1475 Combination of LND101, a healthy donor microbiome transplantation product, to doublet immunotherapy or immunotherapy combined with targeted therapy in metastatic renal cell carcinoma patients
Notice bibliographique
Résumé
Background Metastatic renal cell carcinoma (mRCC) is treated with dual immune checkpoint inhibitors (ICI) or ICI with a VEGF-TKI. Despite improved outcomes, some patients do not benefit from the treatment due to disease resistance or serious adverse events. We hypothesized that re-establishing a healthy microbiome in mRCC patients before and during treatment with ICI based combination therapy via healthy microbiome transplantation does not increase toxicity and improves clinical response. The PERFORM trial (NCT04163289) is a single-arm phase I study evaluating the safety of multiple microbiome transplantation procedures before and during ICI based therapy in the first-line setting (1L) for patients with mRCC. Methods In this single-centre study, 20 patients with untreated mRCC received one full dose of LND101(a full consortia healthy donor microbiome product) followed by two-half doses of LND101 before the first 3 cycles of doublet ICI or ICI combined with VEGF-TKI. The primary endpoint is the feasibility and safety of combining LND101 with standard of care. Secondary endpoints include the incidence of irAEs , objective response rate (ORR) , and finally changes in patient‘s microbiome, immune profile, and metabolome. We include a preliminary analysis of all 20 patients for the clinical outcomes. Results 16 patients received LND101 plus ipilimumab/nivolumab, 3 patients received LND101 plus pembrolizumab/axitinib, and one patient received pembrolizumab/lenvatinib. The median age was 60 years old, and 90% were male. All patients had intermediate or poor-risk disease. No dose-limiting toxicities due to LND101 were observed. Median follow-up was 22.87 months. Nine patients (45%) discontinued treatment due to irAEs to include colitis (n=3), arthritis (n=1), nephritis (n=1), diarrhea (n=1), pneumonitis (n=1), and bullous pemphigoid (n=1). Grade 3 AEs were experienced by 11 patients (55%). 18 patients had measurable disease according to RECIST 1.1 criteria and a response was confirmed in 8/18 patients (ORR 44%), including one complete response. Clinical benefit was confirmed in 13/18 patients (72%). Targeted plasma metabolomics revealed 67 metabolites elevated in patients with Grade 3 toxicity at an FDR of <0.05 relative to patients with no toxicity. Conclusions Our results suggest that microbiome modification with LND101 added to ICI-based combination therapy as 1L in patients with mRCC was safe. Furthermore, the addition of LND101 may prevent or reduce the occurrence of irAEs. For those who developed grade 3 irAEs, we observed important alterations in the gut microbiota. Finally, our results suggest that LND101 added to ICI-based combination therapy as 1L in mRCC may improve clinical outcomes. Acknowledgements Funding: Medical Oncology Research Funding, Academic Medical Organization of Southwestern Ontario Opportunities Grant, London Regional Cancer Centre Catalyst Keith Samitt Translational Cancer Research Grant and London Health Sciences Foundation. Trial Registration NCT04163289. Ethics Approval Ethics number: 114962.
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 | 0,001 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,001 |
| 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 | 0,001 | 0,001 |
| 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 ».