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
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Elsevier
Abstract
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 %single bond64 %; 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.
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Keywords
Anti–PD-1, Immunotherapy, Pembrolizumab
Sustainable Development Goals
SDG-03: Good health and well-being
Citation
Cohen, G.L., Coetzee, C., Walton, C.A. et al. 2025, 'Pharmacokinetics and bioavailability of pembrolizumab with berahyaluronidase alfa for subcutaneous administration in participants with advanced or metastatic solid tumors', European Journal of Cancer, vol. 230, art. 115709, pp. 1-9. https://doi.org/10.1016/j.ejca.2025.115709.