There will be an abstract presented at the Upcoming (May 31- June 3) American Society of Clinical Oncologist Annual Meeting (ASCO) providing very preliminary data on a clinical trial combing Sipuleucel-T (Provenge) and enzalutamide (Xtandi) in men with metastatic castrate resistant prostate cancer (mCRPC).  This rational for conducting this trial is the lack of cross resistance of these two drugs as well as data suggesting that androgen ablation (enzalutamide is an androgen inhibitor) may potentiate the immunotherapeutic effects of vaccines, combining these agents may be a beneficial treatment approach for men with mCRPC.

This trial is a randomized, open-label phase II STRIDE trial (P12-2) designed to evaluate this combination.

Men with asymptomatic or minimally symptomatic mCRPC (the FDA label for Provenge) were randomized 1:1 to receive Provenge with enzalutamide (160 mg QD for 52 weeks).  There are two arms to the study; the concurrent arm (A) started Xtandi 2 weeks prior to Provenge and the sequential arm delayed Xtandi for 10 weeks after the start of Provenge

The primary endpoint is the peripheral of a T cell immune response.  This endpoint is not an approved biomarker but is often used to serve as an exploratory endpoint to prostate-specific antigen (PSA) recurrence.

As of January 14, 2013, 22 men have been enrolled. A total of 6 men have completed Sipuleucel-T treatment (3 in arm A and 3 in arm B); all received 3 infusions as per the FDA label. There were no significant differences in product potency between the arms; the median cumulative CD54 up-regulation (a measure of antigen-presenting cell [APC] activation) was 35.3 vs 26.6 and CD54+ cell counts were 1.9 vs 1.8 x109 in arms A and B, respectively. In all patients, APC activation was greater at infusion 2 vs 1 indicating an immunologic prime boost. Pre- and post-culture cellular composition did not differ between the arms.

Preliminary data from P12-2 suggest that sipuleucel-T can be manufactured during concurrent enzalutamide treatment with similar product potency as sipuleucel-T alone. Men receiving sipuleucel-T with concurrent enzalutamide appear to achieve an immunologic prime boost, consistent with other studies of sipuleucel-T. Additional data, including sipuleucel-T-induced peripheral immune responses, from >20 men will be presented at the meeting.

The data set as currently released only shows that concurrent use of these treatments doesn’t negatively impact the immune response created by Provenge.  The information to date (not concerning given the very early nature of the trial and the data) tells us nothing about the efficacy of the Xtandi in combination or in sequence with Provenge.  It tells us nothing of the potential survival advantage or disadvantage of combining these two treatments over their concurrent use.

Clinical trial information:   NCT01981122.

Abstract No:      e16071^

Author(s): David I. Quinn, Daniel Peter Petrylak, Christopher Michael Pieczonka, Andrew Sandler, Todd DeVries, Nadeem A. Sheikh, Charles G. Drake;

Joel T. Nowak, M.A., M.S.W.