Phase I Study of A166, a Novel Antibody-Drug Conjugate in Advanced HER2-expressing Solid Tumors

Abstract Purpose: In this phase I study, the safety, pharmacokinetics, and antitumor activity of a novel HER2 targeted antibody–drug conjugate A166 were evaluated in patients with HER2-expressing advanced solid tumors. Experimental Design: Patients received A166 at doses of 0.1, 0.3, 0.6, 1.2, 2.4, 3.6, 4.8, or 6.0 mg/kg Q3W. Results: In total, 81 patients who had progressed on standard treatment were enrolled. No dose-limiting toxicity was observed. The most common treatment-related adverse events at grade 3 or higher were corneal epitheliopathy (30.9%), blurred vision (18.5%), dry eyes (7.4%), and peripheral sensory neuropathy (6.2%). The Cmax and area under curve of Duo-5, its free payload, were about 0.1% and 0.2% of those of the ADC, respectively. For all assessable HER2-positive breast cancer patients enrolled in 4.8 mg/kg and 6.0 mg/kg cohorts, corresponding ORR was 73.9% (17/23) and 68.6% (24/35), respectively; and median PFS was 12.3 and 9.4 months, respectively. Conclusions: A166 had a recommended phase II dose of 4.8 mg/kg, manageable toxicity, good stability in the circulation and promising antitumor activities in HER2-positive breast cancer patients. Trial registration: CTR20181301 (www.chinadrugtrials.org.cn)