Abstract C027: A Phase I, dose finding study of BI 754111, an anti-LAG-3 antibody, in combination with BI 754091, an anti-PD-1 antibody, in patients with advanced solid tumors: preliminary results from the microsatellite stable (MSS) metastatic colorectal cancer (mCRC) cohort
Notice bibliographique
Résumé
Abstract Background: Inhibition of the PD-1 pathway is an effective immunotherapeutic approach in a subset of patients with various solid tumors and hematologic malignancies. Blockade of the PD-1 pathway leads to overexpression of other checkpoint receptors, including LAG3, potentially providing an escape pathway for tumor cells. LAG-3 signaling contributes to immune cell exhaustion, preventing T-cell proliferation. Dual blockade of PD-1 and LAG-3 has the potential to synergistically restore T-cell functionality and therefore enhance antitumor immune responses. This Phase I trial is evaluating the combination of BI 754111, an anti-LAG-3 monoclonal antibody (mAb), and BI 754091, an anti-PD-1 mAb, in patients with advanced solid tumors. Methods: This open-label, Phase I study is being conducted in two parts. Part 1 (dose-escalation) enrolled patients with advanced solid tumors; no dose limiting toxicities were reported and BI 754111 600 mg intravenous (iv) every 3 weeks (q3w) in combination with BI 754091 (240 mg iv q3w) was selected for further assessment in part 2 (dose expansion). In part 2, patients are being enrolled in 4 cohorts: 1) anti-PD-(L)1 pretreated non-small cell lung cancer (NSCLC) that progressed after having achieved benefit on previous PD-(L)1; 2) previously treated (anti-PD-[L]1 naïve) MSS mCRC; 3) anti-PD-(L)1 pretreated TMB >10 and/or MSI-h and/or dMMR solid tumors; 4) treatment-naive NSCLC with EGFR and ALK wild type tumors. Primary endpoint for the expansion cohorts is objective response. Safety and pharmacokinetics of the combination were secondary endpoints. The mCRC cohort is fully recruited; other cohorts are open to recruitment. This abstract presents data from the MSS CRC cohort. Results. 40 patients with MSS mCRC were enrolled (27 male [67.5%]; median age 56.5 years [range 25–85]; median of 3.0 prior regimens [range 1–10]) and received BI 754111 600 mg q3w in combination with BI 754091 240 mg q3w. Treatment-related AEs (TRAEs) were reported in 18 patients (45%); most commonly infusion-related reactions (10.0%), myalgia (10.0%), hypothyroidism (7.5%), diarrhea (7.5%) and arthralgia (7.5%). Grade 3/4 TRAEs occurred in 4 patients (grade 3 colitis, grade 3 maculo-papular rash, grade 4 diabetic ketoacidosis [n=2]). Treatment-emergent immune-related AEs occurred in 9 patients; of these, 4 had grade 3/4 events (colitis and maculo-papular rash [grade 3] and diabetic ketoacidosis [grade 4; n=2]). To date, 2 (5%) patients achieved a partial response, and 12 (30%) achieved stable disease. Updates will be presented. Conclusion. BI 754111 + BI 754091 was well-tolerated and showed preliminary activity in patients with previously treated MSS mCRC. Assessment of the combination in other cohorts is ongoing. Citation Format: Johanna Bendell, Susanna V Ulahannan, Quincy Chu, Manish Patel, Ben George, Renee Landsberg, Mabrouk Elgadi, Christine Duffy, Ralph Graeser, Wenbo Tang, Michael Merger, Miaomiao Ge, Melissa Johnson. A Phase I, dose finding study of BI 754111, an anti-LAG-3 antibody, in combination with BI 754091, an anti-PD-1 antibody, in patients with advanced solid tumors: preliminary results from the microsatellite stable (MSS) metastatic colorectal cancer (mCRC) cohort [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2019 Oct 26-30; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2019;18(12 Suppl):Abstract nr C027. doi:10.1158/1535-7163.TARG-19-C027
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) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,000 | 0,001 |
| 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 | 0,000 |
| 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 ».