Vir Biotechnology is presenting initial Phase 1 data from its dual-masked T-cell engagers (TCEs): VIR-5818, which targets a variety of HER2-expressing solid tumors, and VIR-5500, which targets PSMA in metastatic castration-resistant prostate cancer (mCRPC). The data indicates encouraging preliminary safety and efficacy, with the maximum tolerated dose (MTD) not yet reached as dose escalation continues, and early clinical response signals observed in heavily pretreated participants. These initial results provide clinical support for Vir Biotechnology's in-licensed PRO-XTEN masking technology, which is designed to enable the selective activation of TCEs in the tumor microenvironment, mitigating damage to healthy cells and reducing toxicity.
VIR-5818: Potential First-in-Class HER2 Immunotherapy
Despite the availability of HER2-targeting therapies, there remains a significant unmet need for HER2-directed therapies with novel mechanisms of action to improve tolerability and extend survival. Currently, no HER2-directed immunotherapies are approved for solid tumors. The preliminary safety and efficacy data from the VIR-5818 Phase 1 trial supports the selective activation of PRO-XTEN dual-masked TCEs and the potential of this technology to broaden the therapeutic index of TCEs.
The Phase 1 clinical trial (NCT05356741) is designed to study the safety and pharmacokinetics of VIR-5818 alone and in combination with pembrolizumab in participants with a variety of HER2-expressing cancers, including breast and colorectal cancer (CRC). The study has enrolled 79 heterogeneous and heavily pretreated participants in monotherapy cohorts.
Early efficacy data shows that participants receiving doses ≥400 μg/kg experienced dose-dependent tumor shrinkage across multiple HER2-positive tumor types. This includes participants who had received up to 9 prior lines of therapy. Strong anti-tumor activity was observed in a subset of participants with HER2-positive CRC who have exhausted standard of care. In this subset, confirmed partial responses (cPR) or confirmed complete responses (cCR) were observed in a subset of participants at early doses, and one patient continued in cPR for more than 18 months as of the data cut-off.
VIR-5500: Targeting PSMA in mCRPC
VIR-5500 is designed to target PSMA in metastatic castration-resistant prostate cancer (mCRPC). Early data suggests a manageable safety profile, with dose escalation ongoing to determine the maximum tolerated dose and optimal therapeutic window. Further studies are planned to assess the efficacy and safety of VIR-5500 in a larger patient population.
