Phase I Dose-Escalation and -Expansion Study of Telisotuzumab (ABT-700), an Anti-c-Met Antibody, in Patients with Advanced Solid Tumors

John H. Strickler, Patricia LoRusso, Ravi Salgia, Yoon Koo Kang, Chia Jui Yen, Chia Chi Lin, Peter Ansell, Monica Motwani, Shekman Wong, Huibin Yue, Lan Wang, Edward Reilly, Daniel Afar, Louie Naumovski, Ramesh K. Ramanathan

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1210-1217
Number of pages8
JournalMolecular cancer therapeutics
Volume19
Issue number5
DOIs
Publication statusPublished - 2020 May 1

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Phase I Dose-Escalation and -Expansion Study of Telisotuzumab (ABT-700), an Anti-c-Met Antibody, in Patients with Advanced Solid Tumors'. Together they form a unique fingerprint.

  • Cite this

    Strickler, J. H., LoRusso, P., Salgia, R., Kang, Y. K., Yen, C. J., Lin, C. C., Ansell, P., Motwani, M., Wong, S., Yue, H., Wang, L., Reilly, E., Afar, D., Naumovski, L., & Ramanathan, R. K. (2020). Phase I Dose-Escalation and -Expansion Study of Telisotuzumab (ABT-700), an Anti-c-Met Antibody, in Patients with Advanced Solid Tumors. Molecular cancer therapeutics, 19(5), 1210-1217. https://doi.org/10.1158/1535-7163.MCT-19-0529