Study launches of VIR-5500 combined with ARPIs in mCRPC

The first patient has been dosed in part 3 of a phase 1 trial (NCT05997615) assessing VIR-5500 in combination with androgen receptor pathway inhibitors (ARPIs) in patients with metastatic castration-resistant prostate cancer (mCRPC), Vir Biotechnology announced in a news release.¹

According to the company, “VIR-5500 is an investigational PRO-XTEN dual-masked T-cell engager (TCE) targeting prostate-specific membrane antigen (PSMA).”

Cohort 3 is part of the larger phase 1 trial, which is evaluating the safety, pharmacokinetics, and preliminary antitumor activity of VIR-5500 in single-agent dose escalation (part 1) and dose expansion (part 2) cohorts, as well as in combination dose escalation (part 3) and dose expansion (part 4) cohorts. Parts 1 and 2 assessed VIR-5500 in patients who had received at least one prior taxane regimen, and parts 3 and 4 will include patients in the first-line, taxane-naive setting.

“We are excited to advance our VIR-5500 phase 1 trial with the addition of early line metastatic prostate cancer cohorts exploring combination therapy," said Marianne De Backer, PhD, MSc, MBA, chief executive officer of Vir Biotechnology, in the news release.¹ “Opening part 3 of the phase 1 trial brings the potential benefits of the universal PRO-XTEN approach to patients earlier in their cancer journey, when treatment intervention may have the greatest impact on their long-term outcomes.”

The study plans to enroll a total of 390 patients across all cohorts.² The primary end points are treatment-emergent adverse events and dose-limiting toxicities in parts 1 and 3, as well as prostate-specific antigen (PSA) response rate and objective response rate in parts 2 and 4. The duration of the study is approximately 48 months.

Previous Data on VIR-5500

Interim data from parts 1 and 2 of the study were reported in January 2025.³ Overall, 18 patients had received VIR-5500 monotherapy at the time of data report, of whom 12 were included in the efficacy analysis. Participants had a range of 3 to 6 prior lines of therapy.

PSA reductions were observed in all patients (12 of 12) following an initial dose of VIR-5500 at 120 µg/kg or higher. A PSA reduction of at least 50% was confirmed in 58% of patients (7 of 12) following the first therapy dose.

Data also showed that VIR-5500 was well tolerated. No dose-limiting toxicities were reported across all dose levels, which ranged up to 1000 µg/kg without prophylactic corticosteroids. Grade 1 and 2 cytokine release syndrome (CRS) occurred in 17% and 11% of patients, respectively. No grade 3 or higher CRS was reported at any dose level. Treatment-emergent adverse events were also generally low-grade.

According to Vir Biotechnology: “No hearing loss has been reported, suggesting safety benefits of dual masking in preventing on-target, off-tumor toxicities.” Data also indicated “tumor-specific activation with minimal unmasking outside the tumor,” the company added.

At the time of the data report, a maximum tolerated dose had not been reached. The company planned to evaluate a Q3W dosing regimen due to VIR-5500’s half-life of 8 to 10 days.

“VIR-5500 has demonstrated potential as a monotherapy with PSA reductions in heavily pretreated patients early in dose escalation,” said Mark Eisner, MD, MPH, chief medical officer of Vir Biotechnology, in the news release.¹ “Building on our understanding of VIR-5500 as a monotherapy, we look forward to evaluating the potential benefit of combining the complementary mechanisms of action of VIR-5500 and ARPIs with the goal to deliver the best possible outcomes for patients.”

REFERENCES

1. Vir Biotechnology announces first patient dosed in part 3 of phase 1 trial of PSMA-targeting PRO-XTEN dual-masked T-cell engager VIR-5500 in combination with androgen receptor pathway inhibitors for the treatment of metastatic prostate cancer. News release. Vir Biotechnology Inc. October 9, 2025. Accessed October 10, 2025. https://investors.vir.bio/news/news-details/2025/Vir-Biotechnology-Announces-First-Patient-Dosed-in-Part-3-of-Phase-1-Trial-of-PSMA-Targeting-PRO-XTEN-Dual-Masked-T-Cell-Engager-VIR-5500-in-Combination-with-Androgen-Receptor-Pathway-Inhibitors-for-the-Treatment-of-Metastatic-Prostate-Cancer/default.aspx

2. Safety, pharmacokinetics, and preliminary efficacy of VIR-5500 (AMX-500) in prostate cancer. ClinicalTrials.gov. Updated September 24, 2025. Accessed October 10, 2025. https://clinicaltrials.gov/study/NCT05997615

3. Vir Biotechnology announces encouraging safety and efficacy data in ongoing dose escalation trials for dual masked T-cell engagers VIR-5818 in solid tumors and VIR-5500 in mCRPC. News release. Vir Biotechnology Inc. January 8, 2025. Accessed October 10, 2025. https://investors.vir.bio/news/news-details/2025/Vir-Biotechnology-Announces-Encouraging-Safety-and-Efficacy-Data-in-Ongoing-Dose-Escalation-Trials-for-Dual-Masked-T-Cell-Engagers-VIR-5818-in-Solid-Tumors-and-VIR-5500-in-mCRPC/default.aspx