Phase 1, Open-Label, Dose-Escalation and Expansion Study of ABBV-399, an Antibody Drug Conjugate (ADC) Targeting C-Met, in Patients (pts) with Advanced Solid Tumors.

2510 Background: The c-Met receptor is overexpressed in multiple tumors. ABBV-399 is a first-in-class antibody-drug conjugate (ADC) comprised of the anti-c-Met antibody, ABT-700, and monomethyl auristatin E. Although prior efforts at targeting c-Met overexpression have met with limited clinical success, an ADC directed against c-Met represents a unique strategy to deliver a potent cytotoxin directly to c-Met+ tumor cells. 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). The recommended single-agent phase 2 dose (RPTD) of ABBV-399 was then studied in a dose-expansion cohort in pts with c-Met+ (immunohistochemistry (IHC) ≥2+) non-small cell lung cancer (NSCLC). c-Met overexpression was assessed by an IHC assay utilizing the SP44 antibody (Ventana). Results: As of January 4, 2016, 45 pts received at least 1 dose of ABBV-399. Dose-proportional increases of area under the curve (AUC) for ABBV-399 and total antibody were observed after single dose administration. Half-lives for ABBV-399 and total antibody were approximately 2-4 days. Dose-limiting toxicity (DLT) of febrile neutropenia occurred in 1 pt at 3 mg/kg and 1 pt (with septic shock) at 3.3 mg/kg. The RPTD of 2.7 mg/kg was chosen based primarily on safety and tolerability. There were no toxic deaths. Treatment-related adverse events occurring in ≥10% of pts (including all dose levels and all grades) were fatigue (20%), nausea (17.8%), neuropathy (13.3%), decreased appetite (13.3%), hypoalbuminemia (11.1%), and vomiting (11%). 3/10 evaluable c-Met+ NSCLC pts had a partial response; the duration of response ranged from 1+ to 5 months. There were no responses among 9 pts with c-Met negative tumors. Conclusions: ABBV-399 is well tolerated at the RPTD of 2.7 mg/kg and has demonstrated promising anti-tumor activity in pts with cMet+ NSCLC. The study will continue to assess the anti-tumor activity and safety of ABBV-399 in c-Met+ pts both as monotherapy and in combination with standard of care. Clinical trial information: NCT02099058.