DRUG TARGETS: MET A phase I study of an anti-MET antibody (telisotuzumab) in advanced cancers reported partial responses in MET amplified tumours
DRUG TARGETS, MET:
A phase I study of an anti-MET antibody (telisotuzumab) in advanced cancers reported partial responses in MET amplified tumours (4/10 subjects with MET/CEP7 ratio ≥2 in ≥20% of cells) but no response where MET copy number was normal.
Phase I Dose-Escalation and -Expansion Study of Telisotuzumab (ABT-700), an Anti–c-Met Antibody, in Patients with Advanced Solid Tumors
J.H. Strickler at al Mol Can Thera DOI: 10.1158/1535-7163.MCT-19-0529 Published May 2020
This first-in-human phase I study evaluated the pharmacokinetics, safety, and preliminary efficacy of telisotuzumab, formerly called ABT-700, an antagonistic antibody directed against c-Met.
For dose escalation (3+3 design), 3 to 6 patients with advanced solid tumors were enrolled into four dose cohorts (5–25 mg/kg). In the dose-expansion phase, a subset of patients was prospectively selected for MET amplification (FISH screening). Patients received telisotuzumab intravenously on day 1 every 21 days.
For dose expansion, 15 mg/kg was chosen as the dose on the basis of safety, pharmacokinetics, and other data from the escalation cohorts. Forty-five patients were enrolled and received at least one dose of telisotuzumab (dose escalation, n = 15; dose expansion, n = 30). Telisotuzumab showed a linear pharmacokinetics profile; peak plasma concentration was proportional to dose level. There were no acute infusion reactions and no dose-limiting toxicities were observed.
The most common treatment-related adverse events included hypoalbuminemia (n = 9, 20.0%) and fatigue (n = 5, 11.1%). By Response Evaluation Criteria In Solid Tumors (RECIST), 4 of 10 (40.0%) patients with MET-amplified tumors had confirmed partial response in target lesions (one ovarian, two gastric, and one esophageal), two (20.0%) had stable disease, three (30.0%) had progressive disease; one patient was unable to be evaluated. Among patients with nonamplified tumors (n = 35), no objective responses were observed; however, 11 patients had stable disease per RECIST criteria.
In conclusion, telisotuzumab has an acceptable safety profile with clinical activity observed in patients with MET-amplified advanced solid tumors.