SYNC-T SV-102 Employs Novel Mechanism to Target Immunologically ‘Cold’ Tumors in Advanced Metastatic Prostate Cancer

Following encouraging data in a phase 1 trial (NCT05544227) that demonstrated encouraging clinical activity with a manageable safety profile in patients with advanced metastatic prostate cancer, the novel in situ SYNC-T Therapy SV-102 is now being evaluated in the phase 2 LEGION-100 study (NCT06533644).SYNC-T is a combination drug/device immunotherapy platform and has the potential to address several unmet needs for patients by way of its unique multi-modal mechanism of action, according to Brian Myre, MD.^1,2

“SYNC-T SV-102 is a novel immunotherapy platform that takes a fundamentally different approach from therapies such as lutetium Lu 177 vipivotide tetraxetan [Pluvicto] or chemotherapy,” Myre explained in an interview with OncLive®. “ Rather than relying on systemic cytotoxicity or targeted radioligand therapy, it uses a local intervention to generate a systemic antitumor immune response. In the phase 1 [study], partial cryolysis to the prostate or lymph node was performed in patients with advanced disease, followed by an infusion of the fixed-dose, multi-target immunotherapy investigational drug SV-102. Essentially, we're taking a tumor that’s historically been immunologically cold with poor responses to checkpoint inhibitors and priming it by increasing the available antigens [via] cryolysis. Cryoablation releases tumor antigens, converting what has historically been an immunologically cold tumor into one that is more susceptible to immune recognition. SYNC-T SV-102 then combines PD-1 and CTLA-4 checkpoint blockade with CD40 and TLR9 agonists to stimulate both innate and adaptive immunity, with the goal of generating a durable systemic antitumor immune response.”

Myre is director of the Brian Moran Cancer Institute of Duly Health and Care and a medical oncologist at the Institute’s Center for Genitourinary (GU) Cancer Care in Lisle, Illinois.

What prior data have been reported with SYNC-T SV-102 in advanced metastatic prostate cancer?

During the 2025 ASCO Annual Meeting, investigators presented data from an open-label, single-arm phase 1 trial that evaluated the safety and efficacy of SYNC-T Therapy SV-102 in patients with histologically confirmed metastatic prostate cancer.¹ Eligible patients needed to have measurable disease per RECIST 1.1 criteria and at least one soft tissue lesion that can be targeted via the needle device delivery system. To be included in the study, patients also needed to experience failure of previous treatment with at least 1 FDA-approved second-generation androgen receptor pathway inhibitor, with or without previous chemotherapy, or refused hormonal therapy.

Following enrollment, patients received up to 12 cycles of the therapy via 4-week intervals to achieve the best response. The drug component of the therapy, SV-102, was administered at a fixed dose of 15 mL following cryolysis. Patients underwent baseline imaging via bone scan and/or PET/CT as well as MRI of the prostate. Response assessment occurred every 8 weeks, and following completion of the treatment, response durability assessment was measured every 12 weeks.

The primary endpoint was safety and toxicity, with secondary endpoints of overall response rate (ORR) per RECIST 1.1 criteria, radiographic progression-free survival (rPFS), and overall survival (OS). Pharmacokinetic and biomarker analyses were also evaluated as exploratory endpoints.

Findings from the phase 1 study revealed that patients who received SYNC-T Therapy SV-102 (n = 15) achieved a disease control rate of 100%. The ORR with this regimen was 87%, including a 53% (95% CI, 29%-79%) complete response (CR) rate. Further data from an independent radiological review showed that the ORR was 87% and the CR rate was 40%. Seven patients experienced a prostate-specific antigen (PSA) decline of over 50%; 2 others had a PSA level of less than 0.02 throughout treatment.

“None of the 15 patients experienced disease progression; 2 had stable disease,” Myre commented. “[Most] patients responded, and there were remarkably 8 CRs.”

