VIR-5500 Receives FDA Fast Track Designation for Late-Line Metastatic CRPC

The FDA has granted fast track designation to VIR-5500, a prostate-specific membrane antigen (PSMA)-targeted PRO-XTEN® dual-masked T-cell engager (TCE), for the treatment of late-line metastatic castration-resistant prostate cancer (CRPC), according to a news release from the developer, Vir Biotechnology.¹

The designation, which is intended to facilitate and expedite development and review for drugs that treat serious conditions and fill an unmet need, follows preliminary phase 1 data presented earlier this year demonstrating meaningful antitumor activity in a heavily pretreated patient population. Phase 3 trials are anticipated to begin in 2027.

What phase 1 data supported the fast track designation for VIR-5500?

Preliminary dose-escalation results from the first-in-human phase 1 study VIR-5500-V101 (NCT05997615) were presented at the 2026 American Society of Clinical Oncology Genitourinary Cancers Symposium by Johann S. de Bono, MD, Regius Professor of Cancer Research and a professor in Experimental Cancer Medicine at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust in London, UK.² The study enrolled 58 patients across weekly (n = 26) and every-3-weeks (n = 32) dose-escalation cohorts, with all dose-escalation cohorts clearing the dose-limiting toxicity (DLT) threshold.

The population was heavily pretreated, with a median 4 prior lines of therapy (range, 2–7). A total of 94.8% received prior taxane, 100% received prior androgen receptor pathway inhibitor (ARPI), and 12.1% received prior PSMA-radioligand therapy. The baseline median PSA was 79 ng/mL (range, 4–3708), with 92.9% bone metastases and 44.6% visceral metastases including 17.9% with liver involvement.

What were the efficacy results at higher VIR-5500 doses?

Among 17 PSA-evaluable patients treated at doses of 3000 μg/kg or higher every 3 weeks, VIR-5500 demonstrated a dose-dependent pattern of deep and durable PSA reductions. 50% or greater PSA decline from baseline (PSA50) was achieved in 82% of patients (n = 14/17), 90% or greater PSA decline (PSA90) in 53% (n = 9/17), and 99% or greater PSA decline (PSA99) in 29% (n = 5/17). PSA declines were observed as early as cycle 1, day 8. Among the 11 patients with RECIST-evaluable disease at doses of 3000 μg/kg or higher every 3 weeks, the objective response rate (ORR) was 45% (n = 5/11), with all 4 confirmed responders achieving confirmation up to week 27; the disease control rate (DCR) was 64% (n = 7/11).

What is the safety profile of VIR-5500?

VIR-5500 demonstrated a favorable safety profile across the dose-escalation program. Grade 3 or higher treatment-related adverse events (TRAEs) occurred in 12.1% (n = 7/58) of patients, and 2 patients (3.4%) discontinued treatment due to a treatment-emergent AE. Cytokine release syndrome (CRS) was predominantly grade 1, with no grade 3 CRS and no immune effector cell–associated neurotoxicity syndrome (ICANS) reported.

No prophylactic corticosteroids or anti-interleukin-6 therapy were required at doses up to 3500 μg/kg Q3W, and predominantly low levels of IL-6 were detected post-treatment. No DLTs were observed across the full program. The most frequently reported grade 1/2 events at doses of 3000 μg/kg or higher every 3 weeks included CRS (grade 1: 50%; grade 2: 9%), back pain (14%), fatigue (14%), anemia (grade 2: 14%), and infusion-related reactions (18%).

“Receiving fast track designation reflects the potential of VIR-5500 to address an area of serious unmet need in late-line [metastatic] CRPC and the strong momentum we have achieved with Astellas as we prepare to enter pivotal phase 3 development in 2027,” stated Marianne De Backer, president and chief executive officer of Vir Biotechnology, in the press release.¹ “We look forward to working with the FDA to rapidly advance the development of VIR-5500 for people living with [metastatic] CRPC.”

What is VIR-5500 and how does the PRO-XTEN masking technology work?

VIR-5500 is a bispecific TCE designed to engage PSMA on prostate cancer cells and CD3 on T cells, directing cytotoxic T-cell activity toward tumor cells. Distinguishing VIR-5500 from conventional TCEs is the proprietary PRO-XTEN® dual-masking platform, originally developed by Amunix Pharmaceuticals.

In conventional TCEs, simultaneous engagement of CD3 in peripheral blood can lead to severe systemic toxicity, particularly CRS, which has historically limited the use of TCEs in solid tumors. The PRO-XTEN® masks keep VIR-5500 inactive in circulation until the molecule reaches the tumor microenvironment, where tumor-specific proteases cleave the masks and activate the TCE. The masking technology is additionally designed to extend the molecule’s half-life, allowing it to accumulate at the tumor site and potentially enabling less-frequent dosing.

What is the unmet need in late-line mCRPC?

Prostate cancer is the second leading cause of cancer-related mortality in men, trailing only lung cancer. The disease commonly progresses through stages of androgen sensitivity toward metastatic hormone-sensitive prostate cancer (HSPC) and ultimately metastatic CRPC, a stage associated with poor clinical outcomes and a 5-year survival rate of approximately 30%. Existing approved therapies, including novel hormonal agents, taxane-based chemotherapy, PARP inhibitors, and radioligand therapy, offer meaningful but generally non-durable benefit in this setting. The heavily pretreated patient population enrolled in VIR-5500-V101, with a median of 4 prior lines and 92.9% bone metastases, reflects the degree of unmet need that the fast track designation aims to address.

VIR-5500 is currently being evaluated across 6 dose-expansion cohorts in the ongoing phase 1 study, including monotherapy cohorts in taxane-naive, radioligand therapy-naive, and radioligand therapy-exposed metastatic CRPC, as well as combination cohorts with enzalutamide in early-line metastatic CRPC, docetaxel in early-line metastatic CRPC, and darolutamide in metastatic HSPC.

References

1. Vir Biotechnology announces PSMA-targeted PRO-XTEN® dual-masked T-cell engager VIR-5500 received FDA Fast Track designation for the treatment of prostate cancer. News release. Vir Biotechnology, Inc. October 8, 2026. Accessed October 9, 2026. https://tinyurl.com/5fmc773b
2. de Bono JS, Fenor de la Maza MD, Boni V, et al. Preliminary phase 1 dose escalation results of VIR-5500 (AMX-500), a dual-masked PRO-XTEN® T-cell engager, in metastatic castration resistant prostate cancer (mCRPC). J Clin Oncol. 2026;44(suppl 7):17. doi:10.1200/JCO.2026.44.7_suppl.17