Trial results for the Phase 3 KEYNOTE-630 study (NCT03833167) investigating pembrolizumab as adjuvant therapy for locally advanced cutaneous squamous cell carcinoma (LA cSCC) were posted on ClinicalTrials.gov on 2025-07-22. The study found no statistically significant improvement in recurrence-free survival (RFS) with pembrolizumab compared to placebo, with median RFS of 53.3 months versus 53.7 months, respectively, and a p-value of 0.07243.
Background
The KEYNOTE-630 study investigated pembrolizumab (also known as Keytruda) as an adjuvant therapy. It was designed for participants with high-risk locally advanced cutaneous squamous cell carcinoma (LA cSCC) who had undergone surgery with curative intent in combination with radiotherapy.
Trial design
The KEYNOTE-630 study (NCT03833167) was a randomized, double-blind, Phase 3 trial that enrolled 450 participants. The study compared pembrolizumab with placebo as adjuvant therapy in participants with locally advanced cutaneous squamous cell carcinoma (LA cSCC) following surgery and radiation. The primary hypothesis was to assess if pembrolizumab was superior to placebo in increasing recurrence-free survival (RFS).
Key results
The trial evaluated several outcomes, including recurrence-free survival (RFS), overall survival (OS), and quality of life measures, as well as adverse events.
- For Recurrence-Free Survival (RFS) as assessed by the investigator:
- The median RFS for the pembrolizumab group was 53.3 Months.
- The median RFS for the placebo group was 53.7 Months.
An analysis using the Log Rank method showed a Hazard Ratio (HR) of 0.76 (95.0% CI: 0.53 to 1.1) with a p-value of 0.07243, indicating no statistically significant difference in RFS between the two groups.
- For Overall Survival (OS):
- The median OS for both the pembrolizumab group and the placebo group was reported as NA Months, meaning the median had not been reached at the time of data cutoff.
- For Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status and Quality of Life Combined Score:
- The least squares mean for the pembrolizumab group was -7.05 Score on scale.
- The least squares mean for the placebo group was -3.64 Score on scale.
The mean difference was -3.41 (95.0% CI: -8.91 to 2.09) with a p-value of 0.2227.
- For Change From Baseline in Physical Functioning Using the EORTC QLQ-C30 Items 1-5 Score:
- The least squares mean for the pembrolizumab group was -7.60 Scores on a scale.
- The least squares mean for the placebo group was -4.71 Scores on a scale.
The mean difference was -2.89 (95.0% CI: -7.19 to 1.42) with a p-value of 0.1874.
- Regarding Adverse Events (AEs):
- The percentage of participants who experienced an AE was 94.2% in the pembrolizumab group and 88.8% in the placebo group.
- The percentage of participants who discontinued study treatment due to an AE was 10.3% in the pembrolizumab group and 4.0% in the placebo group.
What this means
The results of the KEYNOTE-630 trial indicate that pembrolizumab as adjuvant therapy did not demonstrate a statistically significant improvement in recurrence-free survival compared to placebo in participants with locally advanced cutaneous squamous cell carcinoma who had undergone surgery and radiation. While the hazard ratio trended towards benefit for pembrolizumab, the p-value of 0.07243 and the confidence interval crossing 1.0 suggest that the primary endpoint of RFS superiority was not met. Additionally, the rate of adverse events and treatment discontinuations due to AEs was higher in the pembrolizumab arm, suggesting a less favorable safety profile without a clear efficacy benefit in this specific adjuvant setting.
Source
The information for these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for study NCT03833167, titled "Pembrolizumab (MK-3475) Versus Placebo Following Surgery and Radiation in Participants With Locally Advanced Cutaneous Squamous Cell Carcinoma (MK-3475-630/KEYNOTE-630)," were posted on 2025-07-22 on clinicaltrials.gov.