Trial results for the combination of pembrolizumab and 177Lu-PSMA-617 in treating patients with metastatic castration-resistant prostate cancer were posted on ClinicalTrials.gov on 2025-02-25. The study reported an objective response rate (ORR) of 56 percentage of participants in the recommended Phase 2 dosing schedule part of the trial.
Background
Pembrolizumab (Keytruda) is an immunotherapy drug. 177Lu-PSMA-617 is a radioligand therapy that carries a radioactive component which attaches to the prostate specific membrane antigen (PSMA) receptor found on tumor cells, destroying them. The combination aims to leverage both mechanisms against castration-resistant prostate cancer that has spread to other parts of the body.
Trial design
This PHASE1 trial (NCT03805594) was completed and enrolled 43 participants. The study investigated the dose and schedule of 177Lu-PSMA-617 and pembrolizumab in patients diagnosed with Castration Levels of Testosterone, Castration-Resistant Prostate Carcinoma, Metastatic Prostate Carcinoma, Prostate Adenocarcinoma, and Stage IV Prostate Cancer. The trial did not list specific primary outcome measures in the results data.
Key results
Key measurements from the trial include:
- In Part A, the number of reported dose-limiting toxicities (DLT) was 0 dose-limiting toxicities for Dosing Schedule 1, 1 dose-limiting toxicity for Dosing Schedule 2, and 1 dose-limiting toxicity for Dosing Schedule 3.
- The objective response rate (ORR) in Part B, using the recommended Phase 2 dosing schedule, was 56 percentage of participants (95% Confidence Interval).
- The number of participants with treatment-related adverse events was 0 participants for Part A, Dosing Schedule 1; 1 participant for Part A, Dosing Schedule 2; 2 participants for Part A, Dosing Schedule 3; and 9 participants for Part B.
- The median duration of response was 8.1 months (Full Range).
- The prostate-specific antigen (PSA) response rate (PSA50) was 44 percentage of participants (95% Confidence Interval).
- The radiographic progression-free survival rate (rPFS) at 6 months was 51 percentage of participants (95% Confidence Interval).
- The median PSA progression-free survival was 6.9 months (95% Confidence Interval).
What this means
The results suggest that the combination of 177Lu-PSMA-617 and pembrolizumab demonstrates promising activity in patients with metastatic castration-resistant prostate cancer, evidenced by an objective response rate of 56% and a 6-month radiographic progression-free survival rate of 51%. The low number of dose-limiting toxicities observed in Part A indicates a potentially manageable safety profile for this combination, supporting further investigation in later-phase trials.
Source
The information regarding these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for study NCT03805594, titled "177Lu-PSMA-617 and Pembrolizumab in Treating Patients With Metastatic Castration-Resistant Prostate Cancer," were posted on 2025-02-25 on clinicaltrials.gov.