Breast Cancer Coverage from Every Angle

Early-Phase Trials of Novel Antibody-Drug Conjugate in HER2-Overexpressed Solid Tumors

By: Julia Fiederlein
Posted: Wednesday, July 21, 2021

According to Sara A. Hurvitz, MD, of the University of California, Los Angeles, and colleagues, the high stability of the site-specific antibody-drug conjugate ARX788 and low serum exposure of its metabolite, para-acetylphenylalanine (pAF)-AS269, may underlie the low systemic toxicity of this agent in heavily pretreated patients with HER2-overexpressing solid tumors. The pooled safety and pharmacokinetic analyses from two phase I trials were presented during the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract 1038).

The ACE-Breast-01 (n = 69) and ACE-Pan tumor-01 (n = 34) trials enrolled patients with HER2-positive breast cancers and solid tumors, respectively; they were administered ARX788 in doses ranging from 0.33 to 1.5 mg/kg. The serum pharmacokinetic profiles of ARX788, total antibody, and pAF-AS269 were characterized.

No dose-limiting toxicities were reported. The maximum tolerated dose was not reached. Most adverse events were grade 1 or 2. In the ACE-Breast-01 trial, ocular adverse events (5.7%) and pneumonitis (4.3%) were among the most frequently reported side effects of higher than grade 3; pneumonitis (2.9%) and fatigue (2.9%) were reported most commonly in the ACE-Pan tumor-01 trial. No treatment-related deaths were reported.

The objective response rates were 74% and 67% in the 1.5-mg/kg cohorts of the ACE-Breast-01 and ACE-Pan tumor-01 trials, respectively. The disease control rate was 100%. The median durations of response and progression-free survival were not reached.

Generally, the pharmacokinetic profiles for total antibody and ARX788 were comparable across all dose levels. At a dose of 1.5 mg/kg, the mean half-life for ARX788 and total antibody was approximately 100 hours. The serum levels of pAF-AS269 reached a peak concentration at a median of 168 hours. The serum exposure of pAF-AS269 was low; the maximum serum concentration and AUC at cycle one were approximately 0.1% and 0.18% of those for ARX788 on a molar basis, respectively.

Disclosure: For full disclosures of the study authors, visit

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