DREAMM-4: evaluating safety and clinical activity of belantamab mafodotin (belamaf) in combination with pembrolizumab in patients with relapsed/refractory multiple myeloma: Session: Multiple Myeloma
Notice bibliographique
Résumé
Introduction: Single-agent belamaf (GSK2857916; BLENREP) has shown deep and durable responses and a manageable safety profile in patients with heavily pretreated RRMM (DREAMM-2, NCT03525678, Lancet Oncol 2020). Immune surveillance in patients with RRMM is often blunted through the PD-1/PDL-1 axis; PDL-1 being highly expressed on MM cells. PD-1 inhibitor pembrolizumab, may augment immune responses to belamaf-induced immunogenic cell death. DREAMM-4 (NCT03848845) is an ongoing Phase I/II, two-part study assessing safety and efficacy of belamaf plus pembrolizumab in patients with RRMM. Methods: Patients had ≥3 prior lines of therapy, including anti-CD38 treatment. Planned enrollment for both parts is up to 40 patients. Part 1 (dose escalation) evaluates 2.5 or 3.4 mg/kg belamaf plus 200 mg pembrolizumab in up to 12 patients to establish the recommended Phase II dose (RP2D) of this combination. Both drugs are given IV Q3W for up to 35 cycles. Part 1 interim analyses (IA) are presented. Part 2 (dose expansion) will confirm safety and assess clinical activity at the RP2D; overall response rate (ORR; ≥partial response) is the primary endpoint. Results: As of 4 Feb 2020, 6 and 7 patients were enrolled at the 2.5 and 3.4 mg/kg doses, respectively (1 patient replaced as per protocol). In the 2.5 and 3.4 mg/kg groups, median (range) prior lines of therapy were 7.5 (3–13) and 5.0 (3–8), and 3/6 (50%) and 1/7 (14%) patients had high-risk cytogenetics. No dose-limiting toxicities were reported in either group. All patients in both groups experienced adverse events (AEs) and treatment-related AEs. The most frequent AEs of any grade and Grade 3/4 are reported in the Table. Serious AEs (SAEs) were reported in 50% (3/6) of patients in the 2.5 mg/kg group (n=1 had a treatment-related SAE) and 43% (3/7) of patients in the 3.4 mg/kg group (n=3 had a treatment-related SAE). No Grade 5 AEs occurred. Keratopathy (microcyst-like epithelial changes [MECs], with/without symptoms) was the primary reason for dose delays (2.5 mg/kg group: 67%; 3.4 mg/kg group: 14%) and dose reductions (2.5 mg/kg group: 17%; 3.4 mg/kg group: 0%). The ORR was 67% and 14% in the 2.5 and 3.4 mg/kg groups, respectively (Table). PK data and free soluble BCMA levels were consistent with previous studies. Conclusion: Belamaf plus pembrolizumab demonstrated a manageable safety profile and clinical activity in patients with RRMM. Keratopathy (MECs) was the most frequent AE, consistent with belamaf studies, and managed with dose modifications. Part 1 IA supports continuation with Part 2 of this study. Funding: GSK (205207) in collaboration with Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. Drug linker technology licensed from Seattle Genetics; monoclonal antibody produced using POTELLIGENT technology licensed from BioWa. Encore Statement: This abstract was accepted and previously presented at EHA 2020 (Nooka et al EP955). Resubmitted with permission.
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 | 0,001 | 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 | 0,000 |
| Communication savante | 0,000 | 0,001 |
| 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 ».