AbbVie’s ABBV-969, a dual-targeting antibody-drug conjugate aimed at both PSMA and STEAP1 on prostate cancer cells, produced biomarker responses in a Phase 1 dose escalation study in metastatic castration-resistant prostate cancer, according to data AbbVie summarised ahead of its ESMO presentation. Among 49 heavily pretreated patients, with a median of five prior lines of therapy, 90 percent achieved a reduction of at least 50 percent in circulating tumor DNA by cycle three, and 78 percent converted their circulating tumor cell counts from unfavourable to favourable levels.
Among 27 patients with baseline PSMA imaging who received doses of at least 3 mg/kg, two were PSMA-negative by the criteria used in the VISION trial; both achieved a PSA50 response, one with stable disease and one with a confirmed partial response. AbbVie presents that detail as support for the dual-target design: a drug that also binds STEAP1 may reach tumour cells that a PSMA-only agent would miss.
The evidentiary limits are plain. These are biomarker findings from a dose escalation study, released by the sponsor in a congress preview on October 18, not response or survival results from a controlled trial. Circulating tumor DNA clearance is a promising pharmacodynamic signal and is increasingly used to triage ADC programs, but it is not a validated substitute for progression-free or overall survival in prostate cancer.
What the data do is keep ABBV-969 in development with a rationale that is testable: if dual targeting truly addresses heterogeneity, later cohorts should show imaging and PSA responses in PSMA-low patients at rates single-target agents do not. That, not the biomarker percentage, is the readout to wait for.