Title |
A phase II study of antibody-drug conjugate, TAK-264 (MLN0264) in previously treated patients with advanced or metastatic pancreatic adenocarcinoma expressing guanylyl cyclase C
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Published in |
Investigational New Drugs, May 2017
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DOI | 10.1007/s10637-017-0473-9 |
Pubmed ID | |
Authors |
Khaldoun Almhanna, David Wright, Teresa Macarulla Mercade, Jean-Luc Van Laethem, Antonio Cubillo Gracian, Carmen Guillen-Ponce, Jason Faris, Carolina Muriel Lopez, Richard A. Hubner, Johanna Bendell, Alain Bols, Jaime Feliu, Naureen Starling, Peter Enzinger, Devalingham Mahalingham, Wells Messersmith, Huyuan Yang, Adedigbo Fasanmade, Hadi Danaee, Thea Kalebic |
Abstract |
Background This phase II open-label, multicenter study evaluated the efficacy, safety, and tolerability of TAK-264 in previously treated patients with advanced or metastatic pancreatic adenocarcinoma expressing guanylyl cyclase C (GCC). Methods Patients with advanced or metastatic pancreatic adenocarcinoma expressing GCC (H-score ≥ 10) received TAK-264 1.8 mg/kg on day 1 of a 21-day cycle as a 30-min intravenous infusion for up to 1 year or until disease progression or unacceptable toxicity. The primary objective was overall response rate (ORR [complete response + partial response (PR)]). Secondary objectives included evaluations of the safety and pharmacokinetic profile of TAK-264 (NCT02202785). Results 43 patients were enrolled and treated with 1.8 mg/kg TAK-264: 11, 15, and 17 patients with low, intermediate, and high GCC expression, respectively. Median number of treatment cycles received was two (range 1-10). The ORR was 3%, including one patient with intermediate GCC expression who achieved a PR. All patients experienced ≥1 adverse events (AE). The majority of patients experienced grade 1/2 AEs affecting the gastrointestinal tract. Fifteen (35%) patients experienced ≥grade 3 drug-related AEs; five (12%) patients had a serious AE. The most common (≥10% of patients) all-grade drug-related AEs were nausea (33%), fatigue (28%), neutropenia (23%), decreased appetite (23%), vomiting (16%), asthenia (16%), and alopecia (14%). Conclusions TAK-264 demonstrated a manageable safety profile; however, the low efficacy of TAK-264 observed in this study did not support further clinical investigation. |
X Demographics
Geographical breakdown
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Spain | 1 | 33% |
Unknown | 2 | 67% |
Demographic breakdown
Type | Count | As % |
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Scientists | 2 | 67% |
Practitioners (doctors, other healthcare professionals) | 1 | 33% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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Unknown | 55 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Ph. D. Student | 11 | 20% |
Student > Bachelor | 6 | 11% |
Other | 6 | 11% |
Researcher | 5 | 9% |
Student > Doctoral Student | 3 | 5% |
Other | 9 | 16% |
Unknown | 15 | 27% |
Readers by discipline | Count | As % |
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Biochemistry, Genetics and Molecular Biology | 10 | 18% |
Medicine and Dentistry | 9 | 16% |
Agricultural and Biological Sciences | 5 | 9% |
Nursing and Health Professions | 4 | 7% |
Pharmacology, Toxicology and Pharmaceutical Science | 4 | 7% |
Other | 7 | 13% |
Unknown | 16 | 29% |