BRACELET-1 (PrE0113): Inducing an inflammatory phenotype in metastatic HR+/HER2- breast cancer with the oncolytic reovirus pelareorep in combination with paclitaxel and avelumab.
Notice bibliographique
Résumé
1012 Background: In preclinical studies, the oncolytic reovirus pelareorep promoted an inflammatory tumor microenvironment (TME) by promoting greater infiltration of tumor infiltrating lymphocytes and upregulating PD-1/PD-L1 expression, potentially increasing the efficacy of immune checkpoint blockade. The addition of pelareorep to paclitaxel (PTX) was associated with improved survival (10.4 vs. 17.4 mos., HR = 0.65, p = 0.1) in a prior trial, with the greatest benefit in patients (pts) with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) disease (N = 57; 10.8 vs. 21.0 mos., HR 0.60, p = 0.1). Methods: This is a randomized phase 2 study in pts with HR+/HER2- metastatic breast cancer. Patients must have progressed on at least one hormone therapy with a CDK4/6 inhibitor. After a safety run-in for Cohort 3, patients were randomized 1:1:1 to PTX-alone (Cohort 1), PTX + pelareorep (Cohort 2), or PTX + pelareorep + avelumab (Cohort 3). The primary endpoint was overall response rate (ORR) at week 16 according to RECIST v1.1 without formal comparison across groups. Toxicity, progression-free survival (PFS) and overall survival were secondary endpoints. Blood samples were collected at cycle 1-day 1 (C1D1), C2D1 and C4D1, and T-cell receptor sequencing was performed. Results: Forty-eight pts were enrolled between June 2020 and June 2022. Median age was 55.5 yrs, range 37-74. Forty pts (83%) had visceral disease. Six pts (12%) previously received everolimus, and 3 alpelisib. Thirteen pts (27%) received prior taxanes in the neo/adjuvant setting. Three pts who withdrew consent prior to starting therapy and 2 pts who discontinued treatment after week 1 were considered non-responders and were censored for PFS. The most common pelareorep-associated toxicities were fever, chills, and flu-like infusion reactions, which were occasionally severe enough to require hospitalization in 5 (15%) pts despite acetaminophen prophylaxis. Nine pts (33%) discontinued pelareorep and 6 (35%) discontinued avelumab due to toxicity. Pelareorep increased T-cell repertoire turnover, with identification and expansion of new and pre-existing T-cell clones by C2D1. Conclusions: The addition of pelareorep to PTX is an active regimen with a high 6-month PFS rate worthy of further study. One third of patients discontinued either pelareorep or avelumab due to toxicity, highlighting the need for attentive supportive care. Survival data is maturing. Clinical trial information: NCT04215146 . [Table: see text]
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 distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,002 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 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) | 0,000 | 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 tête enseignante, 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 ».