UPDATE: ABBV-969 Shows Strong Molecular Responses in Advanced Prostate Cancer

New biomarker data provide additional evidence of the preliminary activity of ABBV-969, an investigational antibody-drug conjugate (ADC) designed to target both PSMA and STEAP1 in metastatic castration-resistant prostate cancer (mCRPC).

The findings come from the ongoing Phase 1 study, involving 49 heavily pretreated patients who had received a median of five previous treatment lines. Most had already undergone chemotherapy, and more than half had received PSMA-targeted radioligand therapy.

Unlike previous analyses focusing on PSA declines and tumor responses, this update examines molecular changes associated with treatment, including circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), and tumor biomarker expression.

At the beginning of treatment, all patients with evaluable tumor biopsies showed detectable PSMA and STEAP1 expression. Despite considerable variation in their genetic alterations, substantial molecular responses were observed:

• 90% of evaluable patients experienced a reduction of at least 50% in ctDNA by the beginning of the third treatment cycle.
• 57% achieved a ctDNA reduction of at least 95%.
• 78% of patients with elevated baseline CTC counts experienced a reduction below the threshold of five cells.
• 47% achieved complete CTC clearance.

One particularly interesting observation involved two patients whose PSMA-PET scans were classified as negative according to the criteria used in the VISION trial. Both achieved a PSA reduction of at least 50%. One had stable disease, while the other achieved a confirmed partial radiological response.

These findings are consistent with the rationale behind ABBV-969: targeting two different prostate cancer surface proteins could potentially help overcome differences in target expression between tumors and individual cancer cells.

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