Trial results for the Phase 1 study (NCT02858869) investigating pembrolizumab in combination with stereotactic radiosurgery for melanoma or non-small cell lung cancer brain metastases were posted on ClinicalTrials.gov on 2026-03-09. The study reported no dose-limiting toxicities across any of the treatment arms, indicating a favorable safety profile in this initial phase.
Background
Pembrolizumab (Keytruda) is a monoclonal antibody that may interfere with the ability of tumor cells to grow and spread. This pilot trial investigated its use alongside stereotactic radiosurgery for patients with metastatic malignant neoplasm in the brain, specifically those with metastatic melanoma (including mucosal and ocular melanoma) or Stage IV non-small cell lung cancer that has spread to the brain.
Trial design
The Phase 1 study (NCT02858869) was a pilot trial that enrolled 25 participants. It investigated the combination of pembrolizumab with stereotactic radiosurgery in patients diagnosed with metastatic malignant neoplasm in the brain, including metastatic melanoma (mucosal and ocular melanoma) and Stage IV non-small cell lung cancer. The trial explored different fractionation schedules for stereotactic radiosurgery in combination with pembrolizumab, divided into three experimental arms.
Key results
The trial reported several key measurements across its experimental arms:
- Dose Limiting Toxicities:
- In Arm A (Pembrolizumab, 30 Gray (Gy) Over 5 Fractions), 0 Participants experienced dose-limiting toxicities.
- In Arm B (Pembrolizumab, 27 Gy Over 3 Fractions), 0 Participants experienced dose-limiting toxicities.
- In Arm C (Pembrolizumab, 18-21 Gy in One Fraction), 0 Participants experienced dose-limiting toxicities.
- Overall Survival (Median):
- Arm A (Pembrolizumab, 30 Gray (Gy) Over 5 Fractions): NA Months.
- Arm B (Pembrolizumab, 27 Gy Over 3 Fractions): 32.8 Months.
- Arm C (Pembrolizumab, 18-21 Gy in One Fraction): 12.2 Months.
- Rate of Symptomatic Radiation Necrosis:
- Arm A (Pembrolizumab, SRS 6 Gy): 0 Percentage of participants.
- Arm B (Pembrolizumab, SRS 9 Gy): 16.7 Percentage of participants.
- Arm C (Pembrolizumab, SRS 18-21 Gy): 14.3 Percentage of participants.
- Clinical Benefit (Intra-cranial):
- Arm A (Pembrolizumab, 30 Gray (Gy) Over 5 Fractions): 100 Percentage of participants.
- Arm B (Pembrolizumab, 27 Gy Over 3 Fractions): 60 Percentage of participants.
- Arm C (Pembrolizumab, 18-21 Gy in One Fraction): 20 Percentage of participants.
What this means
The results of this Phase 1 pilot trial suggest that pembrolizumab in combination with stereotactic radiosurgery is well-tolerated, with no dose-limiting toxicities observed across the different radiation fractionation schedules. While the overall survival and intracranial clinical benefit varied significantly between the arms (e.g., Arm B showing a median overall survival of 32.8 months and 60% intracranial clinical benefit, compared to Arm C with 12.2 months and 20%), these early findings provide valuable safety data to inform future studies. The absence of symptomatic radiation necrosis in Arm A is also noteworthy. These findings support further investigation into the optimal combination and dosing strategies for pembrolizumab and stereotactic radiosurgery in this patient population.
Source
The information regarding these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for study NCT02858869, titled 'Pembrolizumab and Stereotactic Radiosurgery for Melanoma or Non-Small Cell Lung Cancer Brain Metastases,' were posted on 2026-03-09 on clinicaltrials.gov.