Tanya B. Dorff, MD, highlights early data on ABBV-969 in mCRPC

In the following interview, Tanya B. Dorff, MD, FASCO, discusses findings from a phase 1 dose-escalation study (NCT06318273) evaluating ABBV-969, an investigational prostate-specific membrane antigen (PSMA)/six-transmembrane epithelial antigen of the prostate-1 dual-targeting antibody drug conjugate (ADC) in patients with heavily pretreated metastatic castration-resistant prostate cancer (mCRPC). These data were presented at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois.¹

Dorff is the division chief of genitourinary oncology at City of Hope in Los Angeles, California.

Dorff explained that the study was designed to capitalize on PSMA expression in prostate cancer by using ADC technology to deliver a cytotoxic payload directly to tumor cells. While PSMA-targeted radioligand therapies have already demonstrated clinical utility in prostate cancer, ADCs offer the potential to provide a more effective and less toxic chemotherapy-like approach. The phase 1 trial employed a Bayesian-optimized dose-escalation design, evaluating doses ranging from 1 mg/kg to 12.5 mg/kg administered every 3 weeks to characterize safety and preliminary antitumor activity.

The analysis included 49 patients with mCRPC who had previously received an androgen receptor pathway inhibitor and taxane chemotherapy. The study population was heavily pretreated, with a median of 5 prior lines of therapy and substantial prior exposure to agents including docetaxel, cabazitaxel, PARP inhibitors, and lutetium-177 PSMA-targeted therapy. Patients also exhibited advanced disease characteristics, including visceral metastases in the liver (16%) and lung (14%), and bone metastases in 88% of cases.

Dorff noted that the most common adverse events were hematologic, gastrointestinal, and fatigue-related toxicities, with higher-grade events occurring more frequently at higher dose levels. Grade 3 anemia was observed in approximately 45% of patients, despite baseline hemoglobin levels already being low (median, 10.9 g/dL). Approximately one-third of patients required dose modifications, but treatment duration remained prolonged, with a median exposure of 296 days. Only 2 patients discontinued treatment because of adverse events, and cases of interstitial lung disease were limited to the highest dose level, which will not undergo further evaluation.

According to Dorff, the efficacy results were particularly encouraging given the advanced disease burden and extensive prior treatment exposure of the enrolled population. Among patients treated at doses of 3 mg/kg or higher, 67.4% achieved a PSA decline of at least 50%, with a median response duration of 10.8 months. Of the 29 patients evaluable for radiographic response, the confirmed objective response rate was 44.8%, including complete responses in 17.2% of patients and partial responses in 27.6% of patients. Median radiographic progression-free survival was 15.3 months (95% CI, 9.8 to not evaluable). Dorff noted that these outcomes are uncommon in such a heavily pretreated mCRPC population and highlighted that meaningful responses were also observed among patients with liver metastases, a subgroup that is typically associated with poor prognosis.

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