DREAMM-8: A Phase III Study of the Efficacy and Safety of Belantamab Mafodotin with Pomalidomide and Dexamethasone (B-Pd) Vs Pomalidomide Plus Bortezomib and Dexamethasone (PVd) in Patients with Relapsed/Refractory Multiple Myeloma (RRMM)
Notice bibliographique
Résumé
Introduction: Belantamab mafodotin (belamaf; GSK2857916) is a B-cell maturation antigen (BCMA)-targeting antibody-drug conjugate. In the pivotal Phase II DREAMM-2 study, single-agent belamaf demonstrated deep and durable responses with a manageable safety profile in heavily pretreated patients with RRMM (Lonial et al. Lancet Oncol 2020). Responses were sustained at 13 months of follow-up; with belamaf (2.5 mg/kg administered intravenously [IV] every 3 weeks [Q3W]), overall response rate (ORR) was 32% and median duration of response (DoR) was 11.0 months (Lonial et al. ASCO 2020 Poster 436). Preclinical data suggest synergistic antimyeloma activity of belamaf in combination with pomalidomide/dexamethasone (Pd). Preliminary data from an ongoing Phase I/II study (NCT03715478) evaluating belamaf in combination with Pd (B-Pd) suggest an acceptable safety profile and early signs of clinical activity in patients with RRMM. The DREAMM-8 study (NCT04484623) will evaluate the efficacy and safety of B-Pd compared with pomalidomide, bortezomib, and dexamethasone (PVd). Methods: This Phase III, two-arm, randomized, open-label, multicenter study will include patients with measurable RRMM who have received ≥1 prior line of therapy (including lenalidomide), with documented disease progression during or after their most recent line of treatment. Patients aged ≥18 years with Eastern Cooperative Oncology Group Performance Status 0-2, adequate organ system function, and who provide informed consent will be eligible. Patients with prior exposure to BCMA-targeted therapies or pomalidomide and those intolerant/refractory to bortezomib will be excluded. Approximately 450 patients will be randomized (1:1) to Arm A (B-Pd) or Arm B (PVd), stratified by number of prior lines of treatment, prior exposure to bortezomib, and International Staging System status. No more than 50% of participants with two or more prior lines of treatment will be enrolled. In Arm A, patients will receive belamaf 2.5 mg/kg (IV) Q4W on Day 1 in Cycle 1 (28-day cycle) followed by belamaf 1.9 mg/kg (IV) Q4W on Day 1 in Cycle 2 onwards (28-day cycles); pomalidomide 4 mg (orally [PO]) will be administered on Days 1-21 and dexamethasone 40 mg (PO) on Days 1, 8, 15, and 22 in all cycles (28-day cycles). In Arm B, pomalidomide 4 mg (PO) will be administered Q3W on Days 1-14 in all cycles (21-day cycles); bortezomib 1.3 mg/m2 will be administered subcutaneously on Days 1, 4, 8, and 11 in Cycles 1-8, and Days 1 and 8 in Cycle 9+ (21-day cycles). Dexamethasone 20 mg (PO) will be administered on the day of and the day after bortezomib. The dose level of dexamethasone in each arm will be reduced by half in patients >75 years of age. Treatment in both arms will continue until progressive disease, unacceptable toxicity, withdrawal of consent, initiation of another anticancer therapy, or end of study or death. The primary endpoint is progression-free survival (PFS; time from randomization to the earliest date of documented disease progression or death [any cause]). Minimal residual disease negativity rate is a key secondary endpoint. Additional secondary endpoints include ORR, time to response, DoR, time to progression, overall survival, PFS2 (PFS after initiation of new anticancer therapy), safety, health-related quality of life, and pharmacokinetic and pharmacodynamic parameters. The study is planned to start in August 2020. Funding: GSK (Study 207499); drug linker technology licensed from Seattle Genetics; mAb produced using POTELLIGENT Technology licensed from BioWa. Disclosures Trudel: GSK, Celgene, Janssen, Amgen, Genentech: Research Funding; Celgene, Janssen, Takeda, Sanofi, Karyopharm, Amgen Canada: Honoraria; Celgene, Amgen, GSK: Consultancy, Research Funding. Davis:GSK: Current Employment, Current equity holder in publicly-traded company. Lewis:GSK: Current Employment, Current equity holder in publicly-traded company. Bakshi:GSK: Current Employment, Current equity holder in publicly-traded company. Chopra:GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Montes de Oca:GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Ferron-Brady:GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Eliason:GSK: Current Employment, Current equity holder in publicly-traded company. Kremer:GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Gupta:GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company; Novartis: Current equity holder in publicly-traded company. Wu:GSK: Current Employment, Current equity holder in publicly-traded company.
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 | 0,003 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,002 | 0,001 |
| Méta-épidémiologie (sens large) | 0,002 | 0,002 |
| Bibliométrie | 0,001 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,001 |
| Communication savante | 0,001 | 0,001 |
| Science ouverte | 0,002 | 0,001 |
| Intégrité de la recherche | 0,002 | 0,005 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,004 | 0,002 |
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 ».