Trial results for the Phase 1/2 study (NCT02638090) investigating pembrolizumab in combination with vorinostat for Stage IV non-small cell lung cancer (NSCLC) were posted on ClinicalTrials.gov on 2025-05-04. The combination arm demonstrated an objective response rate (ORR) of 41%, compared to 28% for pembrolizumab monotherapy.
Background
The study investigated pembrolizumab (Keytruda), an immunotherapy approved by the U.S. Food and Drug Administration (FDA) for melanoma and lung cancer, and vorinostat, which is approved to treat some forms of blood cancer. This trial explored their combination for advanced non-small cell lung cancer.
Trial design
The PHASE1/PHASE2 study (NCT02638090) enrolled 120 participants with Stage IV non-small cell lung cancer (NSCLC). The trial aimed to assess the safety and efficacy of combining pembrolizumab and vorinostat. Participants were assigned to either Arm A, receiving pembrolizumab alone, or Arm B, receiving pembrolizumab plus vorinostat. The study also included a Phase 1 dose escalation to determine the maximum tolerated dose of vorinostat.
Key results
Key results from the trial included findings from both Phase 1 and Phase 2 portions.
From the Phase 1 dose escalation, the maximum tolerated dose (MTD) of vorinostat was determined to be 400 Milligrams of Vorinostat.
In the Phase 2 portion, evaluating Progression Free Survival (PFS) and Objective Response Rate (ORR) per treatment arm:
- For Progression Free Survival (PFS), the median PFS for Arm A: Pembrolizumab was 4.5 Months. For Arm B: Pembrolizumab Plus Vorinostat, the median PFS was 4.3 Months.
- For Objective Response Rate (ORR), Arm A: Pembrolizumab showed an ORR of 28 Percentage of Participants with OR. Arm B: Pembrolizumab Plus Vorinostat demonstrated an ORR of 41 Percentage of Participants with OR.
What this means
The trial results indicate that while the addition of vorinostat to pembrolizumab did not extend median progression-free survival in patients with Stage IV non-small cell lung cancer, it did lead to an increase in the objective response rate. The 41% ORR observed with the combination compared to 28% with pembrolizumab alone suggests a potential benefit in tumor response for this patient population. Further investigation into the clinical significance of this improved ORR in the context of PFS is warranted.
Source
The information for these trial results was sourced from ClinicalTrials.gov, a public database of clinical studies. The results for study NCT02638090, titled 'Pembro and Vorinostat for Patients With Stage IV Non-small Cell Lung Cancer (NSCLC),' were posted on 2025-05-04 on clinicaltrials.gov.