Trial results for the Phase 1 study (NCT03307759) investigating the sequencing of pembrolizumab with stereotactic ablative body radiotherapy (SABR) in metastatic non-small cell lung carcinoma (mNSCLC) were posted on ClinicalTrials.gov on 2025-09-15. The study found that 80% of participants achieved overall survival when SABR was given before pembrolizumab, compared to 50% when pembrolizumab was given first.
Background
Pembrolizumab (Keytruda) is an intervention used in the treatment of non-small cell lung cancer (NSCLC). This study explored its combination with stereotactic ablative body radiotherapy (SABR).
Trial design
The study (NCT03307759) was a Phase 1, investigator-driven trial that enrolled 13 participants with metastatic non-small cell lung carcinoma. It investigated the safety, efficacy, and biological effects of two schedules of pembrolizumab in combination with stereotactic ablative body radiotherapy (SABR). Participants received pembrolizumab either before or after SABR.
Key results
The trial evaluated safety and efficacy outcomes across two treatment sequencing arms:
- SABR Plus Pembrolizumab (SABR given before pembrolizumab)
- Pembrolizumab Plus SABR (pembrolizumab given before SABR)
For adverse events measured using CTCAE Version 4.03, there were 0 participants with Grade 3 treatment-related adverse events (TRAEs) in the SABR Plus Pembrolizumab group, compared to 1 participant in the Pembrolizumab Plus SABR group.
Overall response rates, assessed by various criteria, showed similar numbers of responders between the two groups:
- Using RECIST 1.1, 4 participants in each group achieved an overall response (CR + PR).
- Using irRECIST, 4 participants in each group achieved an overall response (irCR + irPR).
- Using PERCIST 1.0, 3 participants in each group achieved an overall response (CMR + PMC).
- Using Peter Mac Metabolic Response Criteria, 3 participants in the SABR Plus Pembrolizumab group and 4 participants in the Pembrolizumab Plus SABR group achieved an overall response (CMRv + PMRv).
Regarding overall survival, the trial reported a percentage of participants with overall survival of 80% for the SABR Plus Pembrolizumab group, compared to 50% for the Pembrolizumab Plus SABR group.
What this means
These Phase 1 results suggest potential differences in outcomes based on the sequencing of pembrolizumab and SABR in metastatic NSCLC. While overall response rates were largely similar across various assessment methods, the higher percentage of participants with overall survival observed when SABR was administered before pembrolizumab warrants further investigation. The safety profile also showed a numerically lower incidence of Grade 3 TRAEs in the SABR-first sequence, though this was based on a very small patient cohort.
Source
The results for study NCT03307759, titled "Sequencing of Stereotactic Ablative Body Radiotherapy in Combination With PD-1 Blockade Using Pembrolizumab in Metastatic Non-Small Cell Lung Carcinoma," were posted on 2025-09-15 on ClinicalTrials.gov.