Trial results for the Phase 2 study (NCT03526887) investigating pembrolizumab re-challenge in patients with advanced non-small cell lung cancer (NSCLC) were posted on ClinicalTrials.gov on 2025-03-24. The study, which included patients who had previously failed anti-PDL1 treatment, reported a median overall survival (OS) of 19.1 months for Cohort 2, significantly longer than 9.4 months for Cohort 1, with a p-value of 0.016 for the difference.

Background

Pembrolizumab (Keytruda) is an immunotherapy drug. This exploratory Phase 2 trial specifically investigated the re-challenge of pembrolizumab as a second or further line of treatment in patients with advanced non-small cell lung cancer (NSCLC) who had previously failed a prior treatment with an anti-PDL1 drug.

Trial design

The Phase 2 study (NCT03526887), titled "Re-challenge Pembrolizumab Study as a Second or Further Line in Patients With Advanced NSCLC," enrolled 73 participants with lung cancer, specifically advanced non-small cell lung cancer (NSCLC). The trial was designed as an exploratory study of intravenous pembrolizumab (MK-3475) administered as a second or further line of treatment in patients who had previously failed a prior anti-PDL1 drug. Participants received pembrolizumab 200 mg, Q3W, via IV infusion until disease progression.

Key results

The trial evaluated the efficacy of pembrolizumab re-challenge across two cohorts. Key measurements included overall survival (OS) and progression-free survival (PFS).

For Best Global Response, the participant counts for Cohort 1 were 0, 1, 24, and 25. For Cohort 2, the counts were 0, 3, 11, and 3.

A Log Rank analysis comparing the cohorts for overall survival indicated a median difference of 9.7 months (95.0% CI: 9.4 to 19.1) with a p-value of 0.016, suggesting a statistically significant difference in overall survival between the cohorts.

What this means

The results from this Phase 2 re-challenge study suggest that pembrolizumab may offer a survival benefit in certain advanced NSCLC patient populations who have previously failed anti-PDL1 therapy. The statistically significant difference in median overall survival, with Cohort 2 achieving nearly double the OS of Cohort 1, indicates a potential for improved outcomes. While the specific characteristics differentiating Cohort 1 and Cohort 2 are not detailed in the available data, these findings warrant further investigation into patient selection and optimal re-challenge strategies for pembrolizumab in this challenging clinical setting. The observed differences in PFS also support a differential treatment effect between the cohorts.

Source

The information for these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for study NCT03526887, titled "Re-challenge Pembrolizumab Study as a Second or Further Line in Patients With Advanced NSCLC," were posted on 2025-03-24 on clinicaltrials.gov.