Dr Shen on the Tolerability and Efficacy of ARX517 in mCRPC

John Shen, MD, medical oncologist, University of California Los Angeles Health Encino Cancer Care, discusses unique features associated with the use of the prostate-specific membrane antigen (PSMA)–directed antibody-drug conjugate (ADC) ARX517 in patients with metastatic castration-resistant prostate cancer (mCRPC) and highlights early efficacy and safety findings with this agent.

The ongoing, first-in-human phase 1/2 APEX-01 trial (NCT04662580) is investigating the safety and preliminary efficacy of ARX517 monotherapy in PSMA-unselected patients with mCRPC whose disease has progressed on at least two prior lines of FDA-approved treatments, with at least one being a second-generation androgen receptor pathway inhibitor, and who have met at least one of the following three criteria: PSA progression defined by a minimum of 2 rising PSA values, radiographic progression by RECIST v1.1 criteria, and/or disease progression by the presence of new bone lesions.

Across all 8 cohorts in APEX-01 (n = 65), grade 3 treatment-related adverse effects (TRAEs) were observed in 6 patients. These TRAEs included lymphocyte count decrease (n = 3), transient platelet count decrease (n = 2), and asymptomatic left ventricular dysfunction (n = 1). No treatment-related grade 3 or higher serious adverse effects occurred.

The tolerability of ARX517 is largely due to the ADC’s stable conjugation, Shen says. Previous research efforts targeting PSMA using other ADCs have been limited, and those ADCs did not progress further in clinical development because of their associated toxicities, Shen notes. Notably, the early findings from the APEX-01 trial show no such toxicity concerns associated with ARX517. Dose-escalation portions of this trial are ongoing to glean additional data regarding the safety profile of this agent, Shen explains.

Additionally, across all patients who received at least 2.0 mg/kg of the study drug, 61% achieved a prostate-specific antigen (PSA) response of 30% or greater, 52% achieved a PSA response of 50% or greater, and 26% achieved a PSA response of 90% or greater.

Although the PSA reductions of more than 50% and more than 90% are encouraging, investigators aim to determine the duration of these responses, particularly in heavily pretreated patients, according to Shen. The trial recently enrolled an additional 40 patients, and the data with these patients will be presented in the future, Shen concludes.