Cancer Res Treat.  2018 Apr;50(2):398-404. 10.4143/crt.2017.074.

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

Affiliations
  • 1Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea. bangyj@snu.ac.kr
  • 2Department of Medical Oncology, Toranomon Hospital, Tokyo, Japan.
  • 3Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan.
  • 4Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, Cambridge, MA, USA.
  • 5Department of Experimental Therapeutics, National Cancer Center Hospital East, Chiba, Japan.

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.

Keyword

Clinical trial; Gastrointestinal cancer; Stomach

MeSH Terms

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
Guanylate Cyclase

Reference

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