UPDATE: VIR-5500 Results From Phase 1 Trial Look Very Promising

Recent clinical data from a Phase 1 dose-escalation trial highlight VIR-5500 as a highly promising therapeutic candidate for patients with heavily pre-treated metastatic castration-resistant prostate cancer (mCRPC).
VIR-5500 is a dual-masked, bispecific T-cell engager designed to selectively target the prostate-specific membrane antigen (PSMA) while minimizing systemic toxicity. The therapy employs a specialized PRO-XTEN masking technology that keeps the drug inactive in healthy tissues, only allowing it to bind to T-cells and tumor cells once it is cleaved by proteases specific to the tumor microenvironment.

The updated results from the Phase 1 trial involving 58 patients demonstrated profound, dose-dependent anti-tumor activity. In the highest dosing cohorts (receiving 3,000 µg/kg or more every three weeks), 82% of patients achieved at least a 50% reduction in prostate-specific antigen (PSA50) levels, and 53% achieved a 90% reduction (PSA90). Furthermore, among patients evaluable by RECIST criteria in these high-dose groups, VIR-5500 yielded a 45% objective response rate (5 out of 11 patients). These robust radiographic and biochemical responses signify strong efficacy in a late-stage patient population that has exhausted most existing therapeutic options.

Equally important to its efficacy is the drug’s highly favorable safety and tolerability profile, which validates the underlying tumor-selective masking strategy. Across all 58 patients receiving monotherapy, VIR-5500 was generally well tolerated with zero dose-limiting toxicities observed to date. Grade 3 or higher treatment-related adverse events occurred in only 12% of participants (7 out of 58 patients) and were considered manageable. Notably, instances of cytokine release syndrome (CRS), a common and often severe complication with traditional T-cell engagers, were minimal, with approximately 50% of patients experiencing only mild, Grade 1 symptoms such as fever. Driven by this distinct therapeutic index, the clinical program is now advancing to dose-expansion cohorts and combination regimens, with plans for pivotal registrational trials in 2027.

Source.

Clinical trial.