AMAM - Ambrx Announces ARX517 a PSMA-Targeted ADC Demonstrates a Promising 52% PSA50 (?50% Reduction) and a Highly Differentiated Safety and PK Profile in Patients with mCRPC who Progressed on Multiple FDA-Approved Treatments | Benzinga

Newly published data from the Phase 1 portion of the on-going
Phase 1 / 2 APEX-01 trial provide the following key points:

• Multiple efficacy endpoints demonstrate consistent and promising anti-cancer activity at therapeutic doses of 2.0 – 2.88 mg/kg (Cohorts 6-8) in heavily pretreated patients (median of 4 and maximum of 13 prior lines of therapy):
  
  
  • 52% (12/23) of patients experienced a ?50% PSA reduction
    
  • 81% (17/21) of patients experienced ?50% circulating tumor DNA reduction
  • 50% (3/6) of patients with prior PSMA-targeted radionuclide therapy (TRT) experienced a ?50% PSA reduction
  • 50% (2/4) experienced a >30% reduction in target lesion(s)
    
• A strong and highly differentiated safety profile observed across 65 patients at all dose levels with no treatment-related SAEs or DLTs
  

SAN DIEGO, Oct. 23, 2023 (GLOBE NEWSWIRE) -- Ambrx Biopharma, Inc., or Ambrx, (NASDAQ:AMAM), today announced that in biomarker unselected patients ARX517 monotherapy demonstrated a strong antibody-drug conjugate (ADC) safety profile at all doses tested with promising early efficacy signals that included PSA50 declines, ctDNA reductions, and RECIST v1.1 tumor response. The ESMO clinical posters present updated safety, efficacy and PK data from Ambrx's on-going trial, APEX-01 (NCT04662580).   Posters were made available as part of the 2023 European Society for Medical Oncology (ESMO) Congress 2023 meeting, taking place in Madrid, Spain, October 20-24, 2023, and are summarized below.

APEX-01 is a Phase 1 / 2, first-in-human, open label dose escalation and dose expansion trial enrolling patients with metastatic castration-resistant prostate cancer (mCRPC). To be eligible for APEX-01, patients with mCRPC had to satisfy certain criteria, including receiving at least two prior FDA-approved therapies for metastatic disease, with at least one being a 2^nd generation androgen receptor pathway inhibitor (ARPI), and who have met at least one of the following three criteria: PSA progression defined by a minimum of two rising PSA values, radiographic progression by RECIST v1.1, and/or disease progression by the presence of new bone lesions.

APEX-01 opened for enrollment in July 2021 and is the only on-going clinical trial in the United States targeting PSMA with an ADC. The two primary objectives of APEX-01 are to analyze the safety and tolerability of ARX517 and establish a recommended Phase 2 dose.

Dr. John Shen, a medical oncologist at UCLA and an investigator on APEX-01, stated that, "The PSA results are very encouraging especially in this heavily pre-treated patient population where eligible patients would have exhausted all available and appropriate treatment options prior to enrolling in this study."

Data Highlights

As of the data cutoff date (September 5, 2023), highlights from the safety and efficacy data are summarized below:

• Deep PSA reductions have been seen with increasing ARX517 dose. PSA reductions deepened as dose levels increased, demonstrating a dose dependent PSA reduction:
  
  • ?50% PSA reduction observed in 25% (4/16) and 50% (7/14) of patients at 1.4 mg/kg (Cohort 4) and 2.0 mg/kg (Cohort 6), respectively
  • ?90% PSA reduction observed in 6% (1/16) and 36% (5/14) of patients at 1.4 mg/kg (Cohort 4) and 2.0 mg/kg (Cohort 6), respectively
• Multiple coinciding efficacy endpoints demonstrate a consistent and promising anti-cancer activity at therapeutic doses of 2.0 – 2.88 mg/kg (Cohorts 6-8):
  
  • 52% (12/23) patients experienced a ?50% PSA reduction
    
    • 7 of 14 patients at 2.0 mg/kg (Cohort 6)
    • 3 of 6 patients at 2.4 mg/kg (Cohort 7)
    • 2 of 3 patients at 2.88 mg/kg (Cohort 8)
  • 81% (17/21) patients experienced a ?50% ctDNA reduction
  • 50% (2/4) experienced a >30% reduction in target lesion(s), one of which had a reduction in liver and lung lesions

Regarding the recent data, Dr. ...

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