Randomized phase II trial of sipuleucel-T immunotherapy preceded by sensitizing radiation therapy and sipuleucel-t alone in patients with metastatic castrate resistant prostate cancer.

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222 Background: Sipuleucel-T (sip-T) is an autologous cellular vaccine indicated for patients (pts) with asymptomatic or minimally symptomatic metastatic castration resistant prostate cancer (mCRPC). Since radiation therapy (RT) can suppress the bone marrow function and immune response, previous studies evaluating sip-T excluded pts who received RT less than or equal to 28 days prior to sip-T therapy. Recent evidence suggests that RT may act synergistically with immunotherapy to enhance and broaden antitumor immune response. Methods: Pts who met standard criteria for sip-T were randomized to receive sip-T alone (Arm A) or sip-T initiated 1 week after completing sensitizing RT to single metastatic site (Arm B). RT was delivered at 300cGy/day to 3000 cGy total. The primary endpoint was the ability to safely combine sip-T preceded by RT and generate sip-T product with adequate immune activation parameters. Secondary endpoints included the measurement of immune responses to prostatic acid phosphatase (PAP) and PA20204 (recombinant fusion protein utilized in the generation of sip-T). Results: 51 pts were enrolled, 2 did not receive any sip-T because of vascular access problems and were excluded. 24 were treated on Arm A, 25 on Arm B. 47/49 pts received all 3 sip-T infusions. Median age was 66 yrs (range 45-90). Sip-T product parameters including: total nucleated cell (TNC) count, antigen presenting cell (APC) count and APC activation were similar in both groups. 2 pts on Arm A demonstrated PSA response. Median progression free survival (PFS) was 3.0 months on Arm A and 4.6 months on Arm B (p = 0.19). Both arms showed similar increases in humoral responses to PA2024 and PAP. IFN-ƴ ELISPOT T-cell activation responses to PA20204 were observed in both arms, but were more robust in the Arm A (p = 0.04). Both arms were well-tolerated, with fatigue as the most common grade 2 adverse event (1 pt in Arm A and 3 pts in Arm B). Conclusions: Sensitizing RT completed 1 week before generation of sip-T did not affect product parameters and the ability to deliver sip-T therapy. RT did not enhance the humoral and cellular responses associated with sip-T therapy. Clinical trial information: NCT01807065.