Characterization of liver function tests (LFTs) following tebentafusp (tebe) in previously treated (2L+) metastatic uveal melanoma (mUM) patients (pts).
Notice bibliographique
Résumé
e21513 Background: Tebe is a bispecific gp100-targeted T cell receptor fusion protein that can redirect polyclonal T cells to target gp100+ cells leading to T cell activation and release of inflammatory mediators. Hepatocytes do not express gp100 and tebe did not redirect T cells against normal hepatocytes in preclinical in vitro studies. However, since most mUM pts have liver metastases, tebe may result in secondary effects from localized tumor-related inflammation. Here we describe LFT kinetics and outcomes for pts in the IMCgp100-102 study (NCT02570308). Methods: 127 HLA-A*02:01+ pts with 2L+ mUM received tebe, administered weekly at the RP2D following intra-patient dose escalation (C1D1: 20μg; C1D8: 30μg; C1D15+: 68μg). Pts were eligible if ALT/AST ≤ 3 x ULN and bilirubin ≤ 1.5 x ULN. LFTs were measured at baseline (BL) and weekly prior to each dose using local laboratories. AE grading was based on CTCAE v4.03. This analysis was conducted on the primary analysis snapshot dated 04Jun20. Results: At BL,125/127 (98%) pts had ALT/AST ≤ grade(G)1 and 122/127 (96%) had liver metastasis. 68/127 (54%) had an increase in post-BL grade for ALT, AST or both. Of these 48/68 (71%) increased to G1, 9/68 (13%) to G2, 7/68 (10%) to G3, and 4/68 (6%) to G4. 67 of these 68 pts (99%) had liver metastasis and most had largest liver metastasis > 3cm (38 pts > 3 cm, 29 pts < 3cm and 1 pt without). ALT/AST increases occurred early in treatment in 36/68 (53%) including at Dose 1 (12/68; 18%), Dose 2 (10/68; 15%), or Dose 3 (14/68; 21%). In the other 32/68 pts (47%), ALT/AST increases occurred at or after Dose 4 (4-65), and most of these events (21/32; 66%) were associated temporally with increase in size of liver metastases. Among the 11 pts with G3/4 ALT/AST increases post-BL, most pts experienced these events early (Doses 1-3) (8/11; 73%) and in the context of either increase in size of liver metastases / disease progression or biliary obstruction (9/11; 82%). Most pts, 60/68 (88%), continued treatment despite an increase in ALT/AST grade. Among 8 pts who discontinued treatment, 3 were due to disease progression and 3 were due to adverse events. Median time for ALT/AST to return to BL was 9 days and there were no temporal increases in albumin or INR. Conclusions: Approximately 1/2 of tebe treated pts experienced an increase in post-BL CTCAE grade for ALT/AST. Among these pts, most ALT/AST increases were mild. Most of the pts with G3/4 ALT/AST increase (9/11) were explained by increase in size of liver metastases or biliary obstruction. Increase in LFT are not unusual at time of disease progression in mUM given high frequency of liver metastases. In summary, ALT/AST increases occurred early in about half of the pts, were generally self-limiting, permitted treatment to continue, and did not appear to impact liver synthetic function (INR/Albumin). Clinical trial information: NCT02570308.
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 | 0,000 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 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) | 0,001 | 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 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 ».