Anlotinib plus TQB2450 in patients with advanced refractory biliary tract cancer (BTC): An open-label, dose-escalating, and dose-expansion cohort of phase Ib trial.
Notice bibliographique
Résumé
292 Background: Anti-angiogenic agents have been clinically investigated in combination with anti-PD-1/L1 mAbs due to their immuno-modulatory effects. Anlotinib (A), a potent oral multi-target tyrosine kinase inhibitor, has anti-angiogenic properties and anti-tumor efficacy with a favorable toxicity profile. The combination of A and TQB2450 (T), an anti-PD-L1 mAb, exhibited superior tumor growth suppression compared to either monotherapy in murine models. This ongoing phase 1b study cohort is aimed to assess the safety and efficacy of A+T in pts with advanced BTC. Methods: In this study cohort, patients (pts) with previously treated, advanced BTC were enrolled. A 3+3 dose escalation was used to determine the maximum tolerated dose (MTD) and a recommended phase 2 dose (RP2D) in a dose-escalating stage. Additional pts were enrolled in a dose-expansion stage to further establish the safety and determine the preliminary efficacy. Oral A of 10 and 12 mg was administered once daily for 14 days on / 7 days off with intravenous T of 1200 mg every 3 weeks. The primary endpoint was dose-limiting toxicity (DLT) during first cycle (first 3 weeks) to estimate the MTD, RP2D and overall response rate (ORR). Tumor response was assessed according to RECIST version 1.1 and iRECIST. The Secondary endpoints were progression-free survival (PFS), disease control rate (DCR) and safety. Results:25 pts were enrolled (8 with intrahepatic cholangiocarcinoma [IHCC]; 8 with extrahepatic cholangiocarcinoma [EHCC]; 9 with gall bladder cancer [GBC]) until August 2020. Median number of prior lines of therapy was 1 (range 1-5). During dose-escalation, no DLT was observed and 12 mg anlotinib was determined as RP2D for expansion. Among 24 evaluable pts (with at least once tumor assessment), 3 had achieved complete response (CR) and 7 had partial response (PR), which were all treated by 12 mg anlotinib plus TQB2450, 8 had stable disease (SD) and 6 had progression disease (PD). ORR was 41.67% and DCR was 75%. 10 pts were still on treatment. The median PFS was 240 days (95% CI, 83~NR).Treatment-related adverse events (TRAEs) occurred in 83.3% of pts (G3/4 in 16.7% [4/24], and leading to treatment discontinuation in 4.2% [1/24]). The most common TRAEs were hypertension (33.3%), decreased white blood cell counts (25.0%), increased TBIL (20.8%), decreased neutrophil counts (20.8%), increased DBIL (12.5%), and increased IBIL (12.5%). Conclusions: A+T had a manageable safety profile and encouraging antitumor efficacy in pts with previously treated, advanced BTC. No unexpected AEs were identified beyond the established safety profile for each agent. Clinical trial information: NCT03996408.
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 | 0,001 |
| Bibliométrie | 0,000 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,001 |
| 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) | 0,004 | 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 ».