Updated results from the trastuzumab deruxtecan (T-DXd) 5.4 mg/kg triplet combination of DESTINY-Gastric03 (DG-03): First-line (1L) T-DXd with fluoropyrimidine (FP) and pembrolizumab in advanced/metastatic HER2-positive (HER2+) esophageal adenocarcinoma, gastric cancer (GC), or gastroesophageal junction adenocarcinoma (GEJA).
Notice bibliographique
Résumé
448 Background: T-DXd is a HER2-directed antibody-drug conjugate; T-DXd 6.4 mg/kg monotherapy is approved for patients with metastatic HER2+ GC/GEJA who have received a prior trastuzumab-based regimen. Preliminary results from DG-03 Part 2 showed feasibility and promising antitumor activity with 1L T-DXd 6.4 mg/kg (arm D) or 5.4 mg/kg (arm F) with FP and pembrolizumab in patients with esophageal adenocarcinoma/GC/GEJA. T-DXd 6.4 mg/kg and FP with pembrolizumab was associated with higher than expected toxicity; alternatively, early safety data from T-DXd 5.4 mg/kg triplet combination showed a manageable safety profile. We report updated results for arm F from DG-03 Part 2 with an approximate time-matched analysis with arm D. Methods: DG-03 (NCT04379596) is a Phase 1b/2 multicenter, open-label, dose-escalation (Part 1) and -expansion (Parts 2, 3, and 4) study. In Part 2, patients with HER2+ (immunohistochemistry [IHC] 3+ or IHC 2+/in situ hybridization–positive by local testing) esophageal adenocarcinoma/GC/GEJA, irrespective of programmed cell death ligand 1 status, and no prior treatment for metastatic disease were enrolled. In arm D, patients received T-DXd 6.4 mg/kg intravenous (IV) infusion every 3 weeks (Q3W) and FP (5-fluorouracil [5-FU] 600 mg/m 2 continuous IV or capecitabine [cape] 1000 mg/m 2 twice daily [BID]) with pembrolizumab 200 mg IV Q3W; in arm F, patients received T-DXd 5.4 mg/kg IV Q3W and FP (5-FU 600 mg/m 2 continuous IV or cape 750 mg/m 2 BID) with pembrolizumab 200 mg IV Q3W.Primary endpoint was confirmed objective response rate by investigator assessment (INV) per RECIST 1.1. Secondary endpoints included duration of response by INV and progression-free survival by INV. Safety and tolerability were also assessed. Results: A time matched analysis was performed to compare the efficacy of arm D (n=43), data cut-off (DCO) October 27, 2022, and arm F (n=32), DCO May 6, 2024, given the limited follow up of the 5.4mg/kg. The median duration of follow up for the two cohorts was 4.1 months and 4.6 months for arm D and arm F, respectively. Objective response rate for arm D was 41.9% and 59.4% for arm F. Median PFS was 6.4 months (95% CI: 5.0, NC) for arm D and 5.8 months (95% CI: 5.6, NE) for arm F. At DCO, the median overall survival in both arms was not reached. Updated time matched safety and efficacy data will be provided at the time of presentation. Conclusion: The time matched analysis shows that lowering the dose of T-DXd to 5.4 mg/kg from 6.4 mg/kg and lowering the starting dose of capecitabine, did not result in decrease in efficacy of the combination of T-DXd + FP + pembrolizumab. Funding: This study is sponsored by AstraZeneca in collaboration with Daiichi Sankyo. In March 2019, AstraZeneca entered into a global development and commercialization collaboration agreement with Daiichi Sankyo for trastuzumab deruxtecan (T-DXd; DS-8201). Editorial acknowledgment: Under guidance of the authors and in accordance with Good Publication Practice, medical writing and editorial support was provided by Carmen Grimaldos, PhD, of Helios Medical Communications, part of Helios Global Group, and was funded by AstraZeneca. Clinical trial information: NCT04379596 .
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 | 0,002 | 0,003 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,003 | 0,000 |
| Bibliométrie | 0,001 | 0,002 |
| 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 | 0,002 |
| 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 ».