Oncol</i> 2020;<b>31</b>: S1442–S1143. <h3>Ethics Approval</h3> The institutional review board or independent ethics committee at each center approved the trial. The trial was conducted in accordance with the Declaration of Helsinki and the International Conference on Harmonization Good Clinical Practice guidelines.
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 distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
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 tête enseignante, 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 ».