Initial results of phase I study of DCC-2618, a broad-spectrum KIT and PDGFRa inhibitor, in patients (pts) with gastrointestinal stromal tumor (GIST) by number of prior regimens
Notice bibliographique
Résumé
Background: DCC-2618, a kinase switch control inhibitor, broadly inhibits mutations in KIT exons 9, 11, 13, 14, 17 and 18. Based on clinical activity observed in heavily pretreated GIST pts in a Phase 1 study, DCC-2618 is being evaluated in a Phase 3 study, INVICTUS (NCT03353753), in ≥ 4th line pts. Given the breadth of inhibition of KIT mutations and favorable tolerability profile, the Phase 1 study included expansion cohorts to assess clinical benefit in 2nd and 3rd line GIST pts in advance of the expected initiation of a second Phase 3 study in 2nd line GIST pts by the end of 2018. Methods: The Phase 1 study includes a dose-escalation component testing oral DCC-2618 dosed QD or BID in 28 day cycles and an expansion phase using the RP2D of 150 mg QDin 6 cohorts, including cohorts for GIST pts based on prior regimens (2nd/3rd, 4th/>4th). RECIST response assements based on local assessment of CT scans were performed every 2 cycles. Results: At the cut off of April 18, 150 GIST pts were enrolled at dose levels of ≥ 100 mg/d with KIT (141 pts) or PDGFRa- (8 pts) -driven GIST. One pt had SDH-deficient GIST. 114 GIST pts were treated at the 150 mg QD dose, including 19, 27, and 68 pts who previously received 1, 2 or ≥ 3 prior lines of therapy, respectively. For the 114 GIST pts, ORR was 14%, 3-month DCR was 70%, mPFS was 24 weeks with 56% of the pts censored. For the 46 evaluable pts in 2nd/3rd line, ORR was 22%, 3-month DCR was 81% and mPFS was 36 weeks with 61% of the pts censored. Updated ORR, DCR and mPFS will be presented. Grade 3/4 adverse effects (regardless of attribution, in > 1 pt) for all 114 pts treated at 150 mg QD included asymptomatic lipase increase 11, anemia 4, hypertension 3, blood bilirubin increased 3, diarrhea 2, abdominal pain 2, back pain 2, hypophosphatemia 2, hyponatremia 2, hyperkalemia 2. Conclusions: DCC-2618 demonstrated encouraging clinical benefit and a favorable tolerability profile in GIST pts treated in the 2nd line or later. Clinical benefit as measured by ORR, DCR and mPFS was greater in 2nd/3rd line pts compared to more heavily pretreated pts. Preliminary data from the Phase 1 expansion supports further testing in the planned Phase 3 study in 2nd line GIST. Clinical trial identification: NCT02571036. Legal entity responsible for the study: Deciphera Pharmaceuticals, Inc. Funding: Deciphera Pharmaceuticals, Inc. Disclosure: S. George, M. Heinrich, P. Chi, M. von Mehren, M. Gordon, N. Somaiah, F. Janku: Research sponsored: Deciphera Pharmaceuticals, Inc.; Scientific advisory board: Deciphera Pharmaceuticals, Inc. A. Razak, K.N. Ganjoo, J. Wolf, J. Rodon Ahnert: Research sponsored: Deciphera Pharmaceuticals, Inc. J.C. Trent: Scientific advisory board: Deciphera Pharmaceuticals, Inc. R. Ruiz-Soto, O. Rosen: Employee: Deciphera Pharmaceuticals, Inc.
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 | 0,001 |
| 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 | 0,001 |
| 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 ».