A Phase 1 Study of a CDH6-Targeting Antibody-Drug Conjugate in Patients with Advanced Solid Tumors with Evaluation of Inflammatory and Neurological Adverse Events
Patrick Schoffski, Nicole Concin, Cristina Suarez, Vivek Subbiah, Yuichi Ando, Shiling Ruan, Joel P Wagner, Keith Mansfield, Xu Zhu, Shizuka Origuchi, Sarah DiDominick, Carl U Bialucha, Jason E Faris, Ben Tran
ONCOLOGY RESEARCH AND TREATMENT | KARGER | Published : 2021
PURPOSE: This first-in-human study (NCT02947152) evaluated the safety, tolerability, pharmacokinetics, and preliminary efficacy of HKT288, a first-in-class CDH6-targeting antibody-drug conjugate (ADC). EXPERIMENTAL DESIGN: HKT288 was administered intravenously (IV) every 3 weeks until patients experienced unacceptable toxicity or progressive disease (PD). The starting dose of 0.3 mg/kg was determined based on the highest nonseverely toxic dose in monkeys, which was 2 mg/kg IV weekly. Based on preclinical toxicology, skin, eyes, bone marrow, and liver were expected targets of toxicity. RESULTS: Nine patients were enrolled: 5 with renal cell carcinoma and 4 with epithelial ovarian cancer. The ..View full abstract
The authors received financial support from Novartis Oncology.