Pembrolizumab subcutaneous

Over the last decade, pembrolizumab has become a very important agent in the treatment arsenal for patients with non-small cell lung cancer (NSCLC). However, the intravenous route of administration of this agent does bring about a certain treatment burden. To mitigate this, a subcutaneous formulation of pembrolizumab has been developed. In this video, Prof Mariana Brandão, medical oncologist at the Institut Jules Bordet In Brussels, discusses the results of a phase 3, non-inferiority study presented at ELCC 2025 in which this subcutaneous (SC) formulation of pembrolizumab was compared to the classical intravenous (IV) formulation.

The phase 3 MK-3475A-D77 trial randomly assigned 377 newly diagnosed, stage IV, NSCLC patients without an oncogenic driver mutation to receive pembrolizumab SC (790 mg every 6 weeks for up to 18 cycles) or IV (at 400 mg every 6 weeks for up to 18 cycles). The dual primary endpoints of the study were cycle 1 pembrolizumab exposure (area under the curve from weeks 0-6; AUC0-6wk) and steady-state trough concentration (Ctrough), expressed as geometric mean ratios (GMRs). The GMR for cycle 1 AUC0-6wk was 1.14, while the GMR for steady-state Ctrough was  reported at 1.67, both within the statistical margins for non-inferiority. Importantly, the trial also showed an equivalent result with both formulations in terms of efficacy and safety. Injection-site reactions were only reported in 2.4% of patients receiving SC pembrolizumab (all grade 1).

The median injection time for pembrolizumab SC was 2 minutes for a volume of 4.8 mL, which is shorter than what is achieved with SC atezolizumab. Later this year, further data with pembrolizumab SC will be presented that will provide information on dose finding and provide insights into patient preferences.

Based on these results, Prof Brandão is convinced that, once reimbursed, this easier to use pembrolizumab formulation will rapidly be adopted. The latter will especially be the case in patients who receive pembrolizumab as monotherapy.