371P - First-in-human phase 1, dose-escalation and -expansion study of ABBV-399, an antibody-drug conjugate (ADC) targeting c-Met, in patients (pts) with...
| Date | 10 October 2016 |
| Event | ESMO 2016 Congress |
| Session | Poster display |
| Topics | Drug Development |
| Presenter | Eric Angevin |
| Citation | Annals of Oncology (2016) 27 (6): 114-135. 10.1093/annonc/mdw368 |
| Authors |
E. Angevin1, K. Kelly2, R. Heist3, D. Morgensztern4, C. Weekes5, T.M. Bauer6, R.K. Ramanathan7, J. Nemunaitis8, X. Fan9, O. Olyaie9, A. Parikh9, E. Reilly10, D. Afar9, L. Naumovski9, J. Strickler11
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Abstract
Background
The c-Met receptor is overexpressed in multiple tumors. ABBV-399 is a first-in-class ADC composed of ABT-700, a previously described anti–c-Met antibody, conjugated to monomethyl auristatin E (a microtubule inhibitor). Preclinical data support ADC ABBV-399 as a unique strategy to deliver a potent cytotoxin directly to c-Met+ tumor cells (∼30-50% of tumors overexpress c-Met).
Methods
In a 3 + 3 dose-escalation design, ABBV-399 was administered at doses ranging from 0.15 to 3.3 mg/kg once every 21 days to pts with metastatic solid tumors (NCT02099058). ABBV-399 was then studied in a dose-expansion cohort in pts with c-Met+ (immunohistochemistry [IHC] H-score ≥150) non-small cell lung cancer (NSCLC). Overexpression of c-Met was assessed by an IHC assay utilizing the SP44 antibody (Ventana; Tucson, AZ, USA).
Results
As of March 31, 2016, 48 pts received at least 1 dose of ABBV-399. Approximately dose-proportional increases of area under the curve for ABBV-399 and total antibody were observed after single-dose administration. Half-lives for ABBV-399 and total antibody were approximately 2 to 4 days. Dose-limiting toxicity of febrile neutropenia occurred in 1 pt at 3 mg/kg and 1 pt (with septic shock) at 3.3 mg/kg. A dose of 2.7 mg/kg was chosen for dose expansion based primarily on safety and tolerability. There were no treatment-related deaths. Treatment-related adverse events occurring in ≥10% of pts (including all dose levels and all grades) were fatigue (22.9%), nausea (20.8%), neuropathy (14.6%), decreased appetite (12.5%), vomiting (12.5%), and hypoalbuminemia (10.4%). Three of 16 (18.8%) ABBV-399–treated c-Met+ NSCLC pts had a partial response with duration of response 1 + , 3, and 4.5 mo. At week 12, 6 of 16 (37.5%) had disease control. There were no responses among pts with c-Met–negative tumors.
Conclusions
ABBV-399 is well tolerated at a dose of 2.7 mg/kg every 21 days and has demonstrated promising antitumor activity in pts with cMet+ NSCLC. Assessment of antitumor activity and safety of ABBV-399 in c-Met+ pts will continue as monotherapy and in combination with standard of care.
Clinical trial identification
NCT02099058
Legal entity responsible for the study
AbbVie, Inc.
Funding
AbbVie, Inc.
Disclosure
D. Morgensztern: Speaker: Genentech, Boehringer Ingelheim; consultant: Genentech, Celgene, Heat Biologics, Bristol-Myers Squibb. R.K. Ramanathan, J. Strickler: Research funding from AbbVie. X. Fan, O. Olyaie, A. Parikh, E. Reilly, D. Afar, L. Naumovski: Employed by AbbVie and may own stock. All other authors have declared no conflicts of interest.