Ambrx Biopharma Inc., or Ambrx, (NYSE: AMAM) today announced encouraging initial data from its ongoing Phase 1 trial (APEX-01 (NCT04662580)) investigating ARX517, Ambrx's proprietary anti-PSMA ADC, in prostate cancer patients. APEX-01 is a Phase 1, first-in-human, open label dose escalation and dose expansion trial enrolling patients with advanced prostate cancer whose tumors have progressed on at least two prior FDA-approved treatments. APEX-01 is the only ongoing clinical trial in the United States targeting PSMA with an ADC. APEX-01 opened for enrollment July 2021 and this is the first data being reported in the study.
In the Phase 1 dose-escalation portion of the study, ascending dose levels of ARX517 is administered as a single agent every 3 weeks. The primary endpoints are safety, tolerability and pharmacokinetics. The key secondary endpoint is objective decline of prostate-specific antigen (PSA) from baseline and/or tumor shrinkage. PSA is a protein produced by the prostate gland and is commonly used as a biomarker to diagnose and follow prostate cancer. A greater-than or equal to 50% reduction in PSA levels from baseline is considered clinically relevant and has been shown to correlate with improved overall survival in prostate cancer.
To date, 22 prostate cancer patients have been dosed across 7 dose level Cohorts starting from 0.32 mg/kg to 2.4 mg/kg. A minimum of 3 patients were enrolled at each Cohort. The dose limiting toxicity (DLT) period is 21 days.
Of 22 patients evaluable for safety, no drug-related severe adverse events (SAEs) or grade greater-than or equal to3 treatment-related AEs have been observed. ARX517 was well-tolerated with grade 1 or 2 treatment-related adverse events being reported. The maximum tolerated dose (MTD) has not yet been reached.PSA reductions of > 30% have been observed in Cohorts 2-5, beginning at the second to lowest dose, 0.64 mg/kg.In Cohort 6 (2.0 mg/kg dose), 3 of 3 (100%) patients experienced a greater than 50% reduction in PSA levels. 2 of 3 patients experienced a greater than 90% reduction of PSA levels. One of three patients had soft tissue measurable disease and experienced a RECIST v1.1 partial response at the first on-treatment scan.Three patients have been dosed in Cohort 7 with no DLTs.
"The preliminary data from patients with prostate cancer are highly encouraging," said Dr. Michael Schweizer, MD, an Investigator on APEX-01 and Associate Professor
Division of Medical Oncology, Fred Hutchinson Cancer Research Center. "Seeing a greater than 50% reduction in PSA levels in three of three patients at the 2.0 mg/kg dose level in this patient population is impressive, and ARX517 appears to be well tolerated so far. I am very optimistic for its future development. We look forward to more data from APEX-01, as the dose escalation continues in this difficult-to-treat patient population."
The Safety Monitoring Committee (SMC) meeting to discuss the next dose Cohort is scheduled for the end of February 2023. Not all patients have undergone or completed tumor assessments and the data are not yet final.
Ambrx plans to report further information regarding ARX517 and the APEX-01 study at its upcoming Analyst and Investor Day scheduled for February 24, 2023. Additional data are planned for presentation at an upcoming medical meeting.
