Pimicotinib in tenosynovial giant cell tumor (TGCT): Efficacy, safety and patient-reported outcomes of phase 3 MANEUVER study.
Notice bibliographique
Résumé
11500 Background: TGCT is a rare, locally aggressive mesenchymal neoplasm, driven by the overproduction of colony-stimulating factor 1 (CSF-1), and is often associated with joint pain, swelling, stiffness and functional impairment. The high rate of recurrence and the significant tumor burden, particularly in the diffuse variant, highlight the necessity for an effective systemic treatment. Pimicotinib (pimi) is an oral, highly selective and potent small-molecule inhibitor of CSF-1 receptor (CSF-1R). We report the results from the double-blind Part 1 of MANEUVER, the first global Phase 3 trial to recruit TGCT patients (pts) from Asia, EU and North America (NA) who were candidates for systemic therapy. Methods: MANEUVER (NCT05804045) is a Phase 3, randomized, double-blind, placebo (pbo)-controlled trial evaluating efficacy and safety of pimi in pts with TGCT. In Part 1, pts received pimi 50 mg QD or pbo (2:1) for 24 weeks. Primary endpoint was objective response rate (ORR) by blinded independent review committee (BIRC) per RECIST v1.1 at Week 25. Key secondary endpoints included ORR by tumor volume score (TVS) and clinical outcome assessments (COAs) at Week 25: mean change from baseline in range of motion (ROM), worst stiffness, Brief Pain Inventory (BPI) worst pain and PROMIS physical function. Safety was also evaluated. Results: At the data cutoff of Sep 23, 2024, all of the planned 94 pts were enrolled (China = 45; EU = 28; NA = 21), with 63 randomized to pimi and 31 to pbo.Median age was 40.0 years (range: 18-69); 68.1% were female; disease location mainly in knee (50.0%), ankle (14.9%) or hip (13.8%). ORR by BIRC per RECIST v1.1 and TVS at Week 25 was significantly higher for pimi vs pbo (54% vs 3.2% and 61.9% vs 3.2%, respectively; both p < 0.0001). Statistically significant and clinically meaningful improvements were observed with pimi vs pbo for all COAs: active ROM (15.64 vs -0.07; p = 0.0003), worst stiffness (-3.00 vs –0.57; p < 0.0001), BPI worst pain (-2.32 vs –0.23; p < 0.0001) and PROMIS physical function (5.63 vs 2.23; p = 0.0074). Significantly more pain responders (BPI-30) were observed with pimi vs pbo (63.5% vs 16.1%; p < 0.0001). Treatment efficacy was consistent across pts from different regions and ethnicities. Most TEAEs were low grade, consistent with the known mechanism of action of CSF-1R inhibitors and led to a low rate of dose reduction (7.9%, 5/63 pts) and treatment discontinuation (1.6%, 1/63 pt). There was no evidence of cholestatic hepatotoxicity or drug-induced liver injury. Conclusions: MANEUVER is the first randomized pivotal study in TGCT to demonstrate > 50% ORR by RECIST v1.1 at Week 25 in a diverse, global patient population. Pimi produced statistically significant and clinically meaningful improvements in physical function and symptoms, representing an effective, well-tolerated and convenient daily treatment for patients with TGCT and addressing a critical unmet need. Clinical trial information: NCT05804045 .
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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 | 0,002 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,002 | 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 | 0,001 |
| 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 ».