Trial results for the Phase 1 study (NCT02475213) investigating pembrolizumab in combination with enoblituzumab for patients with refractory melanoma, head and neck cancer, non-small cell lung cancer, and urothelial carcinoma were posted on ClinicalTrials.gov on 2025-08-11. The study primarily evaluated safety, reporting only 1 dose-limiting toxicity (DLT) across all cohorts.
Background
The study, titled 'Safety Study of Enoblituzumab (MGA271) in Combination With Pembrolizumab or MGA012 in Refractory Cancer,' aimed to evaluate the safety of enoblituzumab (MGA271) in combination with pembrolizumab (Keytruda) in patients with B7-H3-expressing melanoma, squamous cell carcinoma of the head and neck (SCCHN), non-small cell lung cancer (NSCLC), urothelial cancer, and other B7-H3 expressing cancers. It also sought to determine the highest safe dose of enoblituzumab when given with pembrolizumab and to assess pharmacokinetics and potential anti-tumor activity.
Trial design
The Phase 1 study (NCT02475213) was a completed trial that enrolled 146 participants. The study investigated enoblituzumab in combination with either pembrolizumab or retifanlimab in patients with melanoma, head and neck cancer, non-small cell lung cancer, and urothelial carcinoma. The primary objective was to evaluate the safety of the combination therapies and determine the maximum tolerated dose of enoblituzumab.
Key results
The trial results focused on safety and pharmacokinetic profiles. For the outcome of "Number of Participants With Dose-limiting Toxicities (DLT) After Administration of Enoblituzumab and Pembrolizumab or Retifanlimab":
- In Cohort 1, 1 participant experienced a DLT.
- In Cohort 2, 0 participants experienced a DLT.
- In Cohort 3, 0 participants experienced a DLT.
- In Cohort 4, 0 participants experienced a DLT.
Pharmacokinetic assessments for "Mean Maximum Concentration of Enoblituzumab" showed:
- Cohort 1: 223.5 mcg/mL (Standard Deviation: 62.80)
- Cohort 2: 860.0 mcg/mL (Standard Deviation: 434.1)
- Cohort 3 and Expansion Cohorts: 995.4 mcg/mL (Standard Deviation: 294.4)
- Cohort 4: 580.2 mcg/mL (Standard Deviation: 133.1)
For "Mean Trough Concentration of Enoblituzumab":
- Cohort 1: 146.2 mcg/mL (Standard Deviation: 48.1)
- Cohort 2: 551.0 mcg/mL (Standard Deviation: 323.7)
- Cohort 3 and Expansion Cohorts: 607.3 mcg/mL (Standard Deviation: 246.4)
- Cohort 4: 180.2 mcg/mL (Standard Deviation: 88.0)
What this means
The reported low number of dose-limiting toxicities (DLTs) across the study cohorts suggests a generally favorable safety profile for enoblituzumab in combination with either pembrolizumab or retifanlimab in patients with refractory cancers. These safety findings are crucial for informing further clinical development, particularly in determining appropriate dosing strategies for these combinations. The pharmacokinetic data provides insights into drug exposure, which is essential for optimizing future trial designs and potential therapeutic regimens.
Source
The information regarding these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for study NCT02475213, titled 'Safety Study of Enoblituzumab (MGA271) in Combination With Pembrolizumab or MGA012 in Refractory Cancer,' were posted on 2025-08-11 on clinicaltrials.gov.