Livmoniplimab with or without budigalimab in patients with advanced solid tumors: Results from the combination therapy in the urothelial carcinoma dose expansion cohort.
Notice bibliographique
Résumé
617 Background: Checkpoint inhibitors (CPIs) are approved for treating advanced urothelial carcinoma (UC). However, many patients (pts) present with/develop resistance and new therapies are urgently needed. The release of active transforming growth factor beta-1 (TGF-β1) from the glycoprotein-A repetitions predominant (GARP):TGF-β1 complex on regulatory CD4+ T cells suppresses antitumor response. Inhibiting active TGF-β1 release from the GARP:TGF-β1 complex could address CPI resistance in UC. Livmoniplimab (livmo), an antibody targeting the GARP:TGF-β1 complex, is being investigated as monotherapy and in combination with budigalimab (budi), an anti–PD-1 antibody, in a phase 1 study (NCT03821935). We present expanded results from the livmo + budi dose expansion (EXP) in pts with UC. Methods: This is a global, dose escalation (ESC) and EXP study in pts (≥18 yr) with advanced solid tumors; the UC EXP cohort enrolled pts with UC of the bladder and urinary tract that progressed on platinum-based therapy and a CPI in the metastatic setting. The maximum tolerated dose was not reached in the ESC part, and pts in EXP cohorts received the maximum administered dose of 1500 mg livmo (IV, Q2W) and 500 mg budi (IV, Q4W) until disease progression/intolerable toxicity. The primary efficacy endpoint was ORR per RECIST v1.1. Additional efficacy outcomes included DOR and PFS. Safety and PK were also assessed. Results: As of 30 Mar 2023, 200 pts were enrolled, 57 in ESC and 143 in livmo + budi EXP, including 48 pts in the UC EXP cohort. For the UC cohort, median age was 66 yr (49–85), 77% of pts were male, 40%/60% had ECOG PS 0/1, and median prior lines of therapy was 3 (1–9). Livmo PK was not impacted by budi coadministration and no on-treatment anti-drug -antibodies were detected. TEAEs were observed in 100% of pts; most common were pruritus (44%) and decreased appetite (21%). Grade 3/4 TEAEs occurred in 23 pts (48%), with anemia and malignant neoplasm progression (10% each) being the most common; 11 pts (23%) died but no death was related to livmo or budi. TRAEs were observed in 29 pts (60%)/26 pts (54%) for livmo/budi; pruritus (livmo: 33%; budi: 31%) and rash (17% for both) were most common. Among the 45 response evaluable pts, best response rate was 24% (n=11; 95% CI: 12.9, 39.5); confirmed ORR was 18%. Median restricted mean DOR was 7.9 mo (95% CI: 6.0, not reached); median/75th percentile PFS were 1.8 mo (95% CI: 1.6, 4.2)/8.0 mo (95% CI: 2.7, 14.9). Conclusions: Livmo + budi had manageable safety and promising efficacy in pts with advanced UC that progressed on platinum-based therapy and a CPI. ORR in the UC cohort (pts postprogression with platinum + CPI therapy) are comparable with ORR in CPI-naive pts with pembrolizumab (KEYNOTE-045) and nivolumab (CheckMate 275) monotherapy. A subpopulation of pts in the UC cohort had a durable response to livmo + budi. Clinical trial information: NCT03821935 .
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 | 0,002 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,002 | 0,002 |
| Bibliométrie | 0,000 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,001 | 0,001 |
| Science ouverte | 0,001 | 0,000 |
| Intégrité de la recherche | 0,001 | 0,002 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 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 ».