Abstract 1414TiP
Background
Acquired resistance to third-generation epidermal growth factor receptor (EGFR) inhibitors (eg, osimertinib) may result in MET gene amplification and/or c-MET protein overexpression. Telisotuzumab vedotin (ABBV-399; teliso-v), an anti–c-MET antibody-drug conjugate that can both disrupt c-MET signaling and deliver a cytotoxic payload into tumor cells, has shown antitumor activity in a phase 1/1b trial (NCT02099058) in patients (pts) with non-small cell lung cancer (NSCLC) with c-MET overexpression. Here we describe the teliso-v plus osimertinib cohort (arm E) of this trial.
Trial design
Arm E of this phase 1/1b open-label study evaluates safety, pharmacokinetics, and preliminary efficacy of teliso-v, administered intravenously once every 2 weeks, in combination with oral osimertinib (80 mg once a day) in pts with metastatic NSCLC whose disease progressed on osimertinib. Pts must have documented osimertinib-sensitive EGFR mutations, and c-MET overexpression (defined by central immunohistochemistry test) in tumor tissue obtained post-osimertinib progression. Arm E consists of safety lead-in (SLP; n=3–6), safety evaluation (SEP; n=3–12), and expansion (n=3–12) phases. Teliso-v will first be evaluated at 1.6 mg/kg and escalated to 1.9 mg/kg on the basis of safety signals in SLP and SEP phases. Radiographic tumor assessments will continue until disease progression, start of a new anticancer therapy, death, or consent withdrawal. Response evaluation will be based on Response Evaluation Criteria in Solid Tumors version 1.1. Planned enrollment is 3–24 pts; to date, 3 pts are enrolled.
Clinical trial identification
NCT02099058.
Editorial acknowledgement
Medical writing support was provided by Mary L. Smith, PhD, CMPP, from Aptitude Health, Atlanta, GA, and funded by AbbVie.
Legal entity responsible for the study
AbbVie.
Funding
AbbVie Inc.
Disclosure
D.R. Camidge: Advisory/Consultancy, Research grant/Funding (institution): AbbVie. J.W. Goldman: Research grant/Funding (institution): AbbVie; Honoraria (self), Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Genentech/Roche.
G.W. Cole, Z. Sun, C.J. Ocampo, P. Komarnitsky, V. Blot: Shareholder/Stockholder/Stock options, Full/Part-time employment: AbbVie.