FDA grants Fast Track Designation to ARX517 for metastatic castration-resistant prostate cancer

The FDA has awarded Fast Track Designation to ARX517, an anti-prostate-specific membrane antigen (PSMA) antibody-drug conjugate (ADC) investigational therapy indicated for use in patients with metastatic castration-resistant prostate cancer (mCRPC) who experienced progression on an androgen receptor pathway inhibitor.¹

"ARX517 has the potential to be a more effective and tolerable treatment option for these patients," says Daniel J. O’Connor.

“Receiving Fast Track designation from the FDA reinforces Ambrx’s belief in ARX517 as a potential novel treatment for mCRPC and underscores the urgent need for improved treatment options for patients at this advanced stage of prostate cancer,” said Sandra Aung, PhD, in a news release.¹ Aung is the chief clinical officer of Ambrx, the developer of the therapy.

ARX517 is a PSMA targeting agent composed of fully humanized anti-PSMA mAb linked to AS269, a microtubule inhibitor. Upon binding to PSMA on the surface of tumor cells and internalizing, the therapy releases pAF-AS269 to kill the cancer cells.

The anti-PSMA ADC is currently being studied in the phase 1/2 open-label APEX-01 trial (NCT04662580). Patients enrolled in the study have mCRPC tumors that are resistant or refractory to prior standard therapies, shown by progression on at least 2 FDA-approved treatments. Participants must have also met 1 of the study criteria, which include prostate-specific antigen (PSA) progression as defined by at least 2 rising PSA values, radiographic progression as defined by RECIST v 1.1, or disease progression defined by the presence of new bone lesions.

Initial data from the trial were published earlier this year, showing promising safety and efficacy data.² Patients enrolled in the phase 1 dose escalation study received doses of ARX517 every 3 weeks. At the time of report, 22 patients in the trial had been dosed across 7 cohorts of ascending dose levels, with at least 3 patients in each cohort. The dose levels started at 0.32 mg/kg and went to 2.4 mg/kg.

The primary end points of the study were safety, tolerability, and pharmacokinetics. The secondary end point was a decline in PSA from baseline and/or tumor shrinkage.

In regard to safety, the treatment was shown to be well-tolerated. No patients experienced any drug-related severe adverse events (AEs) or treatment-related grade 3 or higher AEs at the time of report.

The data also showed a greater than 50% reduction in PSA levels from baseline among all patients in cohort 6 of the study, in which patients received doses at 2.0 mg/kg. Further, 2 of 3 patients in cohort 6 experienced a greater than 90% reduction of PSA levels. At the time of data report, the maximum tolerated dose had not yet been reached.

Further data from the study is expected to be presented later this year.

Daniel J. O’Connor, the chief executive officer of Ambrx, stated, "This Fast Track designation represents a significant milestone for Ambrx. Enabled by our expanded genetic code site-specific conjugation technology, ARX517 has the potential to be a more effective and tolerable treatment option for these patients, and we are planning to present updated preliminary data from APEX-01 at a major medical meeting this fall.”¹

References

1. FDA grants Fast Track Designation for Ambrx’s ARX517 for the treatment of metastatic castration-resistant prostate cancer. News release. Ambrx. July 19, 2023. Accessed July 20, 2023. https://ir.ambrx.com/news/news-details/2023/FDA-Grants-Fast-Track-Designation-for-Ambrxs-ARX517-for-the-Treatment-of-Metastatic-Castration-Resistant-Prostate-Cancer/default.aspx

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. February 16, 2023. Accessed July 20, 2023. https://ir.ambrx.com/news/news-details/2023/ARX517-Ambrxs-Proprietary-Anti-PSMA-ADC-Shows-Encouraging-Single-Agent-Safety-and-Efficacy-Data-in-Patients-with-Advanced-Prostate-Cancer/default.aspx