Preliminary Results of Safety and PK of Telisotuzumab Vedotin (T) in Japanese Patients with Advanced Solid Tumors

Abstract

Abstract Background c-Met is a receptor tyrosine kinase overexpressed in 30-50% of solid tumors. c-Met protein overexpression have been associated with poor clinical outcomes in many cancers. T (teliso-v, ABBV-399) is a first-in-class c-Met specific antibody drug conjugate that is cytotoxic to cancer cells with overexpressed c Met and demonstrates antitumor activity in human tumor xenografts. This Ph 1 study evaluates safety, PK and preliminary efficacy of T in Japanese patients (pts) with advanced solid tumors. Methods In this non-randomized, dose-escalation Ph 1 study (NCT03311477) in Japanese pts, 3 pts were treated with 2.4 mg/kg every 3 weeks (Q3W) and 6 pts with 2.7 mg/kg Q3W. Serial blood samples were collected in Cycle 1 and 3 for PK assessments. IHC of c-Met status was retrospectively evaluated. Results As of Nov 2018, 9 pts were enrolled. 8 pts experienced adverse events (AEs). The most frequent treatment-emergent AEs (any grade) were neuropathy (44%), decreased appetite (33%) and nausea (33%). 5 pts (56%) had dose interruption due to an AE. Grade 3/4 AEs including decreased neutrophil count in 2 pts (22%). There were no dose limiting toxicities and 2.7 mg/kg Q3W was tolerable. 2 pts (ovarian and urothelial carcinoma) had confirmed partial responses, both of which are ongoing. c-Met expression levels from archived specimens from these 2 pts were not high (H-Score:35 and 10, respectively). Median progression free survival was 7 (95% CI; 1, not calculated) months. The maximum observed serum concentration (Cmax) of T was 55.5-63.0 µg/mL (%CV: 22-26%) and the area under the serum concentration-time curve (AUCinf) of T was 4400-5200 µg*h/mL (%CV: 19-23%) across the 2 doses in Japanese pts. The half-life for T and the free MMAE payload was determined to be 3-4 days and 4-6 days respectively. Conclusions Preliminary safety, PK and efficacy in Japanese pts with solid tumors suggest T was tolerated and showed encouraging anti-cancer effects, warranting continued study.