FDA Gives Fast Track Designation to ARX517 in Metastatic CRPC

Investigators are currently assessing ARX517 in the phase 1/2 APEX-01 trial (NCT04662580) among patients with metastatic CRPC with disease progression after a minimum of 2 FDA-approved therapies for prostate cancer.

The FDA has granted fast track designation to ARX517 for managing metastatic castration-resistant prostate cancer (CRPC) that has progressed following treatment with an androgen receptor pathway inhibitor, according to a press release from Ambrx Biopharma Inc.¹

Investigators are currently assessing ARX517 in the phase 1/2 APEX-01 trial (NCT04662580) among patients with metastatic CRPC with disease progression after a minimum of 2 FDA-approved therapies for prostate cancer. The agent will be administered to patients with at least 1 of the following disease characteristics: prostate-specific antigen (PSA) progression or a minimum of 2 rising PSA values, radiographic progression per RECIST v1.1 criteria, or disease progression based on the appearance of new bone lesions.

“Receiving fast track designation from the FDA reinforces Ambrx’s belief in ARX517 as a potential novel treatment for [metastatic] CRPC and underscores the urgent need for improved treatment options for patients at this advanced stage of prostate cancer,” Sandra Aung, PhD, chief clinical officer at Ambrx, said in the press release.

According to preclinical data from the phase 1 dose-escalation portion of the APEX-01 study published in February 2023, ARX517 elicited no treatment-related severe adverse effects (SAEs) of grade 3 or higher or high-grade treatment-related AEs among 22 patients who were evaluable for safety.² Additionally, there were PSA reductions of more than 30% across 4 of 7 dosing cohorts starting at the second-lowest dose of 0.64 mg/kg.

In the 2.0 mg/kg dosing cohort, all 3 patients had a PSA level reduction of higher than 50%, and 2 of 3 patients had a greater than 90% reduction. Moreover, 1 patient in this cohort had a partial response as observed in the first on-treatment scan.

“The preliminary data from patients with prostate cancer are highly encouraging,” study investigator Michael Schweizer, MD, an associate professor of the Division of Medical Oncology at Fred Hutchinson Cancer Research Center, said in a press release at the time these data were published. “We look forward to more data from APEX-01, as the dose escalation continues in this difficult-to-treat patient population.”

The investigational antibody-drug conjugate ARX517 consists of a fully humanized monoclonal antibody that binds to the prostate-specific membrane antigen on the surface of cancer cells, which releases its cancer killing payload, pAF-AS269, after lysosomal metabolism. It is hypothesized that the agent may promote highly specific tumor cell killing while reducing off-target toxicity.

In the multi-center, open-label phase 1/2 APEX-01 trial, patients will receive ascending dose levels of ARX517 intravenously every 3, 4, or 6 weeks. Across 7 cohorts, patients will receive doses ranging from 0.32 mg/kg to 2.4 mg/kg.

The trial’s primary end point is the incidence of AEs. Secondary end points include the maximum serum concentration, overall survival, changes in PSA levels, and progression-free survival.

Patients 18 years and older with histologically confirmed prostate adenocarcinoma and documented metastatic disease are eligible for enrollment on the trial. Additional eligibility criteria include having CRPC based on Prostate Cancer Working Group 3 criteria and adequate blood counts. Those with central nervous system metastases or a history of any invasive malignancy within 2 years of study entry are unable to enroll on the study.

References

1. FDA grants fast track designation for Ambrx’s ARX517 for the treatment of metastatic castration-resistant prostate cancer. News release. Ambrx Biopharma Inc. July 19, 2023. Accessed July 20, 2023. bit.ly/43tOQrb
2. ARX517, Ambrx’s proprietary anti-PSMA ADC, shows encouraging single-agent safety and efficacy data in patients with advanced prostate cancer. News release. Ambrx Biopharma Inc. February 16, 2023. Accessed July 20, 2023. bit.ly/3Y6E7BW