SYNC-T demonstrates high bone metastasis resolution in phase 1 cohort

The investigational platform combination therapy SYNC-T demonstrated high resolution of bone metastases in patients with metastatic castration-resistant prostate cancer and metastatic hormone-sensitive prostate cancer, according to data from a single-arm phase 1 trial presented at the 2025 Society of Urologic Oncology Annual Meeting in Phoenix, Arizona.¹

In their poster, the investigators, led by Gerald Andriole, MD, chief medical officer of Syncromune, Inc, explained that, “Conventional systemically administered immunotherapies for metastatic prostate cancer have limited efficacy and significant rates.”

Additionally, in a news release from Syncromune, co-author Charles J. Link, MD, said, “Bone metastases remain a clear unmet clinical challenge in metastatic prostate cancer with few durable responses, despite being present in more than 80% of advanced cases. Data demonstrating complete resolution of bone metastases at the rates we have observed is rare in this population, and it reinforces the potential of SYNC-T to elicit a well-tolerated, systemic immune response through an in situ approach.” Link is an adjunct professor at the Lankenau Institute for Medical Research and co-founder and executive chairman of Syncromune.²

According to the investigators, SYNC-T consists of a minimally-invasive, image-guided outpatient procedure that is initiated with partial oncolysis of a target tumor to release patient. Immediately after this, the patient receives an intratumorally delivered locoregional infusion of SV-102, “leading to immune system education, T cell activation, and a systemic anti-tumor response,” according to the investigators. The role of SYNC-T is synchronization of the location of patient-specific tumor antigens, SV-102, and immune cells in the tumor microenvironment along with locoregional lymph nodes. Targeting multiple mechanisms of cancer, SYNC-T incorporates a PD-1 inhibitor (abazistobart), a CTLA-4 inhibitor (futermestotug), a CD40 agonist (ciltistotug), and a TLR9 agonist (sitmutolimod).

At SUO 2025, the investigators presented data on an initial cohort of 15 patients who received SYNC-T, emphasizing radiographic resolution of bone metastases. Ten of these patients had failed hormone therapy and the remaining 5 refused hormone therapy. The primary objectives of the study were safety and toxicity; secondary objectives included efficacy, radiographic bone resolution, pharmacokinetics, and pharmacodynamics.

Patients received SYNC-T every 4 weeks for a maximum of 12 cycles (median, 6 cycles). During each treatment cycle, treatment was administered to a single tumor site, and the primary prostate tumor was targeted for each patient in the cohort. Patients were eligible for inclusion in the study if they had histologically confirmed prostate cancer, had failed previous treatment with 1 or more approved androgen receptor pathway inhibitors with or without prior chemotherapy or had refused hormone therapy, had measurable disease by RECIST 1.1 criteria, and had soft-tissue disease targetable by SYNC-T therapy. Patients were excluded if they had a known other primary malignancy other than prostate cancer with progression or that required active treatment within the previous 3 years, had an obstructed urinary system before or after stenting, or who had undergone a major surgical procedure or local prostate treatment within 28 days prior administration of the first SYNC-T treatment cycle.

A total of 8 (53%; 95% CI, 29-79) patients achieved a complete response, and 5 (33%) patients had a partial response. The overall response rate was 87%. All but 2 of the patients in the cohort had skeletal metastases at baseline (range, 1-54); 5 of these patients had more than 20 bone metastases. Following treatment with SYNC-T, all bone metastases had resolved in 7 of the 13 patients, which was confirmed via bone scan and/or prostate-specific membrane antigen-PET imaging.

Three deaths occurred in the cohort; at a median follow-up of 17 months, the survival rate was 80%. The median time to response was 2.9 months (range 1.8-4.8 months), and the median duration of response was 12.1 months (range, 1.1-24.1 months). Median rPFS was 14.2 months (range, 4.8-24.1 months), and median overall survival was not reached (range, 6.1-24.6 months).

The investigators said SYNC-T was well tolerated, with adverse events (AEs) occurring in 13 patients. Most (95%) AEs were grade 1 or 2, the most common of which were fever and hematuria. Two grade 2 immune-related AEs (hepatitis and hypothyroidism) and 2 grade 3 AEs (urinary retention and spinal compression) were observed. No grade 4 or 5 AEs were reported.

“For men with advanced prostate cancer, bone metastases are not only a major driver of pain and disability, but also represent one of the hardest challenges we face as clinicians. Seeing these lesions resolve in a meaningful proportion of patients treated with SYNC-T is very encouraging. Equally important is that SYNC-T was well tolerated in these heavily pre-treated physiologically fragile patients, who often have few remaining options that don’t carry significant toxicity. These findings suggest that in situ immune activation may offer a new path forward for patients who urgently need better and more tolerable therapies,” Andriole said in the news release.²

In the news release, Syncromune said patients are being enrolled for a multicenter phase 2 trial, called LEGION-100 (NCT06533644), at multiple US sites.²

REFERENCES

1. Andriole G, Link C, Kee S, et al. Effective resolution of bone metastases in patients with metastatic prostate cancer using SYNC-T therapy SV-102. Presented at: Society of Urologic Oncology Annual Meeting; December 2-5, 2025; Phoenix, Arizona. Abstract175. https://suo-abstracts.secure-platform.com/a/gallery/rounds/24/details/4748

2. Syncromune®, Inc. presents phase 1 data highlighting resolution of bone metastases in metastatic prostate cancer patients at Society of Urological Oncology 26th Annual Meeting. News release. December 4, 2025. Accessed December 5, 2025. https://syncromune.com/2025/12/04/syncromune-inc-presents-phase-1-data-highlighting-resolution-of-bone-metastases-in-metastatic-prostate-cancer-patients-at-society-of-urological-oncology-26th-annual-meeting/