Abstract P3-07-04: A multicenter, single-arm, open-label Phase I study of AN1004 (Pelareorep) oncolytic virus plus paclitaxel in Chinese patients with Hormone receptor-positive and HER2-negative advanced/metastatic breast cancer (REO 026-1)
Notice bibliographique
Résumé
Abstract A multicenter, single-arm, open-label Phase I study of AN1004 (Pelareorep) oncolytic virus plus paclitaxel in Chinese patients with Hormone receptor-positive and HER2-negative advanced/metastatic breast cancer (REO 026-1) Background: AN1004, also known as Pelareorep is an intravenously delivered immuno-oncolytic unmodified reovirus being evaluated to treat multiple malignancies. AN1004 was shown to be safe and well-tolerated in both monotherapy and combination therapy in multiple clinical trials in North American and European populations, including two completed and two ongoing breast cancer studies. The completed phase 2 study (NCT01656538) in advanced/metastatic breast cancer demonstrated improved median overall survival (OS) in Canadian patients treated with AN1004 plus paclitaxel (PTX) versus PTX alone, and the greatest benefit in OS was observed in patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) subtype. Since there has been no clinical trial assessing AN1004 in Chinese population, a bridging study (REO 026-1) was initiated to evaluate its safety and tolerability in combination with PTX in Chinese patients with HR+/HER2- advanced/metastatic breast cancer. Methods: Eligible Chinese patients must be female with good performance status (ECOG PS: 0 or 1), have had histopathological diagnosis with HR+/HER2- advanced/metastatic breast cancer, and were previously treated with at least one endocrine therapy with no more than one line of chemotherapy regimen for recurrent/metastatic disease. Patients are intravenously infused with AN1004 at escalating dose levels of 1.5 × 10^10 (Dose Level 1, DL1 group), 3 × 10^10 (DL2 group) and 4.5 × 10^10 TCID50 (DL3 group) on days 1, 2, 8, 9, 15, and 16 every 28 days plus PTX 80 mg/m^2 intravenously on days 1, 8, and 15 every 28 days. Three to six patients will be enrolled in the DL1 group, and 6 patients will be enrolled in each of the DL2 and DL3 groups. The primary objective is to assess the safety and tolerability of AN1004 in combination with PTX. A secondary objective is to evaluate the preliminary activity of AN1004 and PTX combination therapy. Results: By the data cutoff date of June 2nd, 2022, a total of 10 female patients were enrolled, with a median age of 58 years (range 36-67). Two (20%) patients had failed more than one prior line of endocrine therapy for advanced/metastatic disease, and 3 (30%) patients were previously treated with a CDK4/6 inhibitor. Three patients were treated with AN1004 and PTX in DL1 group; six patients were treated in DL2 group; one patient was treated in DL3 group. The most common (>50%, and/or liver function related) treatment emergent adverse events (TEAEs) included neutrophil count decreased and white blood cell count decreased (90% each), hypertriglyceridemia (70%), pyrexia, ALT increased and anemia (60% each), and AST increased (40%). Three (30%) patients had Grade 3 or above TEAEs, including neutrophil count decreased (30%), white blood cell count decreased (20%), hypertriglyceridemia, ALT increased and GGT increased (10% each). No serious AE or AE leading to treatment discontinuation was reported to date. One patient was not evaluable for dose-limiting toxicity (DLT) due to early withdrawal, and there were no DLTs observed in the 9 evaluable patients. Among the 10 treated patients, 2 (20%) patients achieved confirmed partial response (PR), 2 (20%) patients achieved unconfirmed PR, and 5 (50%) patients showed stable disease (SD). One patient in DL1 group achieved a confirmed PR and later progressed, and the other 8 patients who had PR or SD continue to receive treatment as of the data cut. Conclusion: To date, intravenous administration of AN1004 plus PTX is safe and well-tolerated in Chinese patients with advanced/metastatic breast cancer, and demonstrates anti-tumor activity. Citation Format: Wei Li, Yongmei Yin, Jiuwei Cui, Wenna Wang, Yan Liang, Hongming Liang, Binghe Xu. A multicenter, single-arm, open-label Phase I study of AN1004 (Pelareorep) oncolytic virus plus paclitaxel in Chinese patients with Hormone receptor-positive and HER2-negative advanced/metastatic breast cancer (REO 026-1) [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-07-04.
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 | 0,002 | 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 | 0,001 | 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) | 0,004 | 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 ».