No serious adverse events or dose-limiting toxicities were observed in the phase 1/2 trial of the antibody drug conjugate ARX517.
ARX517, an anti-prostate specific membrane antigen (PSMA) antibody drug conjugate (ADC), demonstrated positive safety and efficacy following the 21-day dose-limiting toxicity (DLT) observation period in the phase 1/2 APEX-01 trial (NCT04662580) in metastatic castration-resistant prostate cancer (mCRPC).1
Two of 3 patients receiving 3.4 mg/kg of ARX517 had prostate specific antigen (PSA) reductions of 91% and 33% at 3 weeks after receiving 1 dose. The third patient in the cohort had non-PSA secreting mCRPC. The 3.4 mg/kg dose also exhibited no DLTs or serious adverse events (SAEs).
The dosing will now expand to 4.5 mg/kg. The 1.4 mg/kg, 2.0 mg/kg, and 2.88 mg/kg cohorts are fully enrolled.
“We continue to observe no DLTs or SAEs at the highest ARX517 dose tested. We believe this is a direct result of the stability of conjugation supported by [pharmacokinetic] data presented at [the European Society of Medical Oncology Annual Congress] last month. While we are opportunely positioned to explore higher doses, we have already observed significant PSA50 decline and long duration on treatment at 2.0 mg/kg,” said Sandra Aung, PhD, chief clinical officer of Ambrx, in a press release.
APEX-01 is a phase 1/2 trial assessing the safety and tolerability of ARX517 as a single agent or in combination with enzalutamide (Xtandi) in the treatment of patients with mCRPC. The primary end point is incidence of SAEs, and the secondary end points include overall survival, progression-free survival, and changes in serum PSA levels.2
To be eligible to participate, patients must have documented metastatic prostate adenocarcinoma, castration-resistant prostate cancer with serum testosterone levels of ≤ 50 ng/dL (1.73 nM), previously received at least 2 lines of treatment, and adequate blood counts. Patients are not eligible to participate If they have symptomatic or untreated central nervous system metastases, a history of invasive malignancy within 2 years of enrollment, a history of interstitial lung disease, or marked baseline QT prolongation.
The trial has an estimated total enrollment of 222 patients. It began in July 2021 and has an estimated completion date of March 2027.
“The high interest in our PSMA-targeting ADC and pace of enrollment in the APEX-01 study has been outstanding and based on this we are anticipating to reach a recommended phase 2 dose by early next year,” Aung added, in a press release.1