Trial results for a Phase 3 study (NCT05722015) evaluating subcutaneous (SC) pembrolizumab coformulated with berahyaluronidase alfa (MK-3475A) against intravenous (IV) pembrolizumab in adults with metastatic non-small cell lung cancer (NSCLC) were posted on ClinicalTrials.gov on 2025-07-28. The study's primary hypothesis was that the SC formulation would be noninferior to the IV formulation with respect to pharmacokinetic (PK) parameters, with key analyses showing geometric mean ratios (GMRs) of 1.14 and 1.67 for certain PK outcomes.
Background
The study investigated pembrolizumab, an immunotherapy drug, for the treatment of metastatic non-small cell lung cancer (NSCLC). This trial specifically compared a novel subcutaneous (SC) formulation of pembrolizumab, coformulated with berahyaluronidase alfa (MK-3475A), against the established intravenous (IV) administration.
Trial design
The Phase 3 study, NCT05722015, 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)", enrolled 377 adult participants. The trial investigated the pharmacokinetics (PK) and safety of SC pembrolizumab formulated with berahyaluronidase alfa (MK-3475A) versus intravenous (IV) pembrolizumab (MK-3475), administered with chemotherapy in the first-line treatment of metastatic non-small cell lung cancer. The primary hypotheses focused on demonstrating noninferiority of the SC formulation to the IV formulation with respect to PK parameters.
Key results
Key pharmacokinetic results were reported for both the subcutaneous and intravenous formulations:
For Cycle 1: Area Under the Curve From Time 0 to 6 Weeks (AUC0-6 Weeks) of Pembrolizumab After the First Dose:
- Arm 1 (SC Pembrolizumab + Platinum Doublet Chemotherapy): Geometric Mean of 1633.24 μg·day/mL (Geometric Coefficient of Variation: 40.41)
- Arm 2 (IV Pembrolizumab + Platinum Doublet Chemotherapy): Geometric Mean of 1437.58 μg·day/mL (Geometric Coefficient of Variation: 26.23)
For Cycle 3: Trough Serum Concentration (Ctrough) of Pembrolizumab at Steady State:
- Arm 1 (SC Pembrolizumab + Platinum Doublet Chemotherapy): Geometric Mean of 39.23 μg/mL (Geometric Coefficient of Variation: 43.29)
- Arm 2 (IV Pembrolizumab + Platinum Doublet Chemotherapy): Geometric Mean of 23.49 μg/mL (Geometric Coefficient of Variation: 44.23)
For Cycle 1: Maximum Serum Concentration (Cmax) of Pembrolizumab After the First Dose:
- Arm 1 (SC Pembrolizumab + Platinum Doublet Chemotherapy): Geometric Mean of 64.88 μg/mL (Geometric Coefficient of Variation: 44)
- Arm 2 (IV Pembrolizumab + Platinum Doublet Chemotherapy): Geometric Mean of 129.7 μg/mL (Geometric Coefficient of Variation: 20.8)
For Cycle 1: Trough Serum Concentration (Ctrough) of Pembrolizumab After the First Dose:
- Arm 1 (SC Pembrolizumab + Platinum Doublet Chemotherapy): Geometric Mean of 19.36 μg/mL (Geometric Coefficient of Variation: 52.2)
- Arm 2 (IV Pembrolizumab + Platinum Doublet Chemotherapy): Geometric Mean of 12.26 μg/mL (Geometric Coefficient of Variation: 50.8)
For Cycle 3: Area Under the Curve From Time 0 to 6 Weeks (AUC0-6 Weeks) of Pembrolizumab at Steady State:
- Arm 1 (SC Pembrolizumab + Platinum Doublet Chemotherapy): Geometric Mean of 2798 μg·day/mL (Geometric Coefficient of Variation: 35.5)
- Arm 2 (IV Pembrolizumab + Platinum Doublet Chemotherapy): Geometric Mean of 2122 μg·day/mL (Geometric Coefficient of Variation: 27.8)
For Cycle 3: Maximum Serum Concentration (Cmax) of Pembrolizumab at Steady State:
- Arm 1 (SC Pembrolizumab + Platinum Doublet Chemotherapy): Geometric Mean of 98.96 μg/mL (Geometric Coefficient of Variation: 36.8)
- Arm 2 (IV Pembrolizumab + Platinum Doublet Chemotherapy): Geometric Mean of 148 μg/mL (Geometric Coefficient of Variation: 21.6)
Key analyses of the pharmacokinetic parameters included:
- A Geometric Mean Ratio (GMR) of 1.14 (96.0% CI: 1.06 to 1.22) with a p-value of 1e-05, calculated using Welch's t-test.
- A GMR of 1.67 (94.0% CI: 1.52 to 1.84) with a p-value of 1e-05, calculated using Welch's t-test.
What this means
The pharmacokinetic results suggest that the subcutaneous formulation of pembrolizumab, when coformulated with berahyaluronidase alfa, achieves comparable or higher systemic exposure compared to the intravenous formulation in patients with metastatic non-small cell lung cancer. Specifically, the SC formulation demonstrated higher geometric mean values for Area Under the Curve (AUC) at both Cycle 1 and Cycle 3, and for Trough Serum Concentration (Ctrough) at Cycle 1 and Cycle 3, compared to the IV formulation. While the Maximum Serum Concentration (Cmax) was lower for the SC formulation, the overall exposure (AUC) and steady-state trough levels were maintained or increased, supporting the trial's primary hypothesis of noninferiority for PK parameters. These findings could potentially offer a more convenient administration option for patients, reducing clinic time associated with intravenous infusions.
Source
The information regarding these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for study NCT05722015, 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)", were posted on 2025-07-28 on clinicaltrials.gov.