The median time to response and median duration of response (DOR) were 2.9 months (range, 1.8–4.8) and 12.1 months (range, 1.1–22.4), respectively. The median rPFS was 14.2 months (range, 4.8–24.1) and the median OS was not reached (range, 6.1–24.6). The median follow-up for survival was 17.2 months, with 80% survival at that timepoint.

In terms of safety, the study authors noted that the therapy showed the ability to target multiple cancer mechanisms while avoiding systemic autoimmune adverse effects (AEs). The most common Grade 1/2 treatment-emergent AEs (TEAEs) included hematuria (4 of 15) and fever (3 of 15). Only two instances of Grade 2 immune-related AEs were reported (hypothyroidism and hepatitis) as well as two Grade 3 TEAEs (voiding problem and spinal cord compression). All adverse events were considered mild, with all Grade 1/2 AEs resolved. There were no Grade 4/5 AEs reported.

“When we think about checkpoint inhibition via immunotherapy, we see a lot of systemic TEAEs. The profile for safety for SYNC-T SV-102 is different [because] we’re treating locally, Myre underscored. [In addition to] the responses [that were observed], it’s promising in the sense of tolerability.”

What is the design of the LEGION-100 study?

LEGION-100 is a multicenter, dose-escalation and dose optimization phase 2a study of SYNC-T Therapy SV-102 in adult patients with metastatic castration-resistant prostate cancer.² Eligible patients must also have adequate serum testosterone levels, have experienced disease progression following treatment with at least 1 FDA-approved second-generation androgen receptor pathway inhibitors with or without a prior course of taxane therapy, have an ECOG performance status of 0 or 1, at least 1 measurable lesion per RECIST 1.1 criteria, and a life expectancy of at least 6 months.

“[LEGION-100] enrollment is open and ongoing in the United States. ”Myre said. “These are all now [patients with] castration-resistant [disease]. We're allowing [up to] 3 [prior] lines of therapy for castration-resistant disease. Either the prostate or a metastatic lesion can be targeted, including lung and exophytic bone lesions with a recent modification. This will allow more patients to get treated.”

LEGION-100 consists of dose-escalation (part 1) and dose-optimization (part 2) phases. During part 1, patients will undergo partial cryolysis plus an intratumoral infusion of SYNC-T Therapy SV-102 at 1 of 3 dose levels. Part 2 of the trial will evaluate two dose levels selected from part 1, with patients randomized to receive one or the other.

The primary endpoints are safety and ORR, as well as determining the recommended phase 2, maximum-tolerated, and optimal biologic dose levels. Secondary endpoints include DOR, rPFS, progression-free survival, OS, and pharmacokinetic measures. The study plans to enroll approximately 91 patients.

“We’ll have to wait for the phase 2 data with more patients to reproduce that [phase 1] response. How [SYNC-T Therapy SV-102] will fit in the landscape will depend, specifically in prostate cancer, but it's a novel way to treat cancer in general that allows these antigens to be presented and identified by the immune system to elicit a systemic anti-tumor response. I don't think the concept is necessarily specific, biologically to prostate cancer. We'll have to see those [phase 2] results and possibly how they expand to other solid tumors, including those that have been immunologically cold. [The study is] ongoing with more to be discovered, but [the findings have been] very encouraging so far,” Myre concluded.

References

1. Link CJ, Kee S, Prendergast GC, et al. Clinical responses to SYNC-T therapy: In situ personalized cancer vaccination with intratumoral immunotherapy in patients with metastatic castration-resistant prostate cancer (mCRPC). J Clin Oncol. 2025;43(suppl 16):2504. doi:10.1200/JCO.2025.43.16_suppl.2504
2. A study of SYNC-T therapy SV-102 in participants with metastatic castration-resistant prostate cancer. ClinicalTrials.gov. Updated June 23, 2026. Accessed June 25, 2026. https://clinicaltrials.gov/study/NCT06533644