Abstract CT110: Safety and anti-tumor activity of a novel Treg depleter RG6292, as a single agent and in combination with atezolizumab in patients with solid tumors
Notice bibliographique
Résumé
Abstract Background RG6292 is the first anti-human CD25 antibody developed to specifically deplete human Tregs while preserving IL-2R STAT5 signaling and Teff activity. Methods Patients with advanced/metastatic solid tumors and without standard treatment options were enrolled in dose escalation studies and received RG6292 i.v. Q3W as monotherapy (S1: NCT04158583) or in combination with atezolizumab 1200 mg Q3W (S2: NCT04642365) until disease progression or unacceptable toxicities to determine the maximum tolerated dose (MTD) and/or optimal biological dose, safety and preliminary clinical activity. DLT window was 4 weeks and dose increments were determined by a Bayesian-based continuous reassessment method (CRM) with overdose control. Adverse events (AEs) were graded by NCI CTCAE v5.0. Tumors were assessed by RECIST 1.1 every 8 weeks in the first year and then every 12 weeks. Results As of 27th May, 2022, 76 patients have been treated with RG6292 monotherapy (dose ranging from 0.3 - 165 mg). Six DLTs were reported, including rash, papular rash, rash macular-papular, AST elevation and ALT elevation. MTD is 165 mg. Seventy-five patients (99%) experienced at least one AE. The most common AEs were pruritus (32%), rash (29%) and fatigue (29%). Thirty-five patients (46%) experienced grade ≥ 3 AEs and 2 patients discontinued from study treatment due to AEs. Fourteen patients (18%) experienced grade ≥ 3 TRAEs. No AEs led to a fatal outcome. Median treatment duration was 43 days. Twenty-three patients have SD as best overall response. Forty-eight patients have been treated with RG6292 (dose ranging from 0.3 - 160 mg) in combination with atezolizumab. Two DLTs were reported, including immune system disorder and maculopapular rash. MTD has not been reached. Forty-seven patients (98%) experienced at least one AE. The most common AEs reported were pruritus (44%), rash (33%) and fatigue (33%). Twenty patients (42%) experienced grade ≥3 AEs and 2 patients discontinued from study treatment due to AEs. Five patients (10%) experienced grade ≥3 TRAEs. No AEs led to a fatal outcome. Median treatment duration was 54 days. Pruritus and rash were expected AEs and easily managed withtopical steroids or short course, low dose systemic steroids. Two patients have PR and 19 patients have SD as best overall response. Conclusion RG6292 is well tolerated and has a manageable safety profile as a single agent and in combination with atezolizumab. The preliminary safety and clinical activity from dose-escalation warrant further investigation of RG6292. Citation Format: Valentina Gambardella, Michael Ong, Maria Esperanza Rodriguez Ruiz, Jean-Pascal Machiels, Miguel Fernandez de Sanmamed, Josep Maria Tabernero, Anna Spreafico, Daniel J Renouf, Stephen J Luen, Rachel Galot, Bernard Doger de Speville Uribe, Emiliano Calvo Aller, Aung Naing, Samira Curdt, Eva Rossmann, Tamara Tanos, Kevin Smart, Maria Amann, Yuying Xie, Gabriel Schnetzler, Christophe Boetsch, Vaios Karanikas, Theresa Kolben, Linxinyu Xu, Kristoffer S Rohrberg. Safety and anti-tumor activity of a novel Treg depleter RG6292, as a single agent and in combination with atezolizumab in patients with solid tumors [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 CT110.
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) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 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) | 0,002 | 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 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 ».