Restoring tumor-specific immunity is a treatment strategy that has worked well, but only against some cancers. Research led by OHSU oncologist Julie Graff, M.D., revived hope that the approach may help men with life-threatening prostate cancer.

And now it’s advanced to a phase 3, multi-center clinical trial. Graff, an associate professor in the OHSU School of Medicine, presented the phase 2 results on Feb. 13 at the ASCO Genitourinary Cancers Symposium 2020 in San Francisco.

Men with metastatic prostate cancer resistant to androgen deprivation therapy and the androgen receptor antagonist enzalutamide were treated with pembrolizumab, a monoclonal antibody that binds to the PD-1 receptor. Subjects received pembrolizumab and continued to take enzalutamide.

Graff in 2016 published the first evidence of meaningful clinical activity for PD-1 blockade in men with aggressive, advanced-stage prostate cancer. It was a preliminary study with 10 subjects, but an encouraging result because prior studies of men with metastatic prostate cancer showed no evidence of anti-tumor activity with immune therapies that work by blocking PD-1 signals.

The phase 2 study, sponsored by Merck Sharp & Dohme Corp., included 126 subjects. After a median follow-up of nearly 14 months, the overall response rate was 12% in the cohort of 81 subjects with RESIST measurable disease. The disease control rate for all subjects was 51%.

The combination had manageable safety, Graff and colleagues concluded. About a quarter of men experienced treatment-related adverse events of grade 3 to 5. Two died of immune-related adverse events.

“These data confirm that there can be response to pembrolizumab in this setting and give us a better idea of the response rate,” Graff said. “This is just one rung on the ladder of getting a new treatment out there. The phase 3 clinical trial will be more definitive.”

That study is open and enrolling at OHSU and a multitude of other trial sites. Graff is the global principal investigator.