Background: Immune responses to Sip-T in mCRPC patients (pts) correlate with survival (NEJM 2010;363:411). Adding Abi or Enz to Sip-T does not blunt Sip-T immune responses (CCR 2015;21:3862; JCO 2015;33 suppl:abs 5040). It is unknown if pts with primary resistance (1^ores) to Abi or Enz have impaired Sip-T immune responses. Methods: STAMP (NCT01487863) and STRIDE (NCT01981122) are similar randomized phase 2 studies. mCRPC pts received Abi (n=69) or Enz (n=52) concurrently (Con) with or sequentially (Seq) after Sip-T. In vitro immune activation was assessed by antigen presenting cell (APC) activation in each Sip-T product. In vivo immune responses were assessed by cellular (ELISPOT and proliferation assays) and humoral (ELISA) immune responses to target antigens PA2024 and PAP. Pts with a PSA decline from baseline (BL) of ³50% were defined as Abi/Enz sensitive (sens); those with <50% PSA decline had 1^o res. Immune responses in Abi/Enz sens and 1^ores pts were retrospectively analyzed, in each trial, in pooled Con vs Seq arms across trials, and for all pooled data. Results: The % of pts with Abi/Enz sens was similar across pooled arms (Con: 72%; Seq 68%). No differences were seen in in vitro or in vivo immune responses for Abi/Enz sens vs 1^ores pts at any time point (see Table). Conclusions: The magnitude of in vitro and in vivo immune responses after Sip-T appear to be independent of androgen sensitivity (i.e. PSA decline) to Abi or Enz, suggesting that Sip T therapy may have a role in pts with primary Abi or Enz resistance. Clinical trial information: NCT01981122 and NCT01487863

Median (^*range/^‡IQR); (%); ^§wk 6 for PA2024; ^#NS = not statistically significant at any time point, i.e. BL, wks 2, 4, 6, 10, 14, 20, 26, 40, 52, 56 for PA2024 and PAP (data not shown).