Abstract 2223: Phase I clinical trial combining camu camu prebiotic enriched with castalagin modulates bile acids and metabolites in combination with cancer immunotherapy in patients with treatment-naïve lung cancer and PD-1 refractory melanoma (NCT05303493)
Notice bibliographique
Résumé
Abstract Introduction: Several strategies to improve immune checkpoint inhibitors (ICI) activity are under evaluation. Pre-clinical murine studies have shown the potential of castalagin, a prebiotic polyphenol extracted from Camu Camu (CC) berry to beneficially shift the microbiome and metabolites leading to enhanced ICI response. We tested CC, an approved natural product, in a trial combined with ICI in melanoma (MM) and non-small cell lung cancer (NSCLC). Methods: We completed a phase I trial combining 1.5g daily of CC in oral capsules, started 7 days prior ICI initiation and continued for 3 months. The study included 2 arms: (1) advanced treatment-naïve NSCLC patients (pts) with PD-L1 <50% receiving anti-PD-1 and platinum doublet chemotherapy (chemo), and (2) ICI-refractory MM pts rechallenged with ICI. The primary endpoint was safety, the secondary endpoint included disease control rate (DCR; rate of partial response (PR), complete response, and stable disease (SD)). Exploratory analyses focused on CC’s impact on the microbiome composition and HPLC analysis for metabolites with particular focus on bile acid (BA) production. In parallel, murine experiments with supplementation of castalagin were conducted and in vitro assays were performed to explore its link to the BA pathway. Results: Of the 29 pts enrolled, none experienced AE related to CC alone. Among 14 NSCLC pts receiving CC+ICI+chemo, incidence of grade 3 adverse events (AE) was 29%, the DCR reached 43% (all PR), with 0 patient experiencing primary progressive disease. In the refractory MM cohort, incidence of grade 3 AE related to CC+ICI was 16%. Among the 12 evaluable pts, the DCR was 35% with 1 achieving a PR, while 2 had durable SD over an 18-month period. We measured BA concentrations in the feces of NSCLC pts and observed a rise in both primary and conjugated BA post-CC. In addition, metabolomic analysis revealed higher phenylbutyric acid level in the plasma of NSCLC. In MM, conjugated BA were enriched in the plasma post-CC. Similarly, administration of castalagin in a murine model resulted in elevated levels of DCA and UDCA in feces and serum. In mice, the modulation of FXR (main BA receptor) inhibited castalagin antitumor activity, highlighting its reliance on BA pathway. Moreover, stimulation of liver cells with urolithins metabolites of castalagin, induced the upregulation of key BA transporters Ostα/β, Tgr5 receptor and Cyp8b1 enzyme. Conclusion: Administration of CC showed no increase in toxicities with encouraging preliminary efficacy to ICI in pts mainly in the setting of refractory MM. Ongoing analyses aim to identify how microbial signature can shift BA pool and their functional role in clinical responses. These results position castalagin as a novel experimental therapeutic target in immuno-oncology. Citation Format: Jade Maillou, Reilly Pidgeon, Diogjena Katerina Prifti, Meriem Messaoudene, Sreya Duttagupta, Myriam Benlaifaoui, Yongjia Hu, Alysé Filin, Mayra Ponce, Wiam Belkaid, Julie Malo, Guido Kroemer, Sylvère Durand, Olivier Barbier, Nathalie Daaboul, Normand Blais, Mustapha Thefe, Marie Florescu, Rahima Jamal, Wilson Miller, Antoine Desilets, Bastien Castagner, Arielle Elkrief, Bertrand Routy. Phase I clinical trial combining camu camu prebiotic enriched with castalagin modulates bile acids and metabolites in combination with cancer immunotherapy in patients with treatment-naïve lung cancer and PD-1 refractory melanoma (NCT05303493) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 2223.
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 | 0,001 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,001 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,001 |
| 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 ».