Biomarker And Efficacy SensitivityReliance on demonstrating activity in a difficult-to-treat cohort heightens the need for precise biomarker selection, and failure to identify responsive subgroups could constrain clinical and commercial potential.
Development Timeline RiskHigh baseline disease resistance in trial participants could necessitate larger or longer studies to achieve efficacy readouts, potentially delaying development milestones.
Patient Population RiskTargeting a heavily pretreated, biologically aggressive patient population raises the clinical risk that trials may not show meaningful responses, increasing outcome uncertainty.