First-in-Human Phase I Study of Aprutumab Ixadotin, a Fibroblast Growth Factor Receptor 2 Antibody-Drug Conjugate (BAY 1187982) in Patients with Advanced Cancer

  • Target Oncol. 2019 Oct;14(5):591-601. doi: 10.1007/s11523-019-00670-4.
Sung-Bae Kim  1 ,  Funda Meric-Bernstam  2 ,  Aparna Kalyan  3 ,  Aleksei Babich  4 ,  Rong Liu  5 ,  Takahiko Tanigawa  6 ,  Anette Sommer  4 ,  Motonobu Osada  4 ,  Frank Reetz  7 ,  Dirk Laurent  4 ,  Sabine Wittemer-Rump  4 ,  Jordan Berlin  8
Affiliations
  • 1. Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea. [email protected].
  • 2. The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • 3. Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
  • 4. Bayer AG, Berlin, Germany.
  • 5. Bayer Healthcare, Whippany, NJ, USA.
  • 6. Bayer Yakuhin, Ltd., Osaka, Japan.
  • 7. Bayer AG, Basel, Switzerland.
  • 8. Vanderbilt University Medical Center, Nashville, TN, USA.
PMID: 31502117 DOI: 10.1007/s11523-019-00670-4
Abstract

Background: Fibroblast Growth Factor receptor (FGFR) 2 is overexpressed in several tumor types, including triple-negative breast Cancer and gastric Cancer, both of which have a high unmet medical need. Aprutumab ixadotin (BAY 1187982) is the first antibody-drug conjugate (ADC) to target FGFR2 and the first to use a novel auristatin-based payload.

Objective: This first-in-human trial was conducted to determine the safety, tolerability, and maximum tolerated dose (MTD) of aprutumab ixadotin in patients with advanced solid tumors from Cancer indications known to be FGFR2-positive.

Patients and methods: In this open-label, multicenter, phase I dose-escalation trial (NCT02368951), patients with advanced solid tumors received escalating doses of aprutumab ixadotin (starting at 0.1 mg/kg body weight), administered intravenously on day 1 of every 21-day cycle. Primary endpoints included safety, tolerability, and the MTD of aprutumab ixadotin; secondary endpoints were pharmacokinetic evaluation and tumor response to aprutumab ixadotin.

Results: Twenty patients received aprutumab ixadotin across five cohorts, at doses of 0.1-1.3 mg/kg. The most common grade ≥ 3 drug-related adverse events were anemia, aspartate aminotransferase increase, proteinuria, and thrombocytopenia. Dose-limiting toxicities were thrombocytopenia, proteinuria, and corneal epithelial microcysts, and were only seen in the two highest dosing cohorts. The MTD was determined to be 0.2 mg/kg due to lack of quantitative data following discontinuations at 0.4 and 0.8 mg/kg doses. One patient had stable disease; no responses were reported.

Conclusions: Aprutumab ixadotin was poorly tolerated, with an MTD found to be below the therapeutic threshold estimated preclinically; therefore, the trial was terminated early. CLINICALTRIALS.

Gov identifier: NCT02368951.

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