SC Pembrolizumab Noninferior to IV in NSCLC: Phase 3 Trial Results

Enriqueta Felip, MD, PhD, the Universitat Autònoma de Barcelona, Spain, section chief at the Vall d'Hebron University Hospital, head of the Vall d' Hebron Institute of Oncology's thoracic tumors group, discusses the results of the phase 3 3475A-D77 trial (NCT05722015) of subcutaneous (SC) pembrolizumab vs intravenous (IV) pembrolizumab, plus chemotherapy, for the treatment of metastatic non–small cell lung cancer (NSCLC).¹

Noninferior pharmacokinetics were observed when SC pembrolizumab was given with chemotherapy with a median injection time of 2 minutes vs IV pembrolizumab and chemotherapy for the first-line treatment of adult patients with metastatic NSCLC. Specifically, when SC pembrolizumab was given to patients every 6 weeks with a median injection time of 2 minutes (4.8 mL) plus chemotherapy, noninferiority of area under the curve (AUC) exposure of pembrolizumab during the first dosing cycle was observed, with a geometric mean ratio of 1.14 (96% CI, 1.06-1.22; P <.0001). Looking at trough concentration (Ctrough), the geometric mean ratio was 1.67 (94% CI, 1.52-1.84; P <.0001) at steady state, vs IV pembrolizumab administered every 6 weeks with chemotherapy.

“The study is positive for the 2 primary end points,” explains Felip. “ I think it's important also to analyze in the trial the secondary end points that are efficacy”

Looking at the secondary end points of the study, the objective response rate (ORR) was 45.4% (95% CI, 39.1%-51.8%) with SC pembrolizumab compared with 42.1% (95% CI, 33.3%-51.2%) for IV pembrolizumab (95% CI, 0.85-1.37). The median duration of response (DOR) was 9.1 months (95% CI, 6.9-not reached) with SC pembrolizumab vs 8.0 months (95% CI, 7.4-not reached) with IV pembrolizumab. Further, the median progression-free survival (PFS) was 8.1 months (95% CI, 6.3-8.3) vs 7.8 months (95% CI, 6.2-9.7; HR, 1.05; 95% CI, 0.78-1.43), and the median overall survival (OS) was not reached in either arm (HR, 0.81; 95% CI, 0.53-1.22).

The safety profiles of SC and IV pembrolizumab were also consistent. There were similar rates of grade 3 or greater adverse events (AEs) seen in both arms of the study (47% for SC vs 47.6% for IV).

Reference:

1. Felip E, Rojas CI, Schenker M, et al. Subcutaneous Versus Intravenous Pembrolizumab, in Combination With Chemotherapy, for Treatment of Metastatic Non-Small Cell Lung Cancer: The Phase 3 3475A-D77 Trial. Ann Oncol. Published online March 25, 2025. doi:10.1016/j.annonc.2025.03.012