Results from a phase 1 of study of 177Lu-PSMA-617 in combination with pembrolizumab show significant anti-tumor activity with low toxicity in patients with metastatic castration-resistant prostate cancer.
Pembrolizumab (Keytruda) plus a single priming dose of 177Lu-PSMA-617 (Pluvitco) demonstrated significant preliminary anti-tumor activity in patients with metastatic castration-resistant prostate cancer (CRPC), according to a press release on data from a phase 1 study (NCT03805594) from University of California San Francisco (UCSF) Health.1
Results from the trial demonstrated that 56% (95% CI, 35%-76%) of patients had an objective response to the treatment.2 Of those included in the overall cohort (n = 43), 5% experienced a complete response, and 47% had a confirmed partial response.
“This phase 1 trial represents the first clinical study to our knowledge to evaluate a single priming dose of targeted radioligand therapy coupled with immune checkpoint inhibition in patients with metastatic prostate cancer,” lead study author Rahul Aggarwal, MD, genitourinary medical oncologist and professor of medicine at UCSF, said in the press release.1 “We observed lasting responses in a subset of patients, in whom there was an increase in circulating T cells and decreased activity of immunosuppressive cells following the priming dose of 177Lu-PSMA-617.”
Supporting data for the positive responses came from an open-label, dose-expansion, non-randomized phase 1 clinical trial conducted by UCSF researchers.
The study included 43 patients with metastatic CRPC who received prior treatment with androgen signaling inhibitors.2 Patients received a priming dose of 177Lu-PSMA-617 and a sustained dose of pembrolizumab intravenously every 3 weeks.
The primary endpoint of part A of the study was determining the dose schedule for phase 2 of the trial. The primary endpoint of part B was objective response rate. Secondary endpoints included safety, dose-limiting toxicities, median duration of response, proportion of patients who had a decrease in prostate specific-antigen (PSA) of 50% or more from baseline, median PSA progression-free survival, median radiographic progression-free survival, and 6-month radiographic progression-free survival. Other secondary end points included median time to symptomatic skeletal related event, and median overall survival.
Investigators also reported a manageable safety profile associated with the study regimen. Overall, 5% of patients experienced grade 3 or higher treatment-related adverse effects, which included grade 3 arthritis and grade 3 pneumonitis in 1 patient each. The most common any-grade TRAEs included fatigue (60%), nausea (40%), and joint pain (33%). One death due to aspiration pneumonia was observed, which was not related to the study treatment.
Limitations to the study included the non-randomized nature of the trial. A phase 2 trial (NCT05766371) is expected to evaluate maintenance pembrolizumab in combination with multiple doses of 177Lu-PSMA-617 in order to assess anti-tumor response to treatment.
According to co-senior author Lawrence Fong, MD, leader of the Cancer Immunotherapy Program and an Efim Guzik Distinguished Professor in Cancer Biology at UCSF, findings from the phase 1 study show that a single dose of 177Lu-PSMA-617 combined with immunotherapy can have durable responses that are similar to those achieved with currently accepted treatment with 6 doses of 177Lu-PSMA-617.