A phase I study recently published on Clinical Cancer Research shows safety and antitumor activity of ARX788, a novel antibody–drug conjugate, in patients with HER2-positive metastatic breast cancer.
ARX788 is a novel antibody–drug conjugate comprised of an anti-HER2 monoclonal antibody and a potent tubulin inhibitor payload AS269 that is site-specifically conjugated to the antibody via a nonnatural amino acid incorporated into the antibody. Authors involved 69 patients with metastatic breast cancer who received ARX788 at different doses every 3 or 4 weeks. No dose-limiting toxicity or drug-related deaths occurred. Most patients experienced at least one treatment-related adverse event and the common ones (≥ 30%) included an increase in aspartate aminotransferase, an increase in alanine aminotransferase, corneal epitheliopathy, alopecia, hypokalemia, interstitial lung disease/pneumonitis and an increase in aldosterone; 34.8% of participants experienced interstitial lung disease/pneumonitis, but only 2 had a severity of grade 3. At 1.5 mg/kg every 3 weeks, the recommended phase II dose, the objective response rate was 65.5%, the disease control rate was 100%, and the median progression-free survival was 17 months. «These results showed that ARX788 had a manageable safety profile, circulating stability, and promising preliminary signs of clinical activity in HER2-positive metastatic breast cancer patients who progressed on prior anti-HER2 therapies. The non-cleavable linker rendered the antibody-drug conjugate highly stable in the circulation, resulting in relatively less payload-related off-target toxicity. A pivotal phase II/III randomized controlled, multicenter clinical trial is rapidly enrolling HER2-positive metastatic breast cancer patients to confirm these findings», authors conclude.