374P - Phase I dose escalation (esc) trial of weekly intravenous (i.v.) BI 836845 in Japanese patients (pts) with advanced solid tumors

Date 10 October 2016
Event ESMO 2016 Congress
Session Poster display
Topics Clinical research
Basic Scientific Principles
Presenter Toshihiko Doi
Citation Annals of Oncology (2016) 27 (6): 114-135. 10.1093/annonc/mdw368
Authors T. Doi1, K. Shitara2, Y. Naito1, Y. Kuboki1, T. Kojima2, A. Hosono3, T. Yoshino2, H. Kawamoto4, Y. Tadayasu5, H. Ugai6, Y. Takeuchi7, T. Bogenrieder8, K. Yoh1
  • 1Department Of Experimental Therapeutics, National Cancer Center Hospital East, 277-8577 - Kashiwa/JP
  • 2Department Of Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa/JP
  • 3Rare Cancer Center, National Cancer Center Hospital East, Kashiwa/JP
  • 4Division Of Pediatric Oncology, National Cancer Center Hospital East, Kashiwa/JP
  • 5Clinical Pk/pd Group, Nippon Boehringer Ingelheim Co., Ltd., Kobe/JP
  • 6Biostatistics And Data Sciences Japan, Nippon Boehringer Ingelheim Co., Ltd, Tokyo/JP
  • 7Clinical Trial Management Department, Nippon Boehringer Ingelheim Co., Ltd, Tokyo/JP
  • 8Clinical Development And Medical Affairs, Boehringer Ingelheim Pharma GmbH & Co. KG, Vienna/AT

Abstract

Background

BI 836845 is an insulin-like growth factor (IGF) ligand-neutralizing humanized antibody that binds to IGF-1/IGF-2 ligands. This Phase I trial (NCT02145741) evaluated the maximum tolerated dose (MTD), safety, pharmacokinetics (PK), pharmacodynamics (PD), and activity of BI 836845.

Methods

Japanese pts with advanced tumors were recruited in a 3 + 3 dose esc design. BI 836845 was administered weekly i.v. (21-day cycles). Pts with IGF-driven tumors were recruited in an expansion (exp) cohort.

Results

In the esc part, 15 pts (60% male; median age 67 years, range 46–74; Eastern Cooperative Oncology Group performance status 0/1 in 67%/33% of pts) received BI 836845 across 3 doses: 750 mg (6); 1000 mg (3); and 1400 mg (6). Tumor types included esophageal (3), stomach (3), adrenal (2), colorectal (2), and non-small cell lung (2). No dose-limiting toxicities were observed; MTD was not reached. A relevant biological dose was selected at 1000 mg weekly i.v. based on previous safety, efficacy, and PK/PD data. In the exp part, 6 pts (median age 38 years, range 32–71) received BI 836845 at 1000 mg. Tumor types included sarcoma (2) and desmoid (2). In total, 11/21 pts (52%) had drug-related adverse events (AEs); those in ≥10% pts were fatigue (19%), neutropenia (19%), diarrhea (14%) and white blood cell count decreased (14%). No pt had a dose reduction or discontinued due to AEs. No relevant deviations from dose linearity of BI 836845 exposure were observed in the PK analysis (esc part). 5/15 pts (33%) in the esc part had stable disease (SD; mean duration 95 days). In the exp part, 1/6 pts (17%; desmoid tumor) had a partial response and 2/6 pts (33%) had SD (disease control rate 50%, mean duration 102 days).

Conclusions

These findings were similar to those of previous Phase I studies of weekly i.v. BI 836845 in Caucasian or other Asian patients.

Clinical trial identification

Clinical trial registration: NCT02145741

Legal entity responsible for the study

Boehringer Ingelheim

Funding

This study has received funding from Boehringer Ingelheim.

Disclosure

T. Doi: Membership on advisory board or board of directors (Boehringer Ingelheim); corporate sponsored research (Boehringer Ingelheim). T. Kojima: Research funding (Merk Serono). T. Yoshino: Corporate-sponsored research (GlaxoSmithKline, Boehringer Ingleheim GmbH). Y. Tadayasu, H. Ugai, Y. Takeuchi: Employment (Nippon Boehringer Ingelheim). T. Bogenrieder: Employment (Boehringer Ingelheim). All other authors have declared no conflicts of interest.