Publications by authors named "T Kalebic"
Article Synopsis
- Antibody-drug conjugates (ADCs) like TAK-264, which targets guanylyl cyclase C (GCC), show promise in treating pancreatic cancer through a targeted approach.
- The study assessed TAK-264's efficacy in eleven pancreatic cancer cell lines and ten patient-derived xenograft models, revealing significant tumor growth inhibition in most models treated with the ADC.
- Increased GCC expression was found in tumor tissues, and the study suggests further research into ADCs targeting GCC is warranted based on the encouraging anti-tumor effects of TAK-264.
Background: The transmembrane receptor guanylate cyclase-C (GCC) has been found to be expressed in colorectal cancers. However, limited data are available on GCC protein expression in non-colorectal gastrointestinal tumors and few studies have reported whether GCC protein expression was consistently preserved in synchronous primary and metastatic cancer tissues.
Methods: GCC protein status was assessed by immunohistochemistry in tumor specimens from individuals (n = 627) with gastrointestinal tumors, including esophageal (n = 130), gastric (n = 276), pancreatic (n = 136), and colorectal (n = 85) primary and metastatic tumors.
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.
Invest New Drugs
October 2017
Article Synopsis
- This study assessed TAK-264's effectiveness and safety in patients with advanced pancreatic adenocarcinoma expressing guanylyl cyclase C (GCC) after previous treatments.
- A total of 43 patients were treated with TAK-264, showing a low overall response rate of 3%, with only one patient achieving a partial response.
- While the drug had a manageable safety profile, many patients experienced adverse events, with gastrointestinal issues being the most common, leading to the conclusion that TAK-264 is not a viable option for further clinical trials.
Article Synopsis
- This study focused on the safety and efficacy of TAK-264 in Asian patients with advanced GI cancers expressing GCC.
- Twelve patients received various doses of TAK-264 over a period of up to one year, with no dose-limiting toxicities identified and a median of two treatment cycles completed.
- While the drug had a manageable safety profile, with some common adverse effects, it showed limited antitumor activity and no objective responses were observed.
Phase II study of the antibody-drug conjugate TAK-264 (MLN0264) in patients with metastatic or recurrent adenocarcinoma of the stomach or gastroesophageal junction expressing guanylyl cyclase C.
Invest New Drugs
April 2017
Background The first-in-class antibody-drug conjugate TAK-264 (formerly MLN0264) consists of an antibody targeting guanylyl cyclase C (GCC) conjugated to monomethyl auristatin E (MMAE) via a peptide linker. This phase II study evaluated the efficacy and safety of TAK-264 in patients with adenocarcinoma of the stomach or gastroesophageal junction expressing GCC, who had progressed on ≥1 line of prior therapy. Methods This study used a two-stage design, with an interim analysis conducted after stage I to determine whether to continue to stage II or discontinue on the grounds of futility.
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