Introduction:

Introduction: Conventional forms of immunotherapy for metastatic prostate cancer have limited efficacy and relatively high rates 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 SV-102 combines device-induced partial cryolysis of a targeted tumor to create a personalized multi-antigen vaccine, followed immediately by intratumoral infusion of SV-102, leading to T-cell activation and an effective systemic immune response. SV-102 is comprised of 4 active ingredients: a PD-1 inhibitor, CTLA-4 inhibitor, CD40 agonist, and TLR9 agonist. Herein we report on the first 15 subjects treated with SYNC-T Therapy SV-102.

Methods:

Methods: 15 men with metastatic PCa (10 failed hormone therapy and 5 refused hormone therapy) were recruited into a single-arm Phase 1 study (NCT05544227). Some patients had also failed prior treatments with chemotherapy, immunotherapy, or radiation therapy. All were treated and evaluable and received the same dose of SV-102. All underwent SYNC-T Therapy q4 weeks for up to 12 cycles (median = 6). The primary prostate tumor was treated in all men in an outpatient procedure under conscious sedation or general anesthesia. 

Results:

Results: Median age was 61 (48-74). At baseline, 13 of 15 patients (87%) had skeletal metastases (ranging in number from 1-54); 5 of13 (38%) had >20 bone metastases.  After therapy, all bone metastases resolved in 7 of 13 (54%) patients.  Through May 1, 2025, 4 of those 7 (57%) patients have ongoing response.  

For the entire cohort, there were 8 (53%) CRs and 5 PRs for an ORR of 87%. Median time to response was 2.9 months; median duration of response was 12.1 months (range 1.1-24.1). Median rPFS was 14.2 months (range 4.8-24.1). Median OS has not been reached (range 6.1 to 24.6 months). 3 men died during follow-up, resulting in 80% survival at 17.2 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 and 2 Grade 3 TEAEs

Conclusion:

Conclusion: These data demonstrate initial proof of concept that prostate cancer bone metastases can be effectively treated by partial cryolysis of the primary tumor with intratumoral infusion of immunotherapeutic SV-102.  SYNC-T Therapy SV-102 has an acceptable safety profile and is being further evaluated in a Phase 2 multi-center US trial.  SYNC-T Therapy SV-102 potentially provides urologists with a new role in managing the treatment of metastatic prostate cancer. 

Funding: None