BOLD-100-001 (TRIO039): A phase 1b/2a study of BOLD-100 in combination with FOLFOX chemotherapy in patients with pre-treated advanced gastric and biliary tract cancer: Efficacy and safety analysis.
Notice bibliographique
Résumé
4098 Background: BOLD-100 is a first-in-class ruthenium-based anticancer agent in Phase 1b /2a clinical development for the treatment of advanced gastrointestinal (GI) cancers in combination with FOLFOX. BOLD-100 demonstrated synergy in established preclinical models in combination with various anticancer therapies, particularly in resistant cell lines. Methods: This is a prospective, Phase 1b/2a study of BOLD-100 in combination with FOLFOX for the treatment of gastrointestinal cancers including biliary tract (BTC) and gastric (GC) cancers. Patients are administered BOLD-100+FOLFOX on day 1 of each 14-day cycle. Four cohorts are treated at the BOLD-100 RP2D of 625 mg/m2 with FOLFOX until progressive disease or unacceptable toxicity. BTC and GC pt cohort data are presented. The primary objective is to evaluate the efficacy of BOLD-100 in three clinical endpoints (PFS, OS, and ORR). Disease Control Rates (DCR) for each cohort are also determined. Bayesian modelling is used to continually reassess these endpoints, the posterior probability of superiority to an historical landmark for each endpoint. Results: As of 31Dec22, 22 pts with advanced metastatic BTC and 13 pts with advanced GC median age 61 in each cohort were treated. The BTC pts received a median of 2 prior systemic therapies while the GC patients had a median of 3. All patients presented with stage IV disease. 21/22 BTC patients received prior GEM/CIS and while on study a median of 4 cycles BOLD-100+FOLFOX [range 1-19]. Median PFS was 5.0 [3.1, 8.9] months, median OS 7.3 [4.2, 14] months, ORR 6% [1,23] and DCR 83% [62, 95] in 18 evaluable patients. Four pts remain on treatment and 3 in follow-up. 10/13 GC pts were previously treated with a platinum; currently there are 9 evaluable patients. To the data cut-off, patients received a median of 6 cycles BOLD-100+FOLFOX [1-16]. Median PFS was 5.5 [2.8, 13] months and median OS 15 [5.4, 63] months. Two pts achieved a partial response and 6 pts had stable disease for an overall DCR of 89% (8/9 [59%,99%]). Five pts remain on treatment with an additional 6 in follow-up. Study treatment was well tolerated. For the 35 treated patients, 33 reported 1 or more treatment-emergent adverse events (AEs), most commonly neutrophil count decreased (n = 15, 43%), nausea (n = 12, 34%), fatigue (n = 10, 29%), and anemia (n = 10, 29%). Most of the AEs were grade (G) 1-2. 14 patients (40%) reported G3/4 neutrophil count decreased. Conclusions: BOLD-100 plus FOLFOX is an active and well-tolerated treatment regimen in the heavily pre-treated Stage IV biliary tract and gastric cancer study populations. There were no new safety signals. The preliminary mPFS, mOS, ORR and DCR data in this interim analysis demonstrate significant improvement over the currently available therapies for these difficult to treat advanced GI cancers. Clinical trial information: NCT04421820 .
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) | 0,001 | 0,001 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,001 |
| Communication savante | 0,001 | 0,000 |
| Science ouverte | 0,001 | 0,000 |
| Intégrité de la recherche | 0,001 | 0,003 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,003 | 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 ».