Trial results for a study investigating subcutaneous Nivolumab monotherapy, with or without recombinant human hyaluronidase PH20 (rHuPH20), were posted on ClinicalTrials.gov on 2025-02-20. The study characterized the pharmacokinetic profile of various subcutaneous formulations and doses, reporting maximum observed serum concentrations (Cmax) and time to Cmax (Tmax) across different treatment arms.
Background
Nivolumab is an immunotherapy drug approved for several advanced or metastatic tumors. Administered intravenously, it targets the PD-1 pathway. This study aimed to explore subcutaneous administration, which could offer a more convenient treatment option for patients. The trial included participants with advanced or metastatic non-small cell lung cancer (NSCLC), renal cell carcinoma (RCC), unresectable or metastatic melanoma, hepatocellular carcinoma (HCC), and microsatellite instability-high or mismatch repair deficient colorectal cancer (MSI-H/dMMR CRC), among other solid tumors.
Trial design
This completed Phase 1/Phase 2 study (NCT03656718) enrolled 139 participants. The trial's purpose was to investigate the effects of Nivolumab when given under the skin, with or without rHuPH20. Participants had various advanced or metastatic tumors. The study explored several subcutaneous regimens, including Nivolumab alone and Nivolumab combined or co-formulated with rHuPH20 at different doses and frequencies.
Key results
The study reported key pharmacokinetic measurements, including maximum observed serum Nivolumab concentration (Cmax) and time taken to reach Cmax (Tmax).
- For Cmax, the geometric mean values observed were:
- Part A - Group 1: Nivolumab + rHuPH20 SC 720mg: 54.8 ug/mL (Geometric Coefficient of Variation: 51.0)
- Part B - Group 2: Nivolumab SC 720mg: 56.6 ug/mL (Geometric Coefficient of Variation: 34.0)
- Part B - Group 3: Nivolumab + rHuPH20 SC 960mg: 81.4 ug/mL (Geometric Coefficient of Variation: 41.0)
- Part B - Group 4: Nivolumab SC 960mg: 63.9 ug/mL (Geometric Coefficient of Variation: 30.0)
- Part D: Nivolumab SC + rHuPH20 SC 1200mg Q4W: 106.0 ug/mL (Geometric Coefficient of Variation: 46.0)
- Part E: Nivolumab SC Co-Formulated With rHuPH20 600mg Q2W: 57.8 ug/mL (Geometric Coefficient of Variation: 31.0)
- For Tmax, the median values observed were:
- Part A - Group 1: Nivolumab + rHuPH20 SC 720mg: 167 hours
- Part B - Group 2: Nivolumab SC 720mg: 167 hours
- Part B - Group 3: Nivolumab + rHuPH20 SC 960mg: 141 hours
- Part B - Group 4: Nivolumab SC 960mg: 168 hours
- Part D: Nivolumab SC + rHuPH20 SC 1200mg Q4W: 130 hours
- Part E: Nivolumab SC Co-Formulated With rHuPH20 600mg Q2W: 130 hours
What this means
These pharmacokinetic results provide important data on the absorption and concentration profiles of subcutaneous Nivolumab. The varying Cmax values across different doses and formulations, including those with rHuPH20, indicate that subcutaneous delivery can achieve systemic exposure. The Tmax data suggests the time required to reach peak concentrations. This information is critical for optimizing subcutaneous formulations of Nivolumab, potentially offering patients a more convenient administration method compared to intravenous infusions, while maintaining therapeutic drug levels.
Source
The information regarding these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for study NCT03656718, titled "A Study of Subcutaneous Nivolumab Monotherapy With or Without Recombinant Human Hyaluronidase PH20 (rHuPH20)," were posted on 2025-02-20 on clinicaltrials.gov.