P864: A PHASE 1 STUDY OF BELANTAMAB MAFODOTIN IN COMBINATION WITH STANDARD OF CARE IN NEWLY DIAGNOSED MULTIPLE MYELOMA: AN INTERIM ANALYSIS OF DREAMM-9
Notice bibliographique
Résumé
Topic: 14. Myeloma and other monoclonal gammopathies - Clinical Background: Belantamab mafodotin (belamaf) is a B-cell maturation antigen-binding antibody-drug conjugate that eliminates myeloma cells via direct cell killing and anti-myeloma immune responses. DREAMM-9 (NCT04091126) is an ongoing Phase 1, randomized, dose and schedule evaluation study. Herein, we report updated interim-analysis data. Aims: DREAMM-9 aims to evaluate belamaf plus bortezomib, lenalidomide, and dexamethasone (VRd) in adult patients with transplant-ineligible newly diagnosed multiple myeloma and to establish the recommended dose for future development of belamaf combination therapies in the first-line setting. Methods: Belamaf dose cohorts are shown in the Table. VRd was given every 3 weeks until cycle 8, and Rd every 4 weeks thereafter (Q3/4W). Following safety data from Cohorts 2–5, Cohorts 6–7 were opened in parallel (randomized 1:1) and have shorter follow-up (Table). Safety was the primary endpoint; efficacy and tolerability were secondary endpoints. Minimal residual disease (MRD) was assessed by next-generation sequencing (10-5). Results: As of data cutoff (October 20, 2022), 93 patients were treated across Cohorts 1–7. Median age (range) was 73 (51–88) years, 55% of patients were male, and 84% were white. The most commonly reported non-ocular adverse events (AEs) across all cohorts were thrombocytopenia (46%), constipation (36%), diarrhea (34%), and peripheral sensory neuropathy (31%). Overall, belamaf-related Grade ≥3 AEs occurred in 35% of patients and led to belamaf dose reductions in 7% and dose delays in 63% of all treated patients. Grade ≥3 ocular AEs (keratopathy and visual acuity [KVA] scale) occurred in 53% of all patients and led to dose reductions in 12% and dose delays in 52% of overall patients. Fatal AEs occurred in 7 patients, all unrelated to study treatment. Efficacy results and ocular AEs are summarized in the Table: 100% of patients responded in Cohort 1 (1.9 mg/kg Q3/4W) and Cohort 3 (1.9 mg/kg Q6/8W). Median time to very good partial response or better (≥VGPR) ranged from 2.1 to 3.1 months across cohorts. Highest MRD negativity rates (≥VGPR) were seen in Cohort 1 (83%) and Cohort 3 (67%). Summary/Conclusion: This updated interim analysis demonstrates that belamaf plus VRd has no new safety signals and provides early and deep anti-myeloma responses in patients with transplant-ineligible newly diagnosed multiple myeloma, with high MRD negativity rates. Funding: GSK (Study 209664); drug linker technology licensed from Seagen Inc.; monoclonal antibody produced using POTELLIGENT Technology licensed from BioWa. This abstract was previously submitted to the American Society of Clinical Oncology (ASCO) Annual Meeting, June 2–6, 2023, and is submitted on behalf of the original authors with their permission. ©2023 American Society of Clinical Oncology, Inc. Reused with permission. All rights reserved. Table. Efficacy and Safety Summary - Cohorts 1 1.9 mg/kg Q3/4W n=12 2 1.4 mg/kg Q6/8W n=12 3 1.9 mg/kg Q6/8W n=12 4 1.0 mg/kg Q3/4W n=15* 5 1.4 mg/kg Q3/4W n=13 6 1.4 mg/kg then 1.0 mg/kg Q9/12W n=14 7 1.9 mg/kg then 1.4 mg/kg Q9/12W n=15* Grade ≥3 ocular AEs (KVA; N=91), % 83 58 92 57 85 7 0 Median follow-up, months 27.6 16.0 16.2 15.3 15.2 2.5 2.0 ORR, % ≥CR VGPR PR MR/SD 100751780 9283808 100831700 80532077 92622380 791421437 53727207 MRD[-], % ≥CR ≥VGPR 7583 3333 5867 3333 4646 714 07 *Safety population n=14. AEs, adverse events; CR, complete response; KVA, keratopathy and visual acuity scale; MR, minor response; MRD, minimal residual disease; ORR, overall response rate; OS, overall survival; PR, partial response; Q, every; SD, stable disease; VGPR, very good partial response; W, weeks. Keywords: Multiple myeloma, Phase I, Minimal residual disease (MRD), B-cell maturation antigen
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 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 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 | 0,000 |
| 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 ».