In the era of immunotherapy, significant efforts have been made to study anti-PD-1 therapies in the mCRPC space. The very first study showed no response for patients (n=17) with mCRPC5. Subsequent studies have shown that there may be some durable responders, but efficacy appears limited6,7. Thus, combination therapies are being investigated to stimulate both innate and adaptive tumor-specific immunity.
ADXS-PSA is a bioengineered attenuated Listeria monocytogenes-based immunotherapy that targets PSA. The goal of this therapy is to increase the antigen-specific effector T cells which kill tumor cells while at the same time decreasing the ratio of immune regulating cells to immune effector cells, counteracting the immunosuppressive tumor microenvironment.
In the dose finding portion of this study, patients (n=14) received increasing doses 1x109; 5 x109 and 1x1010 colony forming units IV every 3 weeks. During the second part of the study, patients (n=37), all received 1x109 CFU + 200 mg pembrolizumab every 3 weeks with a 4th pembrolizumab dose 3 weeks later, for up to 2 years or until progression or toxicity.
In the combination arm, 16 (43%) patients had a PSA decline from baseline. Of the 16 patients, 8 (22%) had a PSA reduction ≥50% of baseline, which was confirmed in 3 (38%) patients. At the time of this abstract, tumor measurements were available for 23 patients in the combination arm – 10 of these patients had stable disease per RECIST criteria. Of note, at this time, there are no radiographic objective responses to therapy. With regards to adverse events, most have been grade 1-2, with flu like symptoms and hypertension. At this time, median survival has not yet been reached for the combination arm – we will need to see more mature data before predicting whether or not there will be an overall survival benefit.
Combination therapy with an immunotherapy backbone is an area of heavy interest at the moment, with several checkpoint inhibitor studies, many in combination with vaccine therapies. Monotherapy, such as sipuleucel T, has modest benefits, but because of the low mutational burden in prostate cancer, there likely needs to be another agent to synergize with for maximum clinical benefit.
Presented By: Mark N. Stein, MD, MD. Columbia University Medical Center
Poster discussion by: Winald R. Gerritsen, Radboud University Medical Center
Written by: Jason Zhu, MD Fellow, Division of Hematology and Oncology Duke University Medical Center, Twitter: @TheRealdJasonZhu at the 2018 ASCO Annual Meeting - June 1-5, 2018 – Chicago, IL USA
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