Cancer Research and Treatment

Original Articles

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: Yung-Jue Bang, Toshimi Takano, Chia-Chi Lin, Adedigbo Fasanmade, Huyuan Yang, Hadi Danaee, Takayuki Asato, Thea Kalebic, Hui Wang, Toshihiko Doi; Cancer Res Treat. 2018;50(2):398-404. Published online May 10, 2017; DOI: https://doi.org/10.4143/crt.2017.074

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.

Citations

Citations to this article as recorded by

Antibody–drug conjugates in gastric cancer: from molecular landscape to clinical strategies
Jia-Lin Hao, Xin-Yun Li, Yu-Tong Liu, Ji-Xuan Lang, Di-Jie Liu, Chun-Dong Zhang
Gastric Cancer.2024; 27(5): 887. CrossRef
Asia‐Inclusive Clinical Research and Development Enabled by Translational Science and Quantitative Clinical Pharmacology: Toward a Culture That Challenges the Status Quo
Karthik Venkatakrishnan, Neeraj Gupta, Patrick F. Smith, Tiffany Lin, Neil Lineberry, Tatiana Ishida, Lin Wang, Mark Rogge
Clinical Pharmacology & Therapeutics.2023; 113(2): 298. CrossRef
A phase I, first-in-human study of TAK-164, an antibody–drug conjugate, in patients with advanced gastrointestinal cancers expressing guanylyl cyclase C
Richard Kim, Alexis D. Leal, Aparna Parikh, David P. Ryan, Shining Wang, Brittany Bahamon, Neeraj Gupta, Aaron Moss, Joanna Pye, Harry Miao, Haig Inguilizian, James M. Cleary
Cancer Chemotherapy and Pharmacology.2023; 91(4): 291. CrossRef
Guanylate cyclase-C Signaling Axis as a theragnostic target in colorectal cancer: a systematic review of literature
Moein Piroozkhah, Ali Aghajani, Pooya Jalali, Arvin Shahmoradi, Mobin Piroozkhah, Younes Tadlili, Zahra Salehi
Frontiers in Oncology.2023;[Epub] CrossRef
Antibody-drug conjugates: Resurgent anticancer agents with multi-targeted therapeutic potential
Claudia Ceci, Pedro Miguel Lacal, Grazia Graziani
Pharmacology & Therapeutics.2022; 236: 108106. CrossRef
Research Progress of Antibody–Drug Conjugate Therapy for Advanced Gastric Cancer
Na Wang, Qingyun Mei, Ziwei Wang, Lu Zhao, Dou Zhang, Dongying Liao, Jinhui Zuo, Hongxia Xie, Yingjie Jia, Fanming Kong
Frontiers in Oncology.2022;[Epub] CrossRef
Antibody drug conjugates in gastrointestinal cancer: From lab to clinical development
Davinder Singh, Divya Dheer, Abhilash Samykutty, Ravi Shankar
Journal of Controlled Release.2021; 340: 1. CrossRef

9,382 View
211 Download
8 Web of Science
7 Crossref

Phase I Study of Axitinib in Combination with Cisplatin and Capecitabine in Patients with Previously Untreated Advanced Gastric Cancer: Do-Youn Oh, Toshihiko Doi, Kuniaki Shirao, Keun-Wook Lee, Sook Ryun Park, Ying Chen, Liqiang Yang, Olga Valota, Yung-Jue Bang; Cancer Res Treat. 2015;47(4):687-696. Published online February 12, 2015; DOI: https://doi.org/10.4143/crt.2014.225

