OBI-999 monotherapy was determined to be well-tolerated and safe for patients with advanced solid tumors; however, it was associated with dose-limiting non-cumulative neutropenia.
OBI-999 is a new antibody–drug conjugate comprising the Globo H-targeting antibody, OBI-999, combined with cytotoxic monomethyl auristatin E (MMAE). This study demonstrated that the drug was well-tolerated in patients with advanced solid tumors, in doses up to 1.2 mg/kg, which is the recommended dose for phase II of the study. The drug was administered once every three weeks and was associated with dose-limiting non-cumulative neutropenia. The study findings are published in JCO Precision Oncology.
OBI-999 Demonstrated Non-Linear Pharmacokinetics
This first-in-human sequential dose-escalation study demonstrated non-linear pharmacokinetics for OBI-999 in doses ranging from 0.4 to 1.6 mg/kg. The drug had lower clearance at comparatively higher doses. The levels of MMAE in the circulation were low compared to the antibody–drug conjugate; however, there was a disproportionate increase in the MMAE exposure in the 1.6 mg/kg drug cohort.
Treatment-Emergent Adverse Events in OBI-999 Administration
The most prevalent treatment-emergent adverse events observed throughout the study were anemia and neutropenia in patients with advanced solid tumors, with the majority of the TEAEs being moderate or mild in severity. OBI-999 was found to be safe and well-tolerated in study participants at a dose level of 1.2 mg/kg. However, patients treated at a 1.6 mg/kg dose level demonstrated grade 4 neutropenia.
OBI-999 monotherapy was found to be well-tolerated and safe for patients with advanced solid tumors at a once per three weeks dose of 1.2 mg/kg, without any significant adverse effects, except for dose-limiting non-cumulative neutropenia.
Tsimberidou, A. M., Vo, H. H., Beck, J., Shia, C. S., Hsu, P., & Pearce, T. E. (2023). First-in-Human Study of OBI-999, a Globo H-Targeting Antibody-Drug Conjugate, in Patients With Advanced Solid Tumors. JCO Precis Oncol, 7, e2200496. https://doi.org/10.1200/po.22.00496