Vir Biotechnology has announced encouraging initial Phase 1 data for its dual-masked T-cell engagers (TCEs), VIR-5818 and VIR-5500, in patients with solid tumors. The data, presented on January 8, 2025, reveal promising safety and efficacy profiles, suggesting a potential advancement in cancer immunotherapy.
VIR-5818: Targeting HER2-Expressing Solid Tumors
VIR-5818 is designed to target a variety of HER2-expressing solid tumors, including breast and colorectal cancer (CRC). The Phase 1 clinical trial (NCT05356741) is evaluating its safety and pharmacokinetics, both as a monotherapy and in combination with pembrolizumab. The study has enrolled 79 heavily pretreated participants.
Early efficacy data indicate that 50% (10/20) of participants receiving VIR-5818 doses ≥400 µg/kg experienced dose-dependent tumor shrinkage across multiple HER2-positive tumor types. Notably, in a subset of participants with HER2-positive CRC who had exhausted standard of care, confirmed partial responses (cPRs) were observed in 33% (2/6) of participants at early doses, with one patient continuing in cPR for more than 18 months as of the data cut-off.
Preliminary safety data demonstrate that VIR-5818 is generally well-tolerated, with minimal grade 1 or 2 cytokine release syndrome (CRS) (20% and 10%, respectively) and no grade 3 or greater CRS observed in any of the 79 participants across doses up to 1000 µg/kg. Most treatment-emergent adverse events (TEAEs) were low grade, reversible, and manageable. The maximum tolerated dose (MTD) has not yet been reached. The dual masking results in a half-life of approximately 6 days, which may enable a less frequent dosing regimen, with Vir Biotechnology currently evaluating a Q3W dosing regimen.
VIR-5500: Targeting PSMA in Metastatic Castration-Resistant Prostate Cancer (mCRPC)
VIR-5500 is being evaluated in a Phase 1 clinical trial (NCT05997615) designed to assess its safety, pharmacokinetics, and preliminary efficacy in participants with mCRPC. The study has enrolled 18 participants with significant disease burden who have received 3 to 6 prior lines of therapy.
Early efficacy data show encouraging signs of prostate-specific antigen (PSA) responses, with PSA reductions observed in 100% (12/12) of participants after an initial dose ≥120 µg/kg. A PSA50 response was confirmed in 58% (7/12) of participants receiving a first dose ≥120 µg/kg.
Preliminary data show a promising safety profile, with no dose-limiting toxicities observed up to 1000 µg/kg without prophylactic corticosteroids. Safety findings showed minimal grade 1 or 2 CRS (17% and 11%, respectively) and no grade 3 or greater CRS at any dose. Most TEAEs were low grade. No hearing loss has been reported, suggesting safety benefits of dual masking in preventing on-target, off-tumor toxicities. Dose escalation is ongoing, and the MTD for VIR-5500 has not yet been reached. The dual-masked TCE shows a desirable half-life of 8-10 days, which is enabling Vir Biotechnology to evaluate a Q3W dosing regimen.
PRO-XTEN™ Masking Technology
Both VIR-5818 and VIR-5500 leverage the PRO-XTEN™ masking technology, which is designed to keep the TCEs inactive until they reach the tumor microenvironment. This selective activation aims to circumvent the traditionally high toxicity associated with TCEs and increase their efficacy and tolerability. Marianne De Backer, M.Sc., Ph.D., MBA, Chief Executive Officer, Vir Biotechnology, stated, "Overcoming the toxicity-driven limitations of traditional T-cell engagers could address an important unmet medical need in cancer care."
With dose escalation ongoing for both VIR-5818 and VIR-5500, Vir Biotechnology is optimistic about the potential of these dual-masked T-cell engagers to provide efficacious and well-tolerated treatment regimens for patients with various solid tumors.
