SYNC-T: Immunotherapy Platform Brings 4-Part Attack in Prostate Cancer, With More Trials Planned

Metastatic castration-resistant prostate cancer (mCRPC) has long resisted immunotherapy. Checkpoint inhibitors that transformed outcomes in melanoma and lung cancer have delivered response rates of just 3% to 4% as single agents in prostate cancer, and attempts to combine PD-1 and CTLA-4 blockade intravenously produced grade 3 or 4 toxicity in 40% to 50% of patients, ultimately derailing large phase 3 trials.^1,2

Against that backdrop, the SYNC-T platform developed by Syncromune, Inc is drawing attention by charting a different path.

“There’s still 80% or 85% who don’t respond to those drugs,” said Charles Link, MD, executive chairman and chief innovation officer for Syncromune, referring to the combination checkpoint inhibitor trials in an interview with The American Journal of Managed Care.® When patients received multiple types of drugs together, “the autoimmunity goes up because you just release the immune system too much.”

SYNC-T addresses that problem by working locally rather than systemically. With image guidance, a single needle is placed through the skin into a target tumor, Link explained. The tip partially freezes the tumor, disrupting cell membranes and releasing patient-specific antigens. This is immediately followed by an infusion directly into the tumor of SV-102, a 4-part regimen combining an anti–PD-1 monoclonal antibody, an anti–CTLA-4 monoclonal antibody, a CD40 agonist, and a TLR9 agonist.³

The goal, Link explained, is to synchronize tumor antigens, immune cells, and the drug within regional lymphatics, triggering T-cell activation and a systemic antitumor response—the so-called abscopal effect, a phenomenon in which a localized treatment in one tumor propels the shrinkage of untreated tumors located elsewhere in the body.⁴

“The business is really happening in the lymph nodes,” he said. “That’s where the immune cells are. That’s where the immune suppression is.”

The procedure takes roughly an hour under conscious sedation, which Link said is comparable to a colonoscopy, and is performed every 4 weeks for up to 12 cycles. Patients have reported no residual pain. Pharmacokinetic data showed that systemic exposure to SV-102 components was reduced by 97% to 99% compared with intravenous dosing, which Link said likely explains the dramatically cleaner safety profile.⁵

By mid-2024, interim phase 1 data presented at the American Association for Cancer Research Annual Meeting showed an objective response rate of 85% among 13 evaluable patients,⁶ prompting the FDA to grant fast-track designation for SV-102 that July, along with clearance of the investigational new drug application.⁷ All patients with stable disease or better were included in that signal, with 5 complete responses and 6 partial responses.^6,7

The final phase 1 data set (NCT05544227), presented as an oral abstract at the 2025 American Society of Clinical Oncology Annual Meeting, enrolled 15 evaluable patients with mCRPC, including 13 with bone metastases, who had failed or declined prior hormonal therapy. Among them, 8 achieved radiographic complete responses (53%; P = .0085 against a 20% null hypothesis) and 5 achieved partial responses, for an overall response rate of 87%. Median time to response was 3 months, with a median response duration of 12 months. Toxicity was minimal—95% of treatment-emergent adverse events were grade 1 or 2, with no grade 4 or 5 events observed.⁵

In April 2026, Syncromune presented updated safety and abscopal-effect data at the European Conference on Interventional Oncology in Basel, Switzerland, with median overall survival not yet reached at 17.2 months of follow-up.⁸

Link shared the story of a patient whose results highlight the therapy’s potential. A physician-surgeon with 50 skeletal metastases experienced a transient flare of bone-wide pain after treatment—an immune reaction Link had never seen before—followed by complete resolution of the bone lesions. “A couple weeks later, all the bone pain went away, and we did scans, and all the bone lesions went away,” Link recounted.

The technology is now advancing into the phase 2 LEGION-100-2a trial (NCT06533644), which Link said is enrolling across 40 to 50 US centers and sites in France, Japan, Hong Kong, New Zealand, and Mexico, targeting 60 to 80 patients total. A neoadjuvant trial in earlier-stage prostate cancer is also planned, enabled by SV-102’s favorable tolerability profile. Beyond prostate cancer, Link envisions future trials in breast, cervical, non–small cell lung, and small cell lung cancers, among others.

“It’s the best project I’ve worked on in my 30-year career,” Link said.

References

1. Antonarakis ES, Piulats JM, Gross-Goupil M, et al. Pembrolizumab for treatment-refractory metastatic castration-resistant prostate cancer: multicohort, open-label phase 2 KEYNOTE-199 study. J Clin Oncol. 2020;38(5):395-405. doi:10.1200/JCO.19.01638
2. Sharma P, Pachynski RK, Narayan V, et al. Nivolumab plus ipilimumab for metastatic castration-resistant prostate cancer: preliminary analysis of patients in the CheckMate 650 trial. Cancer Cell. 2020;38(4):489-499.e3. doi:10.1016/j.ccell.2020.08.007
3. A potentially game-changing approach to treating metastatic cancer. Syncromune. Accessed June 24, 2026. https://syncromune.com/science/#platform
4. Smesseim I, Perez PN, Chachoua A, Cooper BT, Sterman DH. Defining the abscopal effect in non-small cell lung cancer in the era of immunotherapy and lung ablation treatment: a narrative review. Front Med (Lausanne). 2026;13:1804711. doi:10.3389/fmed.2026.1804711
5. 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
6. Syncromune Inc presents positive results from SYNC-T SV-102 phase 1 trial at AACR Annual Meeting 2024. News release. Syncromune Inc. April 8, 2024. Accessed June 24, 2026. https://syncromune.com/2024/04/08/syncromune-inc-presents-positive-results-from-sync-t-sv-102-phase-1-trial-at-aacr-annual-meeting-2024/
7. Syncromune granted FDA fast-track designation for SYNC-T SV-102 for the treatment of metastatic castrate-resistant prostate cancer (mCRPC). News release. Syncromune. July 1, 2024. Accessed June 25, 2026. https://bit.ly/4uS5vlL
8. Syncromune, Inc. presents innovative SYNC-T combination immunotherapy approach at major European interventional oncology conference. News release. Syncromune Inc. April 29, 2026. Accessed June 24, 2026. https://bit.ly/4eHOapF