Clinical responses to SYNC-T therapy: In situ personalized cancer vaccination with intratumoral immunotherapy in patients with metastatic castration-resistant prostate cancer (mCRPC).

Abstract

2504 Background: Metastatic castration-resistant prostate cancer (mCRPC) has a poor response to immunotherapy limited by both a low ORR and high frequency of severe immune-related adverse events. SYNC-T is a novel in situ therapy that synchronizes the presence of tumor antigens, an immune therapy drug, and immune cells in the tumor and locoregional lymph nodes. SYNC-T Therapy combines device-induced partial cryolysis of a targeted tumor to create a personalized multi-antigen vaccine, followed immediately by intratumoral infusion of the multitarget novel drug candidate SV-102, leading to T-cell activation and an effective systemic immune response. Methods: 15 subjects, 13 with bone metastases, and documented failure to prior hormonal therapy (n = 10) or refused therapy (n = 5) were recruited to a single-arm study (NCT05544227). Image-guided partial cryolysis of a tumor was followed by intratumoral infusion of SV-102, comprised of fixed low dose of anti-PD-1 mAb, anti-CTLA4 mAb, CD40 agonist mAb, and TLR9 agonist CpG-ODN. All subjects received the same dose of SV-102. Subjects received SYNC-T Therapy q4 weeks for up to 12 cycles (median = 6). One site of primary prostate or soft tissue metastasis was targeted at each cycle. Primary objective was to evaluate safety and tolerability with a secondary objective to assess tumor response by PCWG3 and RECIST 1.1. Results: 15 subjects were treated and evaluable. Median age was 61 (48-74). Prior treatments included one or more of 1 st , 2 nd generation hormonal blockade, chemotherapy, immunotherapy, or radiation therapy. Within 15 evaluable subjects there were 8 radiographic CRs (53%, the two-sided 95% CI is 29.4% to 78.7%, rejecting 20% CR null hypothesis; p = 0.0085) with complete resolution of primary, bone, and soft tissue metastases and 5 PRs with an ORR of 87%. Median time to response was 3 months with a median duration of 12 months to date (range 1.2 -14.6). Among the 15 subjects, 3 have died resulting in 80% survival with 14 months median follow-up. SYNC-T Therapy was well-tolerated with 41 TEAEs in 13 subjects. The majority (95%) of TEAEs were Grade 1 or 2, most commonly fever and hematuria. There were 2 Grade 2 irAEs of hepatitis and hypothyroidism and 2 Grade 3 TEAEs of urinary retention and spinal cord compression. PSA analysis during and post SYNC-T Therapy will be presented. PK analysis revealed minimal systemic exposure to SV-102 components. PD analysis showed induction of inflammatory cytokines and the emergence of multiple, novel T-cell clones. Conclusions: SYNC-T Therapy was well-tolerated achieving an 87% ORR in subjects with mCRPC or who refused ADT. These encouraging clinical results have led to further study of SYNC-T SV-102 in a US, multicenter, Phase 2a trial for subjects with mCRPC. Clinical trial information: NCT05544227 .