VIR-5500 is a dual-masked T-cell engager designed to target prostate-specific membrane antigen (PSMA) for the treatment of metastatic castration-resistant prostate cancer (mCRPC). Early stage clinical trial data reveal promising safety and activity, particularly in heavily pre-treated patient populations.​

VIR-5500 utilizes the PRO-XTEN masking technology to selectively activate T-cell engagement within the tumor microenvironment, aiming to minimize systemic toxicity and adverse events in healthy tissues. The drug combines a bispecific approach, binding both PSMA on prostate cancer cells and CD3 on T-cells, with masking elements that are cleaved by proteases found in the tumor environment. This approach is intended to allow for stronger anti-tumor immune activity while simultaneously reducing the risk of off-tumor effects such as cytokine release syndrome (CRS) and neurotoxicity.​

The phase 1 clinical study  is ongoing and features dose escalation and expansion cohorts, both in monotherapy and in combination with androgen receptor pathway inhibitors (ARPIs). The trial has progressed to part 3, focusing on combination therapy with ARSI in taxane-naïve patients, with a goal to enroll 390 individuals across all study arms. Key endpoints include safety, pharmacokinetics, PSA response rate, and objective response rate (ORR). The study duration is planned at approximately 48 months.​

Interim results from the first two parts of the trial indicate that VIR-5500 is well-tolerated, with no dose-limiting toxicities identified. Adverse events were generally mild, with grade 1 and 2 CRS reported in a small number of patients. No grade 3 or higher CRS was seen. The favorable tolerability is attributed to the dual-masking mechanism, which helps prevent on-target, off-tumor toxicities.​

A PSA decline was observed in all patients who received at least one dose, with a confirmed reduction of at least 50% in 58% of cases. Further dose escalation may lead to deeper and more durable responses, based on trends seen in initial cohorts. The drug’s relatively long half-life (8–10 days) enables dosing every three weeks, which may improve convenience and adherence.​

VIR-5500 demonstrates activity even in patients with significant disease burden and prior extensive therapy, suggesting potential utility both as monotherapy and in combination regimens, including in earlier lines of metastatic prostate cancer. Its differentiated safety profile, especially regarding systemic immune toxicities, supports continued investigation and dose escalation. Future data will further clarify durability and depth of response, with ongoing trial expansion anticipated to address broader patient populations.​

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