Trial results for combining pembrolizumab and metformin in patients with metastatic head and neck squamous cell carcinoma were posted on ClinicalTrials.gov on 2026-05-08. The study found that patients receiving metformin before pembrolizumab demonstrated a median progression-free survival of 55.6% and overall survival of 77.8%, compared to 25.0% PFS and 55.5% OS when metformin was given after pembrolizumab.
Background
Head and Neck Squamous Cell Carcinoma is the condition studied in this trial. The trial investigated the combination of pembrolizumab and metformin extended release oral tablet.
Trial design
This Phase 2 study (NCT04414540) enrolled 21 participants with Head and Neck Squamous Cell Carcinoma. The trial's purpose was to determine anti-tumor activity by measuring overall response rate in recurrent and/or metastatic HNSCC patients receiving the combination of metformin and pembrolizumab. The study compared two intervention arms: Arm 1 involved participants receiving metformin before pembrolizumab, while Arm 2 involved participants receiving metformin after pembrolizumab. Primary outcomes were not specified in the posted results.
Key results
The trial measured several key outcomes:
- Overall Response Rate (ORR): In Arm 1: Metformin Before Pembrolizumab, 6 participants achieved an overall response. In Arm 2: Metformin After Pembrolizumab, 3 participants achieved an overall response.
- Number of Patients With Adverse Events: 10 participants in Arm 1: Metformin Before Pembrolizumab experienced adverse events, compared to 11 participants in Arm 2: Metformin After Pembrolizumab.
- Progression Free Survival (PFS): The median PFS was 55.6% (95% Confidence Interval) for Arm 1: Metformin Before Pembrolizumab, and 25.0% (95% Confidence Interval) for Arm 2: Metformin After Pembrolizumab.
- Overall Survival (OS): The median OS was 77.8% (95% Confidence Interval) for Arm 1: Metformin Before Pembrolizumab, and 55.5% (95% Confidence Interval) for Arm 2: Metformin After Pembrolizumab.
What this means
The results suggest a potential benefit when metformin is administered before pembrolizumab in patients with metastatic Head and Neck Squamous Cell Carcinoma. The higher median progression-free survival (55.6% vs 25.0%) and overall survival (77.8% vs 55.5%) in the "Metformin Before Pembrolizumab" arm indicate a potentially more favorable clinical outcome with this sequencing. The adverse event rates were comparable between the two arms (10 participants vs 11 participants), suggesting that the timing of metformin may impact efficacy without significantly altering the safety profile in this small study population.
Source
The information regarding these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for study NCT04414540, titled "Combining Pembrolizumab and Metformin in Metastatic Head and Neck Cancer Patients," were posted on 2026-05-08 on clinicaltrials.gov.