NovaBridge’s Phase 1 expansion of ragistomig, a PD-L1 × 4-1BB bispecific, reports responses in patients previously non-responsive to checkpoint inhibitors alongside an improved hepatic safety profile on a once-every-six-weeks schedule. While no response or adverse event rates were disclosed, the company says the Q6W regimen met the trial objective to extend the therapeutic window.
The new data will be detailed in a poster at ESMO-IO on December 10, covering an extended-interval dosing cohort and immunologic readouts, including CD8+ proliferation and memory T-cell activation. The study, run in the U.S. and South Korea (NCT04762641) with co-developer ABL Bio, builds on earlier dose-escalation findings and is positioned to inform subsequent combination strategies. Ragistomig uses an Fc-silent PD-L1 binder to localize activity and a 4-1BB arm for conditional T-cell costimulation, a design aimed at overcoming PD-(L)1 resistance while minimizing off-tumor activation.
Strategically, the move targets one of immuno-oncology’s harder problems: post–checkpoint inhibitor relapse where monotherapy options are sparse and combination toxicity often blunts benefit. The field’s history with 4-1BB agonism has been defined by liver toxicity and narrow dosing windows; pushing to Q6W is a clear attempt to reconcile pharmacodynamics with tolerability while maintaining engagement of memory T cells. It also fits NovaBridge’s broader bet on tumor- or target-gated 4-1BB biology, given its parallel Claudin 18.2 × 4-1BB program, by diversifying the gating mechanism (tumor antigen versus PD-L1) and broadening tumor-type reach. Against a backdrop of multiple PD-L1 × 4-1BB bispecifics in early development, the differentiation here will hinge on the balance between sustained single-agent activity and a cleaner hepatic profile at practical dosing intervals.
For sites and CROs, a Q6W infusion cadence can reduce chair time, visit frequency, and scheduling friction, which matters amid staffing constraints. If hepatic events are indeed lower at this interval, monitoring intensity and unscheduled labs could ease, although early-phase immunostimulatory agents will still demand tight safety oversight. The emphasis on pharmacodynamic biomarkers signals a trial design with dense sampling and centralized analytics, adding operational complexity but offering regulators clearer dose justification. For sponsors and investigators planning combinations, the conditional 4-1BB activation could allow layered regimens without compounding liver risk, but every add-on will test that hypothesis and reset the safety calculus.
The near-term question is whether the ESMO-IO poster provides enough granularity to validate the signal: objective response rate, duration, grade ≥3 transaminitis, discontinuations, and any exposure–response that supports Q6W as the recommended dose for expansion. Details on PD-L1 expression thresholds, tumor histologies, and prior lines will determine how broadly this can enroll in a refractory population. If single-agent activity proves modest but durable, the program likely pivots quickly to combinations; if the hepatic profile holds, partners may be willing to stack standard backbones. Watch for a Phase 2 outline with clear selection criteria, predefined liver safety stopping rules, and a biomarker plan that marries T-cell kinetics to clinical endpoints. With similar bispecifics advancing elsewhere, the bar is rising: dosing practicality, manageable monitoring, and consistent activity across sites will decide whether ragistomig earns a place in the post–checkpoint inhibitor toolkit.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
