A Phase 1b Study to Assess the Combination of Selinexor and Daratumumab in Patients with Relapsed / Refractory Multiple Myeloma Previously Exposed to Proteasome Inhibitors (PI) and Immunomodulatory Drugs (IMiDs)
Notice bibliographique
Résumé
Abstract Introduction - Selinexor is a first-in-class Selective Inhibitor of Nuclear Export (SINE) compound that binds and inactivates Exportin 1 (XPO1). Selinexor, as a single agent, or in combination with PIs or IMiDs, has shown anti-MM activity in patients (pts) with relapsed or refractory multiple myeloma (RRMM). Daratumumab, an anti-CD38 monoclonal antibody, is approved for the treatment of In this study, we aim to explore the safety and efficacy of selinexor in combination with daratumumab and low dose dexamethasone (SDd) in pts with RRMM. Methods - This is a phase 1b/2 dose escalation study using a standard 3+3 design. The primary endpoint is to determine the maximum tolerated dose and recommended phase 2 dose (RP2D) for SDd. Pts were eligible if they had RRMM and had received ≥ 3 prior therapies, including a PI and IMiD. Selinexor was independently dosed escalated in 2 concurrent cohorts: once-weekly (QW, at 100 mg) or twice-weekly (BIW, at 60 mg) regimens. Daratumumab (16 mg/kg IV) was administered QW and dexamethasone (dex) was given orally 40 mg QW or 20 mg BIW. Results - As of 15-Jul-2017, 6 pts (4 males / 2 females) have been enrolled. Three pts each have been enrolled into the 100 mg QW and 60 mg BIW cohorts. Pts have a median age of 66 years and a median of 3 (range, 3 - 7) prior treatment regimens. Adverse events include: nausea, thrombocytopenia, and anemia. Three pts in the 100 mg QW cohort tolerated the regimen well with no DLT. The 3 pts in the 60 mg BIW cohort have not yet completed DLT evaluation. Based on preliminary tolerability and efficacy, an additional 3 pts will be enrolled in the 100 mg QW cohort to establish the RP2D dose. All 3 pts from the 100 mg QW cohort had a partial response (2 unconfirmed) after C1 and remain on study. Conclusions - Selinexor 100 mg QW, can be combined safely with daratumumab and dex. The activity observed in the first 3 pts is promising with all 3 pts responding to therapy. Enrollment is ongoing and updated data from 100 mg QW cohort, 100 mg QW expansion, and full phase 1 will be updated and presented. Disclosures Gasparetto: Celgene: Research Funding; Janssen, BMS, Celgene: Other: Travel, accommodations, or other expenses paid or reimbursed; Janssen, BMS, Celgene, Takeda: Honoraria; Janssen, BMS, Celgene: Consultancy. Lentzsch: Amgen: Consultancy; BMS: Consultancy; Caelum Biosciences: Other: leadership position and stock. Bensinger: Bayer: Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Sanofi: Consultancy, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Acetylon: Research Funding; BMS: Consultancy, Research Funding. Bahlis: Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Sebag: Celgene, Janssen: Consultancy. Chen: Celgene: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Amgen: Honoraria; Abbvie: Honoraria. Kauffman: Karyopharm Therapeutics Inc: Employment, Equity Ownership, Membership on an entity's Board of Directors or advisory committees. Shacham: Karyopharm Therapeutics Inc: Employment, Equity Ownership, Membership on an entity's Board of Directors or advisory committees. Jeha: Karyopharm Therapeutics: Employment. Saint-Martin: Karyopharm Therapeutics: Employment. Shah: Karyopharm Therapeutics: Employment.
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 | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,001 | 0,001 |
| Communication savante | 0,001 | 0,001 |
| Science ouverte | 0,001 | 0,000 |
| Intégrité de la recherche | 0,001 | 0,004 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,005 | 0,001 |
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 ».