Abstract CT035: Addition of Salmonella-IL2 to FOLFIRINOX for metastatic stage 4 pancreatic cancer nearly doubles median survival
Notice bibliographique
Résumé
Abstract Introduction and Background: Salmonella-IL2 (Saltikva) is an attenuated strain of orally administered Salmonella that carries the human gene for IL-2 that colonizes the tumor microenvironment and locally releases IL-2 without any untoward effects. Following significant anti-tumor responses during preclinical study in multiple tumor models; a Phase I trial in humans found a single dose to be not toxic and elevated the Natural Killer T cell populations in patients with advanced gastrointestinal (GI) cancers. Additionally, a Phase I multiple dose trial in companion dogs with metastatic osteosarcoma demonstrated a 22% complete response rate. A Phase II trial was performed studying the addition of Salmonella-IL2 to standard of care chemotherapy for stage 4 metastatic pancreatic cancer. Patients and Methods: A Health Canada and local IRB approved, non-randomized, two-arm study in patients with Stage 4 metastatic adenocarcinoma of the pancreas is currently underway. The goal is to recruit 30 patients per arm; Arm 1: Salmonella-IL2 with FOLFIRINOX and Arm 2: Salmonella-IL2 with Gemcitabine/Abraxane. The primary outcome is overall survival with secondary outcomes of response determined by CT imaging using RECIST 1.1 criteria and biomarker data. Outcomes were compared to patients with stage 4 metastatic pancreatic cancer administered FOLFIRINOX (n=37) or Gemcitabine/Abraxane (n=24) from 4 years prior to starting this trial (2016-2020) at the study site and to historical controls from the published literature. Salmonella-IL2 is orally administered concomitantly with the administration of the prescribed chemotherapy according to arm of enrollment. 109 cfu of attenuated Salmonella-IL2 was administered orally after ingestion of a gastric acid neutralizing agent and followed with 200ml of an isotonic crystalloid fluid. Results: A total of 28 patients have been enrolled into this clinical trial. 20 patients were administered Salmonella-IL2 orally every 2 weeks with FOLFIRINOX; mean age 59.4 (32-73) years; 12(60%) women, and 8 (40%) men. 8 patients were administered Salmonella-IL2 with Gemcitabine/Abraxane every 2/3 weeks; mean age is 68.8 (56-82); 6 (66.7%) women and 3 (33.3%) men. Median survival in the FOLFIRINOX arm was 24 months compared to 11.1 months in published historical controls and 13.1 months site specific controls (n=37) (P<0.05; Log Rank Test). In addition, CT imaging using RECIST 1.1 criteria demonstrated a 73% partial response rate compared to 31% in historical controls. There have been 24 serious adverse events; none of which have been attributed to the study drug. No survival advantage was observed in the Salmonella-IL2 with Gemcitabine/Abraxane arm. Conclusion: Addition of Salmonella-IL2 to FOLFIRINOX for stage 4 metastatic pancreatic cancer results in the near doubling of median survival when compared to historical and site-specific controls receiving FOLFIRNOX only. These findings strongly indicate that a larger pivotal phase 3 multicenter trial is warranted. Citation Format: Petr Kavan, Daniel A. Saltzman, Jule Muegge, Jordan Moradian, Gerald Batist. Addition of Salmonella-IL2 to FOLFIRINOX for metastatic stage 4 pancreatic cancer nearly doubles median survival [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT035.
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 | 0,000 | 0,000 |
| 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 | 0,000 |
| 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) | 0,006 | 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 ».