Dual-Target ADC Shows 15-Month Progression-Free Survival in Prostate Cancer: Tanya Dorff, MD

An antibody-drug conjugate (ADC) designed to target both prostate-specific membrane antigen (PSMA) and six-transmembrane epithelial antigen of prostate-1 (STEAP1) has demonstrated a progression-free survival (PFS) signal of approximately 15 months in heavily pretreated metastatic castration-resistant prostate cancer (mCRPC)—a striking contrast to the 4- to 5-month PFS typically observed with cabazitaxel in this setting. Tanya Dorff, MD, medical oncologist at City of Hope and lead author of this study, explains how the investigational agent ABBV-969 works, what some of the notable results are, and where the program stands currently in the treatment landscape in an interview with The American Journal of Managed Care^® ahead of her presentation at the 2026 annual meeting of the American Society of Clinical Oncology.

The Dual-Target Rationale

Prostate cancer becomes increasingly heterogeneous in later disease stages, with some tumors expressing high levels of PSMA, others expressing primarily STEAP1, and many expressing both. A bispecific ADC that binds either antigen can deliver its cytotoxic payload to a broader range of tumor cell populations within the same patient, potentially reducing the resistance that emerges when single-target agents face antigen-low clones.

The agent's topoisomerase inhibitor payload differentiates it from the taxane class, which is the backbone of existing prostate cancer chemotherapy, and from the monomethyl auristatin E (MMAE) payloads used in urothelial ADCs such as enfortumab vedotin. Critically, it does not carry the peripheral neuropathy risk associated with taxanes, which is a meaningful advantage in patients who have already received prior taxane therapy.

Efficacy and Tolerability

The 15-month PFS signal and median treatment duration of approximately 296 days suggest patients can remain on therapy long enough for sustained benefit, which further reflects the treatment’s manageable tolerability. The most prominent adverse effect was anemia, with grade 3 events occurring in over 40% of patients. Dorff noted that many patients with mCRPC enter treatment already anemic due to prior radiation and bone marrow involvement; however, dose modifications and transfusions allowed most patients to continue treatment without discontinuation.

Where the Program Stands

Dose optimization is ongoing, with dose escalation having ranged from 1 mg/kg to 12.5 mg/kg. Dose-limiting toxicity was observed at 12.5 mg/kg; most efficacy data derive from patients at 3 mg/kg and above. The goal is to identify a dose that optimizes the efficacy-tolerability balance before advancing to a phase 3 trial against an existing standard-of-care comparator.