VIR-5500 enters expansion cohorts in phase 1 trial for metastatic prostate cancer

The investigational prostate-specific membrane antigen (PSMA)-targeted T-cell engager (TCE) VIR-5500 has advanced into expansion cohorts in an ongoing phase 1 trial (NCT05997615) for early- and late-line metastatic prostate cancer, Vir Biotechnology announced.¹

According to the company announcement, the first patient has now been dosed in a monotherapy expansion cohort, with additional combination cohorts planned across earlier disease settings. The trial is assessing the safety and efficacy of VIR-5500 monotherapy in late-line metastatic castration-resistant prostate cancer (mCRPC) and VIR-5500 in combination with an androgen receptor pathway inhibitor (ARPI) in early-line mCRPC and metastatic hormone-sensitive prostate cancer (mHSPC).

“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, MSc, PhD, MBA, president, CEO, and director of Vir Biotechnology, said in a company news release.¹

Trial overview

VIR-5500 is a PSMA-directed bispecific TCE that binds both PSMA on tumor cells and CD3 on T cells. It incorporates a proprietary dual-masked PRO-XTEN technology that keeps the molecule inactive in circulation until it is cleaved by tumor-associated proteases within the tumor microenvironment. This masking approach aims to reduce systemic toxicity while preserving antitumor activity.

The agent is being evaluated in an open-label, nonrandomized phase 1 trial assessing its safety, pharmacokinetics, and preliminary efficacy in patients with metastatic prostate cancer. The newly initiated expansion cohort focuses on monotherapy in patients with late-line mCRPC whose disease progressed after multiple prior therapies, including at least 1 second-generation ARPI, 1 taxane-based chemotherapy regimen, and standard-of-care radioligand-based therapy.

The selected dosing regimen for expansion—step-up dosing of 800, 2000, and 3500 µg/kg every 3 weeks—was informed by earlier dose-escalation data presented at the 2026 American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium in San Francisco, California. Additional cohorts are planned to evaluate VIR-5500 in combination with enzalutamide (Xtandi) in earlier-line mCRPC and mHSPC.

Previous data on VIR-5500

Data from the dose-escalation portion of the trial (n = 58) were presented at the 2026 ASCO GU Cancers Symposium.² The study included patients with advanced mCRPC whose disease had progressed following multiple lines of therapy (median, 4 prior lines). A substantial portion of patients also presented with high tumor burden, with visceral metastases reported in nearly 50% of patients.

Overall, treatment was well tolerated, with no dose-limiting toxicities reported. Grade 3 or higher treatment-related adverse events occurred in 12% of patients and were considered manageable. Cytokine release syndrome (CRS) was observed in approximately 50% of patients, but was predominantly grade 1 and did not require routine prophylactic steroids.

Efficacy data were reported from the highest-dose cohorts (3000 µg/kg or higher every 3 weeks). Among prostate-specific antigen (PSA)-evaluable patients, PSA declines of at least 50% were observed in 82% (14 of 17) of patients, and PSA declines of at least 90% were reported in 53% (9 of 17) of patients. In RECIST-evaluable patients, the objective response rate was 45% (5 of 11), including confirmed responses in most responders (4 of 5).

“It is remarkable to see these early signs of profound antitumor activity in heavily pretreated patients [with mCRPC], and the favorable tolerability with minimal CRS to date means VIR-5500 could play a role in treating earlier disease,” Johann de Bono, MBChB, PhD, principal investigator as well as the director of the Drug Development Unit and head of the Prostate Cancer Targeted Therapy Group at The Institute of Cancer Research, said in the company release.² “For patients with metastatic prostate cancer who have long faced limited treatment choices, VIR-5500 may offer a renewed sense of hope and a potential path to better outcomes.”

The ongoing trial will expand into additional cohorts, including combination regimens with enzalutamide in earlier disease states. According to the sponsor, initiation of pivotal phase 3 trials is anticipated in 2027.

De Backer added, “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.”

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://www.businesswire.com/news/home/20260413500942/en/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

2. Vir Biotechnology reports positive updated phase 1 results for PSMA-targeting, PRO-XTEN dual-masked T-cell engager VIR-5500 in patients with metastatic prostate cancer. News release. Vir Biotechnology. February 23, 2026. Accessed April 13, 2026. https://investors.vir.bio/news/news-details/2026/Vir-Biotechnology-Reports-Positive-Updated-Phase-1-Results-for-PSMA-targeting-PRO-XTEN-Dual-masked-T-Cell-Engager-VIR-5500-in-Patients-with-Metastatic-Prostate-Cancer/default.aspx