First Patient Dosed in VIR-5500 T-Cell Engager Trial in Metastatic Prostate Cancer

The first patient has been dosed in 1 of 3 expansion cohorts in the phase 1 trial (NCT05997615) evaluating VIR-5500, according to the manufacturer, Vir Biotechnology.¹

This investigational therapy is a prostate-specific membrane antigen (PSMA)–targeted, PRO-XTEN dual-masked T-cell engager intended for the treatment of metastatic prostate cancer. By utilizing a “masked” delivery system, the therapy remains inactive in the bloodstream and only becomes potent upon reaching the tumor microenvironment, a mechanism intended to increase the therapeutic window and reduce systemic adverse events.

The ongoing phase 1 trial is designed to measure the safety and efficacy of VIR-5500 monotherapy in late-line metastatic castration-resistant prostate cancer (mCRPC). Additionally, the trial evaluates VIR-5500 in combination with an androgen receptor pathway inhibitor for patients in early-line mCRPC and metastatic hormone-sensitive prostate cancer.

The monotherapy expansion cohort in late-line mCRPC is the first to begin enrollment following monotherapy dose-escalation data that showed a favorable safety profile and promising anti-tumor activity.

These data, presented at the 2026 American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO GU),² led to the selection of an 800/2000/3500 µg/kg step-up dosing regimen administered once every 3 weeks.

This cohort will monitor safety and efficacy through prostate-specific antigen response rates and objective response rates (ORR) in patients who are refractory after multiple prior therapies. Dose-escalation of VIR-5500 in combination with enzalutamide (Xtandi) also continues in early-line mCRPC patients, with first patient dosing in combination dose-expansion cohorts expected over the coming months.

“I think we’re heading toward immunotherapy that works impressively for metastatic prostate cancer with proof of concept that we can abrogate the CRS [cytokine release syndrome],” lead author Johann S. De Bono, MD, said during a presentation of the data at ASCO GU. Johann de Bono, MD, is 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. “This agent was well tolerated with minimal CRS despite not giving prophylactic steroids.”

“The initiation of the VIR-5500 expansion cohorts underscores the significant momentum behind this program and the enthusiasm we are seeing across the clinical community,” Marianne De Backer, PhD, MBA, MSc, said in a news release. De Backer is chief executive officer of Vir Biotechnology. “We are encouraged by the promising antitumor activity shown in the phase 1 data announced earlier this year and look forward to collaborating with Astellas after closing of the transaction to explore VIR-5500’s potential to make a meaningful difference across the spectrum of metastatic prostate cancer.”

Background About Phase 1 Trial

The objectives of the study were to characterize safety, pharmacokinetics profiles, and antitumor activity. Fifty-one heavily pretreated patients with mCRPC received 1 or more doses of VIR-5500. No dose-limiting toxicities were reported. The incidence of related grade 3 or higher adverse events was low and CRS was limited to grade 1 and 2. Investigators reported an ORR of 67% in 4 out of 6 RECIST-evaluable patients.

About VIR-5500

T-cell engagers are potent antitumor therapies that harness the immune system to target and eliminate cancer cells. VIR-5500 is an investigational PRO-XTEN dual-masked T-cell engager under evaluation in an open-label, nonrandomized phase 1 trial, and is the only PSMA-directed agent of its kind currently in clinical development.

This dual-masking approach is designed to limit activity to the tumor microenvironment, potentially reducing the toxicity seen with unmasked engagers while improving efficacy and tolerability. Additionally, the masking strategy may prolong circulation time in an inactive state, supporting the possibility of less frequent dosing.

REFERENCES

1. Vir Biotechnology Announces First Patient Dosed in Phase 1 Dose-expansion Cohorts Evaluating PSMA-targeted, PRO-XTEN Dual-masked T-cell Engager VIR-5500 in Patients with Metastatic Prostate Cancer. News release. Vir Biotechnology. April 13, 2026. Accessed April 13, 2026. https://tinyurl.com/ytkftekx

2. DeBono JS, De La Maza DF, Boni V, et al. Preliminary phase 1 dose escalation results of VIR-5500 (AMX-500), a dual masked PRE-XTEn T-cell engager, in metastatic castration resistant prostate cancer (mcRPC). J Clin Oncol. 2026;44(suppl 7):abstract 17. doi:10.1200/JCO.2026.447_suppl.17