The FDA granted fast track designation to the PSMA-targeted T-cell engager VIR-5500 for late-line metastatic castration-resistant prostate cancer.
The FDA has granted fast track designation to VIR-5500 (AMX-500), an investigational prostate-specific membrane antigen (PSMA)–targeted, dual-masked T-cell engager, for the treatment of patients with late-line metastatic castration-resistant prostate cancer (mCRPC).¹
VIR-5500 is currently being evaluated in a phase 1 trial (NCT05997615) in patients with progressive mCRPC. Previously reported findings from the dose-escalation portion of the study showed that VIR-5500 was generally well tolerated and demonstrated preliminary antitumor activity in patients with mCRPC.1,2 Findings showed no dose-limiting toxicities were reported, and grade 3 or higher treatment-related adverse effects (TRAEs) occurred in 12% of evaluable patients (n = 58).2 Cytokine release syndrome (CRS) was reported in 50% of patients, although these events were generally grade 1.
Efficacy data showed that in evaluable patients treated with a dose of at least 3000 µg/kg (n = 17), PSA level decreases of at least 50% occurred in 82% of patients, and decreases of at least 90% were observed in 45% of patients. In those evaluable for response per RECIST 1.1 criteria (n = 11), the objective response rate (ORR) was 45%, with 4 of the 5 responses confirmed.
Vir Biotechnology and Astellas Pharma, who are codeveloping VIR-5500, anticipate initiating phase 3 trials in 2027.
“Receiving fast track designation reflects the potential of VIR-5500 to address an area of serious unmet need in late-line mCRPC and the strong momentum we have achieved with Astellas as we prepare to enter pivotal phase 3 development in 2027,” Marianne De Backer, MSc, PhD, MBA, president and chief executive officer of Vir Biotechnology, stated in a news release.1 “We look forward to working with the FDA to rapidly advance the development of VIR-5500 for people living with mCRPC.”
VIR-5500 is designed to bind PSMA on tumor cells and CD3 on T cells via the PRO-XTEN masking platform, intended to limit activity outside the tumor microenvironment. Once in the tumor microenvironment, tumor-associated proteases cleave the masks, activating the T-cell engager and enabling T cells to attack PSMA-expressing cancer cells.
The masks are also intended to extend the molecule’s circulation time while it remains inactive. By concentrating activation within tumors, the platform aims to reduce toxicity and widen the therapeutic window, potentially supporting less frequent dosing.
The ongoing, first-in-human, open-label, nonrandomized phase 1 study is assessing the safety, pharmacokinetics, and preliminary efficacy of VIR-5500.3 The protocol includes monotherapy dose escalation and expansion, followed by combination dose escalation and expansion with an orally administered androgen receptor pathway inhibitor. Dosing in the dose-expansion cohorts began in April 2026.4
Six dose-expansion cohorts are evaluating VIR-5500 across different treatment settings.1 Monotherapy cohorts include patients with mCRPC who are taxane naive, radioligand therapy naive, or previously exposed to radioligand therapy. Combination cohorts are investigating VIR-5500 with enzalutamide (Xtandi) or docetaxel (Taxotere) in early-line mCRPC, and with darolutamide (Nubeqa) in metastatic hormone-sensitive prostate cancer.¹
Eligibility for the monotherapy dose-escalation cohorts includes documented progressive mCRPC following at least one second-generation androgen signaling inhibitor and at least one taxane regimen, with patients considered unsuitable for standard treatment.3
VIR-5500 is administered by intravenous infusion in 21- or 28-day cycles.
Primary end points in the dose-escalation portions include the incidence of dose-limiting toxicities and TRAEs. In the dose-expansion portions, primary efficacy end points include PSA response rate and ORR. Treatment-emergent antidrug antibodies are also being assessed across the study.
Secondary end points include duration of response, progression-free survival, pharmacokinetic parameters, and additional safety and immunogenicity assessments.
“People living with advanced prostate cancer need new treatment options that can offer meaningful and durable benefit,” Moitreyee Chatterjee-Kishore, executive vice president and head of Oncology Development at Astellas, added in a news release.1 “This fast track designation reinforces the importance of advancing VIR-5500 with urgency, and we are committed to exploring its potential to make a meaningful difference for patients and their families.”
