TAK-264 (MLN0264) in Previously Treated Asian Patients with Advanced Gastrointestinal Carcinoma Expressing Guanylyl Cyclase C: Results from an Open-Label, Non-randomized Phase 1 Study.
- Author:
Yung Jue BANG
1
;
Toshimi TAKANO
;
Chia Chi LIN
;
Adedigbo FASANMADE
;
Huyuan YANG
;
Hadi DANAEE
;
Takayuki ASATO
;
Thea KALEBIC
;
Hui WANG
;
Toshihiko DOI
Author Information
- Publication Type:Clinical Trial ; Original Article
- Keywords: Clinical trial; Gastrointestinal cancer; Stomach
- MeSH: Adenocarcinoma; Adrenal Insufficiency; Adult; Anorexia; Ascites; Asian Continental Ancestry Group*; Asthenia; Disease Progression; Esophagogastric Junction; Gastrointestinal Neoplasms; Guanylate Cyclase*; Half-Life; Hemorrhage; Humans; Hypertension; Infusions, Intravenous; Maximum Tolerated Dose; Nausea; Neutropenia; Pharmacokinetics; Stomach
- From:Cancer Research and Treatment 2018;50(2):398-404
- CountryRepublic of Korea
- Language:English
- Abstract: PURPOSE: This phase 1 dose-escalation portion of the study evaluated the safety, pharmacokinetics (PK), and antitumor activity of TAK-264 in Asian patients with advanced gastrointestinal (GI) carcinoma or metastatic or recurrent gastric or gastroesophageal junction adenocarcinoma expressing guanylyl cyclase C (GCC). MATERIALS AND METHODS: Adult patients with advanced GI malignancies expressing GCC (H-score ≥ 10) received TAK-264 on day 1 of 3-week cycles as 30-minute intravenous infusions for up to 1 year or until disease progression or unacceptable toxicity. The primary objectives were to evaluate the safety profile including dose-limiting toxicities (DLTs) during cycle 1, determine the maximum tolerated dose (MTD), and characterize the PK profile of TAK-264. RESULTS: Twelve patients were enrolled and treated with 1.2 mg/kg (n=3), 1.5 mg/kg (n=3), or 1.8 mg/kg TAK-264 (n=6). Median number of treatment cycles received was two (range, 1 to 10). None of the patients experienced a DLT and the MTD was not determined. Ten patients (83%) experienced adverse events (AEs). The most common were neutropenia, anorexia, and nausea (each reported by four patients). Five patients (42%) experienced grade ≥ 3 AEs consisting of tumor hemorrhage and hypertension, ascites, adrenal insufficiency, neutropenia and asthenia. Serum exposure to TAK-264 increased proportionally with the dose and the median half-life was approximately 5.5-6.6 days. No patients experienced an objective response. CONCLUSION: TAK-264 demonstrated a manageable safety profile with limited antitumor activity consistent with studies conducted in Western patients with advanced GI malignancies. TAK-264 exposure increased proportionally with the dose.
