Nemtabrutinib, a Noncovalent Reversible BTK Inhibitor in Relapsed or Refractory Follicular Lymphoma: Results from the Phase 2 Bellwave-003 Study
Notice bibliographique
Résumé
Introduction: Covalent Bruton tyrosine kinase inhibitors (BTKi) have demonstrated monotherapy activity in relapsed/refractory follicular lymphoma (FL), although response rates and progression free survival (PFS) have been limited. Nemtabrutinib is a once daily, potent, noncovalent, reversible BTKi with a distinct kinase profile, inhibiting BTK and other B-cell receptor relevant kinases. Here, we present the safety and efficacy results from the phase 2 BELLWAVE-003 study (NCT04728893) of nemtabrutinib at the recommended phase 2 dose (RP2D) in participants (pts) with relapsed/refractory (R/R) FL. Methods: The multicenter, open-label, single-arm phase 2 BELLWAVE-003 study enrolled pts with R/R CLL/SLL, Richter transformation, mantle cell lymphoma, marginal zone lymphoma, FL, and Waldenstrom's macroglobulinemia. Pts with R/R FL received nemtabrutinib at RP2D of 65 mg once daily until unacceptable toxicity, disease progression, or withdrawal. The primary endpoint was objective response rate by investigator assessment according to Lugano 2014 criteria. Additional endpoints included duration of response, progression-free survival (PFS), overall survival (OS), and safety and tolerability. The data cut-off date was April 19, 2024. Results: At data cut-off, 36 pts with R/R FL treated at RP2D were enrolled. The median (range) follow-up was 6.1 mo (0.2-13.9). These pts had a median age of 58 years (range 33-78), 18 (50%) were female. At enrollment, 2 (6%) pts had Follicular Lymphoma International Prognostic Index (FLIPI) score of 0-1 (low), 12 (33%) had FLIPI score 2 (intermediate), and 22 (61%) had FLIPI score 3-5 (high); 33 (92%) pts had Lugano stage III/IV disease The median (range) number of prior lines of therapy was 4 (1-11). All pts had prior chemoimmunotherapy, 32 (89%) had prior lenalidomide, and 11 (31%) had prior PI3K inhibitor. The median (range) time on therapy was 2.8 mo (0.03-9.5), with 16 (44%) pts on therapy at data cut-off. Among 29 efficacy evaluable pts, the ORR was 41% (95% CI, 24-61), including 1 (3%) with CR and 11 (38%) with PR; 6 (21%) pts had stable disease. The median (range) DOR was 5.8 mo (1.5-not reached [NR]) with median (range) time to response of 2.8 mo (range 2.6-5.4). Median PFS in the as treated population was 5.5 mo (95% CI, 2.8-NR). Median OS was NR (95% CI, 10.4-NR), with 6-mo OS rate of 100%. Any-grade adverse events (AEs) occurred in 31 (86%) pts, most commonly neutropenia in 10 (28%) pts, decreased platelet count (8 [22%], and anemia (7 [19%]). Grade 3-4 AEs occurred in 13 (36%) pts, with grade 3-4 decreased platelet count in 3 (8%) pts, thrombocytopenia in 3 (8%) pts, neutropenia in 3 (8%) pts, and anemia in 2 (6%) pts. No atrial fibrillation or other arrhythmia was observed. Dose reductions due to an AE occurred in 1 (3%) pt (sepsis), and discontinuation due to an AE in 3 (8%) pts (thrombocytopenia, drug related toxicity, urticaria). There were no deaths due to an AE. Conclusion: Nemtabrutinib demonstrated promising antitumor activity in a heavily refractory population of pts with FL post chemoimmunotherapy and immunomodulatory therapy. Nemtabrutinib was well tolerated, and no new safety signals were identified. Enrollment and follow-up are ongoing.
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 | 0,002 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,001 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,001 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,001 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,003 | 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 ».