FDA Grants Fast Track Designation to ARX517 for mCRPC


Initial data from the phase 1/2 APEX-01 trial support the FDA’s fast track designation for ARX517 in patients with metastatic castration-resistant prostate cancer.

The FDA has granted a fast track designation to ARX517 for the potential treatment of patients with metastatic castration-resistant prostate cancer (mCRPC) who experience disease progression on an androgen receptor (AR) pathway inhibitor.1

ARX517 is an antibody-drug conjugate (ADC) made of a fully humanized anti–prostate-specific membrane antigen (PSMA) monoclonal antibody which is linked to AS269. ARX517 binds to PSMA on the surface of cancer cells, is internalized, and then its payload, pAF-AS269, is released following lysosomal metabolism.

Currently, the ongoing phase 1/2 APEX-01 trial (NCT04662580) is evaluating the agent in patients with mCRPC.2 According to initial data from the study, the ADC, when given at doses starting at 0.32 mg/kg, led to prostate-specific antigen (PSA) reductions that were greater than 30% in cohorts 2 to 5.3

In cohort 6, all 3 patients treated with ARX517 at 2.0 mg/kg had reductions in PSA levels greater than 50%. Two patients had a reduction of greater than 90%. One of the 3 patients with soft tissue measurable disease achieved a partial response to treatment according to RECIST v1.1 at the time of their first scan. At this same time, cohort 7 had administered 3 patients the ADC, and no dose-limiting toxicities were observed.

Further, no drug-related severe adverse events (SAEs) or grade ≥3 treatment-related adverse events (TEAEs) were observed among the 22 patients evaluable for safety. Overall, these findings showed that ARX517 was well-tolerated with grade 1 or 2 TRAEs reported, and the maximum tolerated dose (MTD) had not yet been reached.

“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, chief clinical officer of Ambrx Biopharma, Inc., in a press release.

In the open-label, dose-escalation, dose-expansion APEX-01 trial, patients aged 18 years and older with mCRPC are being enrolled if their tumors have progressed on 2 or more FDA-approved treatments for metastatic disease, including 1 AR receptor signaling inhibitor, metastatic disease, and adequate blood counts.

The phase 1 portion of the study administered ARX517 at escalating doses given every 3, 4, or 6 weeks. The dose-expansion period of the study will then give patients doses at or below the MTD, identified as the putative recommended phase 2 dose.

Primary end points of the study include safety, tolerability, and pharmacokinetics with the key secondary end point of the study being decline in PSA from baseline and/or tumor shrinkage. An at least 50% reduction in PSA levels was correlated with improved survival in this population.3

"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,” said Daniel J. O'Connor, chief executive officer of Ambrx, in a press release.1

  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 21, 2023. https://tinyurl.com/4c3t3ren
  2. ARX517 in subjects with metastatic castration-resistant prostate cancer (ARX517). ClinicalTrials.gov. Updated May 6, 2023. Accessed July 21, 2023. https://classic.clinicaltrials.gov/ct2/show/NCT04662580
  3. 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 21, 2023. https://tinyurl.com/f743yzfk
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