Abstract CT011: Penpulimab versus placebo in combination with chemotherapy as first-line treatment for recurrent or metastatic nasopharyngeal carcinoma: A global, multicenter, randomized, double-blind, phase 3 trial (AK105-304)
Notice bibliographique
Résumé
Abstract Background: Studies have shown that the combination of PD-1 inhibitors with chemotherapy exhibits promising efficacy as a first-line treatment for Asian patients with recurrent or metastatic nasopharyngeal carcinoma (R/M NPC). This presentation reports the results of a global phase 3 clinical trial with ethnically diverse patients treated with penpulimab plus chemotherapy vs. placebo plus chemotherapy as the first-line therapy for R/M NPC (NCT04974398). Methods: AK105-304 trial was conducted across 46 sites worldwide. Participants aged 18-75 years with previously non-systemically treated R/M NPC, stratified by disease stages (de novo metastases vs. recurrent), ECOG (0 vs. 1), liver metastasis (present vs. absent), were randomized (1:1) to receive penpulimab or placebo (200mg, Day1) in combination with gemcitabine (1000mg/m2, Day 1 and 8) and cisplatin (80mg/m2, Day1) or carboplatin (AUC5, Day1) every 3 weeks (Q3W) for up to 6 cycles, followed by maintenance therapy with penpulimab or placebo (200mg, Q3W). Placebo-arm patients were allowed to crossover to receive penpulimab monotherapy (200 mg, Q3W) upon confirmed disease progression by blinded independent center review (BICR). Primary endpoint was PFS assessed by BICR, and key secondary endpoint was OS. Other secondary endpoints included ORR, DoR and safety. Results: 291 patients were randomized to penpulimab arm (n=144) or placebo arm (n=147). Baseline characteristics were generally balanced between treatment arms. By April 29, 2024, median follow-up time was 19.1 months. Per BICR assessment, median PFS was 9.6 months (95% CI: 7.1, 12.5) and 7.0 months (95% CI: 6.9, 7.3), respectively, for penpulimab+chemo and placebo+chemo (HR=0.45, 95% CI: 0.33, 0.62, two-sided P < 0.0001). Confirmed ORR was 68.1% vs. 63.9%, and median DoR was 9.8 months (95% CI: 7.0, 17.5) vs. 5.7 months (95% CI: 5.5, 6.7) (HR=0.4, 95%CI: 0.27, 0.59). OS was not mature, with 48 deaths in penpulimab arm and 49 in placebo arm (HR=0.94, 95% CI: 0.63, 1.40). After adjusting for crossover of patients from placebo to penpulimab upon PD, OS benefit became more evident, with HR of 0.62 (0.41, 0.94) by Rank Preserving Structural Failure Time (RPSFT) model, 0.75 (0.43, 1.30) by Inverse Probability of Censoring Weighting (IPCW) method, and 0.78 (0.52, 1.17) by two-stage Accelerated Failure Time (AFT) model. The incidence of Grade ≥3 TRAEs was 89.0% vs. 85.9%; SAEs was 50.7% vs. 48.6%; irAEs was 30.8% vs. 8.5%; Grade ≥3 irAEs was 4.1% vs. 0. Conclusions: Penpulimab combined with gemcitabine and cisplatin or carboplatin demonstrated statistically significant and clinically meaningful benefit with a manageable safety profile, and provides a new beneficial treatment option in the first-line treatment for R/M NPC patients globally. Citation Format: Chaosu Hu, Xiaozhong Chen, Tingting Xu, Shuang Huang, Feng Liu, Song Qu, Lisha Chen, Ping Zhou, Shenhong Qu, Xiaohong Ai, Yong Chen, Meilian Liu, Rensheng Wang, Kelvin KW Chan, Peng Zhang, Chunhong Hu, Jiyu Wen, Jian Zhang, Qin Lin, Xiaojiang Li, Kangsheng Gu, Li Xiang, Dongxia Wang, Jingao Li, Daren Lin, Desheng Hu, Jianwu Ding, Siyang Wang, Xiaoming Huang, Lin Wang, Feng Jin, David G. Pfister, Milena Perez Mak, Pedro Rafael Martins de Marchi, Yi Jiang, Haihua Yang, Xiaoye Hu, Tianrun Liu, Dehua Wu, Aditya Shreenivas, Thiago Bueno de Oliveira, Carlos Eduardo Baston Silva, Gustavo Vasconcelos Alves, Xianming Li, Zhifang Yao, Dongmei Lu, Mingxiu Hu, Zhongmin Maxwell Wang, Baiyong Li, Michelle Xia. Penpulimab versus placebo in combination with chemotherapy as first-line treatment for recurrent or metastatic nasopharyngeal carcinoma: A global, multicenter, randomized, double-blind, phase 3 trial (AK105-304) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr CT011.
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) | 0,003 | 0,002 |
| Bibliométrie | 0,000 | 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 | 0,002 | 0,003 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,010 | 0,002 |
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 ».