ClinicalTrials.gov recorded primary completion on 12 July 2024 for a Phase 3 study of subcutaneous pembrolizumab formulated with berahyaluronidase alfa versus intravenous pembrolizumab in adults with metastatic non-small cell lung cancer. The trial enrolled 377 participants and evaluated pharmacokinetics and safety when pembrolizumab was administered with platinum doublet chemotherapy. Listed pharmacokinetic measures were higher for the subcutaneous formulation for several exposure endpoints, including steady-state AUC and trough concentration.

Background

The study evaluated pembrolizumab, also identified in the registry as Keytruda, in a subcutaneous formulation coformulated with berahyaluronidase alfa. It compared that formulation with intravenous pembrolizumab during first-line treatment of adults with metastatic non-small cell lung cancer. The registered chemotherapy interventions included pemetrexed, cisplatin, carboplatin, and paclitaxel.

Trial design

This was a Phase 3 trial, NCT05722015, with 377 participants and a condition of metastatic non-small cell lung cancer. The study status was active, not recruiting. Its primary hypotheses concerned whether subcutaneous pembrolizumab was noninferior to intravenous pembrolizumab for pharmacokinetic parameters. The listed treatment groups were subcutaneous pembrolizumab formulated with berahyaluronidase alfa plus platinum doublet chemotherapy, and intravenous pembrolizumab plus platinum doublet chemotherapy.

Key results

After the first dose, the cycle 1 geometric mean AUC from zero to six weeks was 1,633.24 μg·day/mL with the subcutaneous formulation versus 1,437.58 μg·day/mL with intravenous pembrolizumab. The geometric coefficient of variation was 40.41% and 26.23%, respectively.

At steady state in cycle 3, the geometric mean AUC was 2,798 μg·day/mL for subcutaneous treatment versus 2,122 μg·day/mL for intravenous treatment. Steady-state trough concentration was 39.23 μg/mL versus 23.49 μg/mL, while maximum concentration was 98.96 μg/mL versus 148 μg/mL, respectively.

Two registry analyses used Welch’s t test. They reported a geometric mean ratio of 1.14 with a 96.0% confidence interval of 1.06–1.22 and a p-value of 1e-05; a second analysis reported a ratio of 1.67 with a 94.0% confidence interval of 1.52–1.84 and a p-value of 1e-05. The supplied record did not identify which specific measurements these analyses represented.

What this means

The listed results showed higher subcutaneous geometric mean exposure for several AUC and trough measures, while cycle 1 and steady-state maximum concentrations favored different treatment groups. The record included no adverse-event summary and did not establish a new approval or indication.

Source

Source: ClinicalTrials.gov, trial record for NCT05722015, event date 12 July 2024. The registry record is available at clinicaltrials.gov/study/NCT05722015.