Subcutaneous Versus Intravenous Pembrolizumab, in Combination With Chemotherapy, for Treatment of Metastatic Non-Small Cell Lung Cancer: The Phase 3 3475A-D77 Trial.

IF 56.7 1区医学 Q1 ONCOLOGY

Annals of Oncology Pub Date : 2025-03-25 DOI:10.1016/j.annonc.2025.03.012

E Felip, C I Rojas, M Schenker, D M Kowalski, I A Casarini, T Csöszi, M A N Şendur, J Martins, A C Blanco, C-C Wang, X Song, R A L Ramirez Fallas, H Yoshioka, S Nair, M Wang, X Deng, M Lala, R Eiras, T Takahashi

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引用次数: 0

Abstract

Background: Pembrolizumab with berahyaluronidase alfa is for subcutaneous (SC) administration. The phase 3 open-label 3475A-D77 study (NCT05722015) assessed SC pembrolizumab versus intravenous (IV) pembrolizumab, plus chemotherapy, for treatment of metastatic non-small-cell lung cancer (mNSCLC).

Participants and methods: Participants with newly diagnosed stage IV squamous or nonsquamous NSCLC without sensitizing EGFR, ALK, or ROS1 alterations were randomized 2:1 to pembrolizumab SC 790 mg every 6 weeks (Q6W) or pembrolizumab IV 400 mg Q6W (18 cycles), each given with platinum doublet chemotherapy. Dual primary endpoints were pharmacokinetics exposure measures of cycle 1 area-under-the-curve (AUC_0-6wks) and steady-state trough concentration (C_trough) of pembrolizumab. The noninferiority margin for AUC_0-6wks and C_trough geometric mean ratios (GMR) of pembrolizumab SC versus IV was specified as 0.8. Secondary endpoints included additional pharmacokinetics exposure measures, pembrolizumab immunogenicity, efficacy, and safety.

Results: 377 participants were randomized to the pembrolizumab SC (n=251) or IV (n=126) arms. Median time from randomization to data cutoff (12Jul2024) was 9.6 months (range 6.2-16.4). Median injection time for pembrolizumab SC was 2.0 minutes (range 1-12). The GMR (96% CI) for cycle 1 AUC_0-6wks was 1.14 (1.06-1.22); P<0.0001. The GMR (94% CI) for steady-state C_trough was 1.67 (1.52-1.84); P<0.0001. Secondary pharmacokinetics endpoints were within established bounds for pembrolizumab. Anti-pembrolizumab antibodies were detected in 1.4% (pembrolizumab SC arm) and 0.9% (pembrolizumab IV arm) of participants. For the pembrolizumab SC versus IV arms, objective response rates were 45.4% vs 42.1% (ORR ratio 1.08, 95% CI 0.85-1.37). Other efficacy measures were similar and safety profiles were consistent between treatment arms.

Conclusions: Overall exposure and trough concentrations of pembrolizumab SC 790 mg Q6W were noninferior to those of pembrolizumab IV 400 mg Q6W given with chemotherapy in participants with treatment-naïve mNSCLC. Results support pembrolizumab SC as a treatment option in all indications where pembrolizumab IV can be used.

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来源期刊

Annals of Oncology 医学-肿瘤学

CiteScore

63.90

自引率

1.00%

发文量

3712

审稿时长

2-3 weeks

期刊介绍： Annals of Oncology, the official journal of the European Society for Medical Oncology and the Japanese Society of Medical Oncology, offers rapid and efficient peer-reviewed publications on innovative cancer treatments and translational research in oncology and precision medicine. The journal primarily focuses on areas such as systemic anticancer therapy, with a specific emphasis on molecular targeted agents and new immune therapies. We also welcome randomized trials, including negative results, as well as top-level guidelines. Additionally, we encourage submissions in emerging fields that are crucial to personalized medicine, such as molecular pathology, bioinformatics, modern statistics, and biotechnologies. Manuscripts related to radiotherapy, surgery, and pediatrics will be considered if they demonstrate a clear interaction with any of the aforementioned fields or if they present groundbreaking findings. Our international editorial board comprises renowned experts who are leaders in their respective fields. Through Annals of Oncology, we strive to provide the most effective communication on the dynamic and ever-evolving global oncology landscape.