Abstract CT302: Phase Ia/Ib dose-escalation study of the anti-TIGIT antibody tiragolumab as a single agent and in combination with atezolizumab in patients with advanced solid tumors
Notice bibliographique
Résumé
Abstract Background: The immunomodulatory receptor TIGIT (T-cell Immunoreceptor with Ig and ITIM domains) is a novel inhibitory immune checkpoint present on activated T cells and NK cells in multiple cancers. In preclinical models, co-inhibition of the TIGIT and PD-L1/PD-1 pathways improved anti-tumor activity compared to either agent alone. Tiragolumab (tira or MTIG7192A) is a humanized IgG1/kappa monoclonal antibody (mAb) that binds TIGIT to prevent its interaction with its ligand PVR (CD155). In this first-in-human dose-escalation study, we report the preliminary safety and anti-tumor activity of tira as a single agent and in combination with atezolizumab (atezo) in patients with advanced solid tumors. Methods: Enrolled patients, ECOG PS 0-1, had advanced tumors for whom standard therapy did not exist or was ineffective. Patients received escalating doses of tira alone IV Q3W alone (Phase Ia) or in combination with atezo 1200 mg IV Q3W (Phase Ib) to determine the maximum tolerated dose (MTD) and continued until disease progression, intolerable toxicity, or patient/investigator decision. Study objectives included evaluation of safety and tolerability, pharmacokinetics (PK), pharmacodynamics, and anti-tumor activity of tira alone or tira + atezo. Data cut-off date was April 2019. Results: 73 patients with multiple tumor types were treated in dose-escalation (24 in Phase Ia, 49 in Ib with tira + atezo). In Phase Ia and Phase Ib, median age was 60 and 54 years, ECOG 0 for 29% and 27% of patients, and those who received ≥ 3 prior therapies were 67% and 57%, respectively. No DLTs were observed. Across doses, treatment-related AEs occurred in 67% in Phase Ia and 59% in Phase Ib (Grade ≥ 3: 4% and 4%, respectively), and most common AEs were fatigue (38%) in Phase Ia and anemia (31%) in Phase Ib. Exposure of tira increased with increasing dose, and saturation of nonlinear PK occurred at tira doses ≥ 100 mg Q3W. Complete and sustained occupancy of peripheral TIGIT receptors was observed at tira doses ≥ 30 mg Q3W. In Phase Ia, there were no objective responses, but SD of > 4 months duration was observed (n=4). In Phase Ib, there were 3 responses, which all occurred in PD-L1 positive tumors (2 non-small cell lung cancer [NSCLC]: 1 CR, 1 PR; and 1 head/neck squamous cell carcinoma: PR) with two patients not receiving prior immunotherapy (CIT-naïve). Therefore, expansion cohorts were initiated in PD-L1-positive CIT-naïve indications in Phase Ib. In the metastatic NSCLC expansion cohort (n=14) ORR was 50%, with 1 CR and 6 PRs; DCR was 79%, and the safety profile was similar. Conclusions: Tira monotherapy or combined with atezo was well-tolerated and had an acceptable safety profile across all dose levels. Preliminary anti-tumor activity was observed in Phase Ib with tira + atezo in CIT-naïve PD-L1-positive tumors, including NSCLC, and enrollment is ongoing in these expansion cohorts. Citation Format: Johanna C. Bendell, Philippe Bedard, Yung-Jue Bang, Patricia LoRusso, Stephen Hodi, Michael Gordon, Sandra D'Angelo, Sandra D'Angelo, Jayesh Desai, Elena Garralda, Antoine Italiano, Myung-Ju Ahn, Andres Cervantes, Zev Wainberg, Emiliano Calvo, Marta Gil-Martin, Maria Martinez-Garcia, Rastilav Bahleda, Philippe Cassier, Jean-Pierre Delord, Amy Prawira, Ignacio Melero, Leisha Emens, Emanuela Romano, Karen Miller, Robert W. Hsieh, Cloris Xue, Kari Morrissey, Patrick Twomey, Kelly Gash, Namrata S. Patil, Jane Grogan, Raymond Meng, Byoung Cho, Tae Won Kim. Phase Ia/Ib dose-escalation study of the anti-TIGIT antibody tiragolumab as a single agent and in combination with atezolizumab in patients with advanced solid tumors [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT302.
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 | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 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 ».