Most Patients Prefer SC Over IV Pembrolizumab, Phase 2 Data Show

Nearly two-thirds of patients preferred subcutaneous (SC) pembrolizumab with berahyaluronidase alfa (Keytruda Qlex) over the intravenous (IV) formulation (Keytruda) after experiencing both administration routes, according to results of a randomized, open-label phase 2 crossover study (NCT06099782) published in JCO Oncology Practice.¹

Between 2023 and 2024, 147 adult patients with resected melanoma, resected renal cell carcinoma (RCC), and metastatic non–small cell lung cancer (NSCLC) across global sites were randomly assigned to receive pembrolizumab subcutaneously (n = 71) or intravenously (n = 76) for 3 cycles before crossing over to the other route for 3 cycles.²

Among 118 evaluable patients, the preference rate for pembrolizumab administered subcutaneously was 65% (95% CI, 56%-74%), as assessed by a patient preference questionnaire. The most common reason cited for the preference was less time spent in clinic, reported by 64% of patients.

Satisfaction data followed a similar pattern. Altogether, 64% and 25% of patients reported being very satisfied or satisfied, respectively, with SC pembrolizumab compared with 54% and 31% who reported being very satisfied or satisfied with the IV formulation. This preference also translated into treatment decisions beyond the questionnaire: more patients chose to continue treatment after cycle 6 with SC pembrolizumab than with IV (68% vs 32%).

Safety findings were consistent with the established profile of pembrolizumab, with a lower rate of grade 3 and 4 treatment-related adverse events (AEs) reported during the first 3 cycles in the arm that started with the SC formulation. Grade 3 and 4 treatment-related AEs during cycles 1 to 3 occurred in 1 patient (1%) in arm A and 5 participants (7%) in arm B. Injection-site reactions were reported during the SC administration cycles regardless of sequence: these events occurred in 9 patients (13%) in arm A and 11 patients (16%) in arm B and were mostly grade 1 in severity.

“The results of the study…support pembrolizumab SC as a cancer treatment that uses a more convenient, less time-consuming route of administration without compromising efficacy and safety relative to pembrolizumab IV,” study authors Casarini et al concluded.

Clinical Context

The FDA granted approval to SC pembrolizumab across all previously approved solid tumor indications for IV pembrolizumab in September 2025.³ These preference and satisfaction findings build on pharmacokinetic data from the phase 3 3475A-D77 trial (NCT05722015), which supported the approval and established noninferior pharmacokinetics of SC pembrolizumab to pembrolizumab IV, with comparable efficacy and safety when combined with platinum-doublet chemotherapy in patients with metastatic NSCLC.⁴

The time savings identified in the present study as the leading driver of patient preference may also carry operational implications for practices, including reduced chair time in infusion centers and potentially greater scheduling flexibility, although those considerations were not directly assessed in either trial. Taken together, the 2 trials support SC pembrolizumab as a potential alternative route of administration across tumor types.

REFERENCES

1. Casarini IA, Kowalski DM, Caglevic C, et al. Participant-Reported Preference for Pembrolizumab Administered Subcutaneously or Intravenously: A Randomized, Open-Label, Phase II Study. JCO Oncol Pract. Published online June 3, 2026. doi:10.1200/op-25-01248

2. A Study of Participant Reported Preference for Subcutaneous Pembrolizumab Coformulated With Berahyaluronidase Alfa (MK-3475A) Over Intravenous Pembrolizumab (MK-3475) Formulation in Multiple Tumor Types (MK-3475A-F11). ClinicalTrials.gov. Updated April 8, 2026. Accessed July 31, 2026. https://clinicaltrials.gov/study/NCT06099782

3. FDA approves pembrolizumab and berahyaluronidase alfa-pmph for subcutaneous injection. News release. US FDA. September 19, 2025. Accessed July 31, 2026. https://tinyurl.com/2n3rsmjz

4. Merck’s Investigational Subcutaneous Pembrolizumab With Berahyaluronidase Alfa Demonstrates Noninferior Pharmacokinetics Compared to Intravenous (IV) KEYTRUDA® (pembrolizumab) in Pivotal 3475A-D77 Trial. News release. Merck. Published March 27, 2025. Accessed July 31, 2026. https://tinyurl.com/43w723rj