| 論文種別 | 原著(症例報告除く) |
| 言語種別 | 英語 |
| 査読の有無 | その他(不明) |
| 表題 | Pharmacokinetics and bioavailability of pembrolizumab with berahyaluronidase alfa for subcutaneous administration in participants with advanced or metastatic solid tumors: The phase 1 study 3475A-C18. |
| 掲載誌名 | 正式名：European journal of cancer (Oxford, England : 1990) 略 称：Eur J Cancer ISSNコード：18790852/09598049 |
| 掲載区分 | 国外 |
| 巻・号・頁 | 230,pp.115709 |
| 著者・共著者 | Graham L Cohen, Corlia Coetzee, Cathryn A Walton, Òscar Reig Torras, Byoung Chul Cho, Georgina McAdam, Carlos I Rojas, Laura Medina Rodríguez, Zsuzsanna Papai, Sze W Chan, Bernardo L Rapoport, Christian Caglevic, Patricio Yañez Weber, Toshiaki Takahashi, Takayasu Kurata, Gina Song, Julia W Cohen, Omobolaji O Akala, Richard Khanyile |
| 発行年月 | 2025/11 |
| 概要 | BACKGROUND:MK-3475A is pembrolizumab with berahyaluronidase alfa for subcutaneous administration (pembrolizumab SC). The phase 1 study 3475A-C18 (NCT05017012) assessed the pharmacokinetic and safety profiles of pembrolizumab SC.METHODS:The study had 4 arms that enrolled participants with unresectable or advanced melanoma (arms 1, 2, and 4), metastatic NSCLC (arms 1-3), or advanced or metastatic RCC (arms 1 and 2). Participants received pembrolizumab SC 650 mg Q6W at solution strengths of 165 mg/mL (arms 1 and 3), 130 mg/mL (arm 2), or pembrolizumab SC 395 mg Q3W at 165 mg/mL (arm 4). Key endpoints included pembrolizumab SC bioavailability, pharmacokinetics, immunogenicity, and safety and tolerability.RESULTS:140 participants received study treatment. Across all arms, mean bioavailability of pembrolizumab SC was 61 % (95 % CI, 58 %64 %; CV%, 22.4 %) and absorption rate was 0.30/day (95 % CI, 0.28-0.32/day; CV%, 43.7 %). Pharmacokinetic exposure, bioavailability, and absorption rate did not differ meaningfully with pembrolizumab SC by solution strength. Treatment-emergent anti-drug antibodies against pembrolizumab and berahyaluronidase occurred in 1 % and 2 % of participants, respectively. Injection site AEs with pembrolizumab SC occurred in 16 % of participants; all were grade 1/2 in severity. Immune-mediated AEs occurred in 41 % of participants in arms 1-3 and 18 % of participants in arm 4.CONCLUSION:Results from study 3475A-C18 informed selection of pembrolizumab SC 790 mg Q6W at 165 mg/mL for further clinical development to ensure that all patients have the appropriate pembrolizumab exposure to derive expected clinical benefit. Arm 4 results provided key clinical data supporting the pembrolizumab SC 395 mg Q3W dosing regimen.TRIAL REGISTRATION:ClinicalTrials.gov, NCT05017012. |
| DOI | 10.1016/j.ejca.2025.115709 |
| PMID | 40957773 |