Abstract CT133: A phase 1b multicenter study of anti-TIM3 (S095018/Sym023) in combination with anti-PD1 (Sym021) in patients with advanced/metastatic recurrent biliary tract cancer
Notice bibliographique
Résumé
Abstract Background: TIM3 is an inhibitory immunoreceptor linked to decreased activity of immune cells in the tumor microenvironment. S095018 is a human anti-TIM3 IgG2 antibody which blocks binding of phosphatidyl serine to TIM3 promoting the stimulation of T-cells, dendritic cells (DCs) and macrophages. Sym021 is a humanized IgG1 antibody that inhibits binding of PD-1 with its ligands PD-L1 and PD-L2. Preclinical data demonstrated that Sym021 combined with S095018 results in enhanced immunostimulatory antitumor activity. Methods: S095018 in combination with Sym021 was tested in patients with advanced/metastatic biliary tract cancer whose disease progressed under treatment with at least one line of systemic therapy and who had not received prior treatment with PD-1/-L1 inhibitors (NCT04641871). The dose/schedule of Sym021 and S095018 was 3mg/kg IV Q2W and 10mg/kg IV Q2W, respectively. Primary endpoints included overall response rate (ORR) using RECIST v1.1 and incidence/severity of adverse events. Key secondary endpoints included PK parameters, disease control rate (DCR), progression free survival (PFS) and overall survival (OS). Results As of 31-Oct-2023, 35 patients with stage IV biliary tract cancer (34 cholangiocarcinoma, 1 gallbladder adenocarcinoma) received S095018 in combination with Sym021. All patients were naïve to prior immune checkpoint inhibitor treatment. Twenty-two patients (62.9%) had received 1 prior antineoplastic systemic treatment for advanced/metastatic disease, 34.3% had received ≥2 prior treatments for advanced/metastatic disease. Overall, 34 patients (97.1%) discontinued treatment, 85.7% due to disease progression. Best overall response was 2 PR (5.7%), 11 SD (31.4%), 18 PD (51.4%) and 4 not evaluable. Median PFS and OS were 1.9 months (90% CI 1.8-3.7) and 13.4 months (90% CI 8.2-27.1) respectively. Disease control rate (CR+PR+SD) with SD≥16 weeks, ≥24 weeks and ≥12 months was 28.6%, 22.9% and 8.6% respectively. Treatment emergent adverse events of any grade occurring in >5% of patients included fatigue, pruritus, alkaline phosphatase increase, amylase increase, IRR (each 8.6%) and hypothyroidism, hyperthyroidism, AST increase, lipase increase and myalgia (each 5.7%). Exploratory biomarker analyses in paired tumor biopsies (N=18) showed an intratumoral increase in CD8 T-cell density, as well as upregulation of gene signatures related to IFNg signaling, antigen presentation, T-cell activation and cytotoxicity upon treatment. Baseline tumor biopsies from the two patients who achieved confirmed PR showed high PD-L1 expression. Conclusions: S095018 in combination with Sym021 exhibited antitumor activity in patients with advanced/metastatic recurrent biliary tract cancer who had not received prior treatment with PD-1/-L1 inhibitors. The combination was well tolerated without new safety signals. Further biomarker analysis is ongoing. Citation Format: Francois Ghiringhelli, Richard Kim, Teresa Macarulla, Irene Moreno, Albiruni Razak, Jordi Rodon, Chih-Yi Liao, Thomas Marron, Judith Raimbourg, Helene Kaplon, Julia Geromini, Najah Harouki, Christelle Rodrigues, Pauline Darcel, Niels Jorgen Skartved, Rikke Hald, Daleen Lopez-Ravnborg, Peng He, Xenophon Ianopoulos, Vasileios Askoxylakis, Nehal J. Lakhani, Sarah Davis, Amit Mahipal. A phase 1b multicenter study of anti-TIM3 (S095018/Sym023) in combination with anti-PD1 (Sym021) in patients with advanced/metastatic recurrent biliary tract cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT133.
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 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,002 | 0,001 |
| Méta-épidémiologie (sens large) | 0,002 | 0,001 |
| Bibliométrie | 0,001 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,001 |
| Communication savante | 0,001 | 0,001 |
| Science ouverte | 0,001 | 0,000 |
| Intégrité de la recherche | 0,001 | 0,003 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,005 | 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 ».