Abstract PDF PubReader ePub

Purpose
This phase I trial evaluated the question of whether the standard starting dose of axitinib could be administered in combination with therapeutic doses of cisplatin/capecitabine in patients with previously untreated advanced gastric cancer, and assessed overall safety, pharmacokinetics, and preliminary antitumor activity of this combination.
Materials and Methods
Patients in dose level (DL) 1 received axitinib 5 mg twice a day (days 1 to 21) with cisplatin 80 mg/m2 (day 1) and capecitabine 1,000 mg/m2 twice a day (days 1 to 14) in 21-day cycles. Maximum tolerated dose (MTD) was the highest dose at which ≤ 30% of the first 12 patients experienced a dose-limiting toxicity (DLT) during cycle 1. Ten additional patients were enrolled and treated at the MTD in order to obtain additional safety and pharmacokinetic data.
Results
Three DLTs occurred during cycle 1 in three (25%) of the first 12 patients: ruptured abdominal aortic aneurysm, acute renal failure, and > 5 consecutive days of missed axitinib due to thrombocytopenia. DL1 was established as the MTD, since higher DL cohorts were not planned. Common grade 3/4 non-hematologic adverse events in 22 patients treated at DL1 included hypertension (36.4%) and decreased appetite and stomatitis (18.2% each). Cisplatin/capecitabine slightly increased axitinib exposure; axitinib decreased capecitabine and 5-fluorouracil exposure. Eight patients (36.4%) each had partial response or stable disease. Median response duration was 9.1 months; median progression-free survival was 3.8 months.
Conclusion
In patients with advanced gastric cancer, standard doses of axitinib plus therapeutic doses of cisplatin and capecitabine could be administered in combination. Adverse events were manageable.

Citations

Citations to this article as recorded by

Construction of a hypoxia-immune-related prognostic panel based on integrated single-cell and bulk RNA sequencing analyses in gastric cancer
Cuncan Deng, Guofei Deng, Hongwu Chu, Songyao Chen, Xiancong Chen, Xing Li, Yulong He, Chunhui Sun, Changhua Zhang
Frontiers in Immunology.2023;[Epub] CrossRef
Early TP53 Alterations Shape Gastric and Esophageal Cancer Development
Pranshu Sahgal, Brandon M. Huffman, Deepa T. Patil, Walid K. Chatila, Rona Yaeger, James M. Cleary, Nilay S. Sethi
Cancers.2021; 13(23): 5915. CrossRef
High ELK3 Expression is Associated with the VEGF-C/VEGFR-3 Axis and Gastric Tumorigenesis and Enhances Infiltration of M2 Macrophages
Wang Dazhi, Jiao Zheng, Ren Chunling
Future Medicinal Chemistry.2020; 12(24): 2209. CrossRef
RETRACTED: Long non-coding RNA LINC00978 promotes cell proliferation and tumorigenesis via regulating microRNA-497/NTRK3 axis in gastric cancer
Ju-Yuan Bu, Wei-Ze Lv, Yi-Feng Liao, Xiao-Yu Xiao, Bao-Jun Lv
International Journal of Biological Macromolecules.2019; 123: 1106. CrossRef
RETRACTED ARTICLE: Anti-gastric cancer effect of Salidroside through elevating miR-99a expression
Lin Yang, Yanan Yu, Qi Zhang, Xiaoyu Li, Cuiping Zhang, Tao Mao, Siliang Liu, Zibin Tian
Artificial Cells, Nanomedicine, and Biotechnology.2019; 47(1): 3500. CrossRef
Stomatitis and VEGFR-Tyrosine Kinase Inhibitors (VR-TKIs): A Review of Current Literature in 4369 Patients
Claudia Arena, Giuseppe Troiano, Alfredo De Lillo, Nunzio F. Testa, Lorenzo Lo Muzio
BioMed Research International.2018; 2018: 1. CrossRef
Anti-angiogenic Therapy in Patients with Advanced Gastric and Gastroesophageal Junction Cancer: A Systematic Review
Li-Tzong Chen, Do-Youn Oh, Min-Hee Ryu, Kun-Huei Yeh, Winnie Yeo, Roberto Carlesi, Rebecca Cheng, Jongseok Kim, Mauro Orlando, Yoon-Koo Kang
Cancer Research and Treatment.2017; 49(4): 851. CrossRef
Angiogenesis inhibitors in early development for gastric cancer
Mauricio P. Pinto, Gareth I. Owen, Ignacio Retamal, Marcelo Garrido
Expert Opinion on Investigational Drugs.2017; 26(9): 1007. CrossRef
HER2-induced metastasis is mediated by AKT/JNK/EMT signaling pathway in gastric cancer
Yiseul Choi, Young San Ko, Jin Ju Park, Youngsun Choi, Younghoon Kim, Jung-Soo Pyo, Bo Gun Jang, Douk Ho Hwang, Woo Ho Kim, Byung Lan Lee
World Journal of Gastroenterology.2016; 22(41): 9141. CrossRef

15,075 View
108 Download
11 Web of Science
9 Crossref

First
Prev
Page of 1
Next
Last

Search