Trial results for a study investigating a subcutaneous (SC) formulation of pembrolizumab (coformulated with berahyaluronidase alfa) against intravenous (IV) pembrolizumab in adult Japanese participants with metastatic non-small cell lung cancer (NSCLC) were posted on ClinicalTrials.gov on 2025-11-12. The study found a Geometric Mean Ratio (GMR) of 1.1 (95% CI: 0.95 to 1.27) for a key pharmacokinetic parameter, supporting the primary hypothesis of noninferiority for PK.
Background
The study, titled 'A Study of Subcutaneous (SC) Pembrolizumab Coformulated With Berahyaluronidase Alfa (MK-3475A) vs Intravenous Pembrolizumab in Adult Participants With Metastatic Non-small Cell Lung Cancer (NSCLC) (MK-3475A-D77)-Japan Extension,' aimed to assess the pharmacokinetics (PK) and safety of the subcutaneous (SC) formulation of pembrolizumab with chemotherapy in first-line treatment of adult Japanese participants with metastatic non-small cell lung cancer.
Trial design
The Phase 3 study (NCT06212752) enrolled 39 adult Japanese participants with metastatic non-small cell lung cancer (NSCLC). It compared subcutaneous pembrolizumab coformulated with berahyaluronidase alfa plus platinum doublet chemotherapy (Arm 1) against intravenous pembrolizumab plus platinum doublet chemotherapy (Arm 2). The primary hypotheses focused on the noninferiority of the SC formulation's pharmacokinetic (PK) parameters compared to the IV formulation.
Key results
The trial results included several pharmacokinetic (PK) and efficacy measurements. Key analyses for pharmacokinetic parameters showed a Geometric Mean Ratio (GMR) of 1.1 (95.0% CI: 0.95 to 1.27) and another GMR of 1.46 (95.0% CI: 1.14 to 1.88). Individual PK measurements for Arm 1 (SC) vs Arm 2 (IV) included:
- Cycle 1 Area Under the Curve From Time 0 to 6 Weeks (AUC0-6 Weeks): 1864.76 µg·day/mL (Geometric Coefficient of Variation: 22.18) vs 1697.98 µg·day/mL (Geometric Coefficient of Variation: 18.50).
- Cycle 3 Trough Serum Concentration (Ctrough) at Steady State: 45.11 µg/ml (Geometric Coefficient of Variation: 35.58) vs 30.86 µg/ml (Geometric Coefficient of Variation: 24.93).
- Cycle 1 Maximum Serum Concentration (Cmax) After the First Dose: 71.54 µg/ml (Geometric Coefficient of Variation: 23.7) vs 141.9 µg/ml (Geometric Coefficient of Variation: 16.4).
- Cycle 1 Trough Serum Concentration (Ctrough) After the First Dose: 23.62 µg/ml (Geometric Coefficient of Variation: 27.9) vs 16.27 µg/ml (Geometric Coefficient of Variation: 29.7).
- Cycle 3 Area Under the Curve From Time 0 to 6 Weeks (AUC0-6 Weeks) at Steady State: 3116 µg•day/ml (Geometric Coefficient of Variation: 27.3) vs 2514 µg•day/ml (Geometric Coefficient of Variation: 17.3).
For efficacy, the Objective Response Rate (ORR) was 64.3% (Percentage of participants) for Arm 1 (SC) and 18.2% (Percentage of participants) for Arm 2 (IV).
What this means
The pharmacokinetic data, including the Geometric Mean Ratios, suggest that the subcutaneous formulation of pembrolizumab demonstrates PK parameters comparable to or higher than the intravenous formulation, supporting the noninferiority hypothesis. The numerically higher Objective Response Rate (ORR) for the subcutaneous arm is also notable. These findings could offer a more convenient administration option for pembrolizumab in patients with metastatic NSCLC, while maintaining comparable drug exposure.
Source
The information for these trial results was sourced from ClinicalTrials.gov, a public database of clinical studies. The results for study NCT06212752, titled 'A Study of Subcutaneous (SC) Pembrolizumab Coformulated With Berahyaluronidase Alfa (MK-3475A) vs Intravenous Pembrolizumab in Adult Participants With Metastatic Non-small Cell Lung Cancer (NSCLC) (MK-3475A-D77)-Japan Extension,' were posted on 2025-11-12 on clinicaltrials.gov.