ARX517, an antibody-drug conjugate (ADC) developed by Ambrx Biopharma, has demonstrated promising results in the APEX-01 trial, targeting metastatic castration-resistant prostate cancer (mCRPC). Recently presented data highlight ARX517’s specific action on prostate-specific membrane antigen (PSMA) in mCRPC cells, where it delivers a microtubule inhibitor payload directly into cancer cells to minimize off-target effects.

In the dose-escalation portion of APEX-01, higher dose levels (≥2.0 mg/kg) showed notable efficacy: 52% of patients experienced a PSA50 response (≥50% PSA reduction), while 26% achieved PSA90, indicating a substantial drop in PSA levels, a key biomarker for prostate cancer activity. The ADC also led to a ≥50% reduction in circulating tumor DNA (ctDNA) in 81% of evaluable patients, correlating with the reduction in cancer burden. Safety data was highly favorable, with no dose-limiting toxicities (DLTs) or severe adverse events, and only mild, manageable side effects, such as dry mouth and fatigue, were noted. These findings suggest that ARX517 has the potential to fill an unmet need for patients whose cancer has progressed despite prior treatments.

The study’s success may position ARX517 as an alternative or first-line option for mCRPC, providing hope for a population with limited treatment options. Ongoing research will further explore optimal dosing and efficacy in advanced prostate cancer stages.

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