Abstract CT266: Chinese race and origin have no clinically meaningful effect on tiragolumab and atezolizumab pharmacokinetics and safety in patients with advanced solid tumors
Notice bibliographique
Résumé
Abstract Background: Tiragolumab is a fully human IgG1 monoclonal antibody targeting the immune checkpoint TIGIT and is under evaluation in combination with anti-PD-L1 (atezolizumab) therapy. Here we report PK, safety, and preliminary anti-tumor activity from a Phase I open-label study (YP42514, CTR20210219) evaluating tiragolumab + atezolizumab in Chinese patients (pts) with advanced or metastatic solid tumors. Methods: Pts ≥18 years of age with an ECOG performance status of 0 or 1, a life expectancy of ≥12 weeks, adequate hematologic and end organ function who were residents in mainland China were eligible. Pts received tiragolumab 600 mg + atezolizumab 1200 mg IV every 3 weeks. Serial PK sampling was obtained in the first dosing Cycle on Days 1, 2, 8, 15, and 21, followed by sparse peak and trough collection. PK parameters were assessed by noncompartmental analysis and summarized using descriptive statistics. The severity of adverse events (AEs) was assessed using NCI CTCAE v5. Confirmed overall response rate and duration of response (DOR) were determined by investigator. Data cutoff: Feb 10, 2022. To support the dosing approach, findings in the current study were compared with results of a global Phase I study GO30103 (NCT02794571) [Bendell JC, et al. Cancer Res 2020;80:(suppl 16; Abst CT302)] in pts from France, Korea, Spain, the United States, Canada, and Australia receiving the same combination and dosing regimen. Results: Twenty Chinese pts were enrolled and received a median of 5 doses of tiragolumab + atezolizumab. Pts had a median age of 57.5 (range 44-73) years, were mostly male (85%), had a median of ≥2 prior lines of therapy and 30% of pts received prior immunotherapy. Non-small cell lung cancer was the most common tumor type (55%). Exposures in Chinese pts were comparable to the global population, with a geometric mean ratio (GMR) of 1.07 for Cycle 1 tiragolumab area under the concentration-time curve from 0 to 21 days, and a GMR of 0.92 and 0.93 for Cycle 1 peak and trough atezolizumab exposure, respectively. The frequency of treatment-related AEs, all-cause grade 3/4 AEs, grade 3/4 AEs of special interest, and AEs leading to withdrawal from study treatment were generally similar for pts in China (85.0%, 40%, 10%, and 5.0%) and those in the global GO30103 study (71.3%, 41.7%, 5.3%, and 5.6%). Treatment exposure was similar in the YP42514 study vs the respective global GO30103 cohort. Two Chinese pts (10%) had a partial response, their DORs were 3 and 6 months (censored), and seven pts (35%) had stable disease. Conclusions: Tiragolumab + atezolizumab was tolerable with preliminary anti-tumor activity. No meaningful differences in the PK or safety profile of tiragolumab + atezolizumab were seen between Chinese and global populations. Citation Format: Colby Shemesh, Yongsheng Wang, Andrew An, Hao Ding, Phyllis Chan, Qi Liu, Yih-Wen Chen, Benjamin Wu, Qiong Wu, Xian Wang. Chinese race and origin have no clinically meaningful effect on tiragolumab and atezolizumab pharmacokinetics and safety in patients with advanced 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 CT266.
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) | 0,000 | 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 | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,008 | 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 ».