Results of a Phase 2 Trial Evaluating Efficacy and Safety of Entospletinib (GS-9973) in Patients with Mantle Cell Lymphoma
Notice bibliographique
Résumé
Abstract Introduction: Entospletinib (GS-9973) is an orally bioavailable, selective inhibitor of spleen tyrosine kinase (Syk). Syk is a mediator of B-cell receptor signaling in normal and transformed B-cells. Targeting the B-cell receptor (BCR)-signaling pathway has been the focus in many types of B-cell related hematological malignancies including mantle cell lymphoma (MCL). Methods: This reports the MCL cohort in a phase 2 trial that more broadly evaluated the efficacy and safety of entospletinib (800 mg BID) in patients with relapsed and refractory hematological malignancies (NCT01799889). Tumor response was assessed per Cheson 2007 criteria with imaging planned at weeks 8, 16, 24, and then every 12 weeks. The primary endpoint was PFS at week 16. All efficacy data were assessed by an Independent Review Committee. Results: A cohort of 39 patients with MCL was enrolled. The median age was 72 years (range: 49-92), 64% were male, and a median number of prior regimens were 2 (range: 1-6). Prior therapy included anti-CD20 antibodies (95%), alkylating agents (95%; bendamustine 44%), and anthracyclines (77%). Three patients (8%) have received ibrutinib either as investigational drug (n = 1) or as an approved drug (n = 2), and 1 patient (3%) received idelalisib. Median duration of treatment was 21 weeks (range: 1-87), with 1 patient continuing on treatment. Thirty-five (90%) patients were evaluable for tumor response. Four patients (10%) discontinued prior to initial tumor assessment: death (n = 1), disease progression (n = 2) and investigator's discretion (n = 1). The most common TEAEs (any grade/≥gr 3, independent of causality) and common lab abnormalities are summarized in Table 1. There were 4 TEAEs that led to study drug discontinuation (all n = 1): cardiac arrest, pruritus, pyrexia, and maculopapular rash. Six deaths were reported, none of which were related to study drug. The ORR was 15% (90% CI: 6.9%, 28.1%), with 6 (15%) patients achieving a PR and 23 (59%) patients maintaining a stable disease. The PFS rate at week 16 was 66% (95% CI: 46%, 79%). Median PFS was 5.6 months (95% CI: 3.6 months, 8.9 months). These results are based on data analysis of June 28, 2016. Conclusion: Entospletinib was well tolerated and demonstrated modest activity in patients with relapsed or refractory MCL. Further development of entospletinib in MCL will focus on the development of combination therapy. Figure 1 Waterfall Plot of Best % Change from Baseline in SPD. Figure 1. Waterfall Plot of Best % Change from Baseline in SPD. Figure 2 Kaplan-Meier Curve of Progression-Free Survival. Figure 2. Kaplan-Meier Curve of Progression-Free Survival. Disclosures Sharman: Gilead Sciences, Inc.: Honoraria, Research Funding. Kolibaba:Amgen: Research Funding; Celgene: Research Funding; Cell Therapeutics: Research Funding; Genentech: Research Funding; GSK: Research Funding; Janssen: Research Funding; Acerta: Research Funding; Gilead: Consultancy, Research Funding; Novartis: Research Funding; Pharmcyclics: Research Funding; Seattle Genetics: Research Funding; TG Therapeutics: Honoraria, Research Funding. Shustov:Seattle Genetics: Research Funding; BMS: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; SPECTRUM: Consultancy, Research Funding; Novartis: Research Funding. Nay:Gilead Sciences, Inc.: Honoraria; Janssen: Honoraria, Other: Advisory board; Celgene: Honoraria, Other: Advisory board; Amgen: Other: Advisory board; Lyndbeck: Honoraria; BMS: Honoraria. Zhang:Gilead Sciences: Employment, Equity Ownership. Shi:Gilead Sciences, Inc.: Employment, Equity Ownership. Forero:University of Alabama at Birmingham: Research Funding. Assouline:BMS: Speakers Bureau; Lundbeck: Consultancy; Janssen: Consultancy, Speakers Bureau; Pfizer: Speakers Bureau.
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 | 0,001 | 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) | 0,000 | 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 ».