Dr Pachynski on the Ongoing Investigation of ARX517 in Advanced Solid Tumors

Russell Pachynski, MD, associate professor of medicine, Division of Medical Oncology, Washington University School of Medicine in St Louis, medical oncologist, Siteman Cancer Center, discusses the ongoing investigation of ARX517 in patients with advanced solid tumors, including prostate cancer, in the phase 1/2 APEX-01 trial (NCT04662580).

ARX517 is a novel anti–prostate-specific membrane antigen (PSMA) antibody-drug conjugate comprised of a humanized anti-PSMA monoclonal antibody linked to 2 proprietary microtubule-disrupting toxins (AS269). A first-in-human, multicenter study is currently assessing the safety, pharmacokinetics, and preliminary anti-tumor efficacy of the agent as a monotherapy in patients with advanced solid tumors whose disease has responded to standard therapies, including patients with metastatic castration-resistant prostate cancer (mCRPC), Pachynski details.

In this study, ascending dose levels of ARX517 are administered every 3 weeks. To date, the trial has evaluated 22 patients with prostate cancer distributed across 7 dose level cohorts ranging from 0.32 mg/kg to 2.4 mg/kg, with a minimum of 3 patients in each cohort. The dose limiting toxicity (DLT) assessment period is 21 days.

Initial clinical findings from the phase 1 dose escalation portion of the trial showed that all 3 patients in cohort 6 with metastatic prostate cancer, who received ARX517 at 2.0 mg/kg, experienced a substantial reduction in prostate-specific antigen (PSA) levels, Pachynski reports. PSA was reduced by more than 50% in all 3 patients, with 2 patients experiencing a PSA reduction of over 90%. Importantly, no severe adverse effects (AEs) or dose-limiting toxicities (DLTs) related to the drug were reported, indicating a favorable safety profile, Pachynski states. Based on this safety profile, ARX517 may be more tolerable for this population than prior ADCs due to its unique design and chemical interactions, he notes.

Overall, early results demonstrate the potential efficacy of ARX517 in reducing PSA levels and its tolerability in patients with metastatic prostate cancer, Pachynski concludes. The dose-escalation study is ongoing and continues to enroll patients.