Abstract C077: Updated results of phase 1 study of ripretinib (DCC-2618), a broad-spectrum KIT and PDGFRA inhibitor, in patients with gastrointestinal stromal tumor (GIST) by line of therapy (NCT02571036)
Notice bibliographique
Résumé
Abstract Objective: Ripretinib (DCC-2618) is a kinase switch control inhibitor designed to broadly inhibit KIT and PDGFRA mutations. Based on clinical activity observed in heavily pretreated patients (pts) with GIST in a Phase 1 study (NCT02571036), ripretinib is under evaluation in two Phase 3 studies: INVICTUS (NCT03353753) in ≥4th-line pts and INTRIGUE (NCT03673501) in 2nd-line pts, each at the recommended dose of 150 mg once daily (QD). This abstract reports updated results from the escalation and expansion phases of the Phase 1 study for pts treated with ≥100 mg daily dose. Methods: The Phase 1 study includes a dose-escalation phase that tested oral ripretinib QD or twice daily (BID) in 28-day cycles, followed by an expansion phase with the recommended Phase 2 dose (RP2D) of 150 mg QD in 6 cohorts, including cohorts for pts with GIST based on prior regimens (2nd/ 3rd, 4th, and >4th-line). Local Response Evaluation Criteria in Solid Tumors (RECIST) response assessments were performed every 2 cycles and pts who progressed per RECIST in the expansion cohorts were allowed to dose escalate to 150 mg BID. Results: At a cut-off date of March 01, 2019, 179 pts with GIST in the escalation and expansion phases (median follow-up of 10.4 months; range, 0.1–32.3) were enrolled at dose levels of ≥100 mg daily with KIT-driven (169 pts), PDGFRA-driven (9 pts), or wild-type-driven GIST (1 pt). Of 178 pts with GIST treated at the ≥100 mg daily dose (1 pt was not included in the intent-to-treat population as the pt only participated in the food effect portion of the study), there were 37 2nd-line pts, 31 3rd-line pts, 60 4th-line pts, and 50 >4th-line pts. The objective response rate (ORR) by best response was 30% in 2nd-line pts (n=11; includes 3 unconfirmed responses), 23% in 3rd-line pts (n=7; includes 3 unconfirmed responses), and 11% in ≥4th-line pts (n=12; includes 4 unconfirmed responses); responses ≥4th-line include 15% in 4th-line pts (n=9; includes 4 unconfirmed responses) and 6% in >4th-line pts (n=3; includes no unconfirmed responses). In 2nd-line pts, the disease control rate (DCR) was 31% (n=9) at 52 weeks. The median progression-free survival (mPFS) was 42 weeks in 2nd-line pts, 40 weeks in 3rd-line pts, and 24 weeks in ≥4th-line pts (includes 30 weeks in 4th-line pts and 16 weeks in >4th-line pts). In 2nd-line pts, the median duration of response was 80 weeks and the median duration of treatment was 44 weeks. For any line, 13% of pts (n=24) experienced treatment-emergent adverse events (TEAEs) leading to study treatment discontinuation, 17% of pts (n=31) experienced TEAEs leading to dose reduction and 49% (n=88) had TEAEs leading to study drug interruption. Grade 3 or 4 TEAEs in >5% of pts were lipase increased (18%; n=33), anemia (11%; n=20), hypertension (7%; n=13), and abdominal pain (6%; n=11). Conclusion: In this Phase 1 study, ripretinib demonstrated encouraging clinical benefit (as measured by mPFS, ORR [best response] and DCR) and was generally well-tolerated in pts with GIST treated in the 2nd-line or later. Preliminary data from this Phase 1 study further supports testing in the ongoing Phase 3 study in 2nd-line GIST. Citation Format: Ping Chi, Filip Janku, Michael Heinrich, Kristen Ganjoo, Hans Gelderblom, Michael Gordon, Robin Jones, Albiruni Razak, Jonathan Trent, Margaret von Mehren, Simin Hu, Ying Su, Rodrigo Ruiz-Soto, Suzanne George. Updated results of phase 1 study of ripretinib (DCC-2618), a broad-spectrum KIT and PDGFRA inhibitor, in patients with gastrointestinal stromal tumor (GIST) by line of therapy (NCT02571036) [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2019 Oct 26-30; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2019;18(12 Suppl):Abstract nr C077. doi:10.1158/1535-7163.TARG-19-C077
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 | 0,007 | 0,006 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,002 | 0,002 |
| Bibliométrie | 0,001 | 0,001 |
| Études des sciences et des technologies | 0,001 | 0,000 |
| Communication savante | 0,002 | 0,001 |
| Science ouverte | 0,002 | 0,001 |
| Intégrité de la recherche | 0,001 | 0,003 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,008 | 0,003 |
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 ».