Glofitamab step-up dosing (SUD): Complete response rates in updated efficacy data in heavily pretreated relapsed/refractory (R/R) non-Hodgkin lymphoma (NHL) patients (pts).
Notice bibliographique
Résumé
7519 Background: Glofitamab (RG6026), a T-cell-engaging, bispecific, full-length antibody, allows bivalent binding to CD20 (B-cells), and monovalent binding to CD3 (T-cells). In NP30179 (NCT03075696), an ongoing multicenter, Phase I dose-escalation and expansion study, 0.6–25mg glofitamab fixed-dosing with obinutuzumab pretreatment (Gpt), showed high, durable complete responses and manageable safety in heavily pretreated R/R NHL (Dickinson, et al. EHA 2020). Glofitamab SUD, in addition to Gpt, allowed dose escalation up to 30mg to maximize efficacy, while mitigating cytokine release syndrome (CRS) (Hutchings, et al. JCO 2021). We present updated efficacy data from glofitamab monotherapy SUD cohorts. Methods: Gpt (1000mg) was given to pts 7 days pre-glofitamab initial dose. Intravenous SUD of glofitamab was given on Day (D) 1 and 8 of Cycle (C) 1 and then at the target dose from C2D1 (2.5/10/16mg or 2.5/10/30mg); treatment continued for up to 12 cycles, every 21 days. Response rates were based on the Lugano criteria (Cheson, et al. JCO 2014). Results: Fifty-two pts received glofitamab SUD; 17 and 35 pts received 2.5/10/16mg and 2.5/10/30mg, respectively. Twenty-eight pts (53.8%) had aggressive NHL (aNHL) and 24 pts had indolent NHL (iNHL). Pts had a median age of 68 (44–85) years and received a median of 3 (1–12) prior lines of therapy. Forty (76.9%) and 38 (73.1%) pts were refractory to their most recent and any prior CD20 therapy, respectively. After a median follow-up of 6.3 months, an updated efficacy analysis was conducted on December 1, 2020. For pts with aNHL (N = 28), the best overall response (OR) and complete metabolic response (CMR) rates were 64.3% and 57.1%, respectively; a trend of improved response was observed with increased target dose, with a CMR rate of 71.4% at 2.5/10/30mg (N = 14). Notably, 4/5 pts (80%) with mantle cell lymphoma (2.5/10/16mg, n = 2; 2.5/10/30mg, n = 2) had CMR. For aNHL, 13/16 CMRs are ongoing, with 8 CMRs lasting > 3 months. For pts with iNHL (N = 24), OR and CMR rates were 79.2% and 70.8%, respectively; 14/17 CMRs are ongoing, with 10 CMRs lasting > 3 months. As of August 3, 2020, common adverse events (52 pts) were CRS (63.5%), neutropenia (38.5%), and pyrexia (32.7%). CRS was mostly confined to C1: 24/50 pts had CRS after 2.5mg; 20/49 pts after 10mg; 2/16 and 8/32 pts had CRS after 16 and 30mg (C2D1), respectively. Grade [Gr] 1 and 2 CRS was reported in 18 (34.6%) and 12 (23%) pts, respectively; 3 pts had Gr 3 CRS; none had Gr 4/5 events (ASTCT 2019). Updated data, including biomarker data on baseline CD20 expression and CD8 levels in the tumor, will be presented. Conclusions: Updated data for glofitamab monotherapy SUD show higher preliminary response rates than previously reported in pts with R/R NHL who have failed multiple lines of therapy. CRS was mostly manageable, of low grade, and confined to the first cycle of treatment. Clinical trial information: NCT03075696.
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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 | 0,002 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,001 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,001 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 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 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 ».