Xermelo (telotristat etiprate)

P3, N=79, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Oct 2025 --> Aug 2026

P2, N=23, Completed, Emory University | Active, not recruiting --> Completed

Therapeutic options include somatostatin analogs, multi-targeted tyrosine kinase inhibitors (e.g., sunitinib), or mammalian targets of rapamycin (mTOR) inhibitors (e.g., everolimus), telotristat ethyl, chemotherapy, and peptide-receptor radionuclide therapy. Biomarkers may assist in both the diagnosis and post-treatment follow-up in patients with GEP-NETs. The next decade of research on GEP-NETs is promising and should provide new insights into the molecular underpinnings of this disease, therapy selection, and the sequencing of the available therapies, along with the potential role of AL in NET pharmacotherapy.

Telotristat ethyl affects the expression of genes associated with the ECM and interferes with SI-NET-fibroblast crosstalk. Further analysis is required; however, this study represents an important step in understanding the mechanisms of telotristat ethyl when treating SI-NET patients.

P2, N=4, Completed, Barbara Ann Karmanos Cancer Institute | Recruiting --> Completed

P3, N=79, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Aug 2024 --> Aug 2025 | Trial primary completion date: Aug 2024 --> Aug 2025

P3, N=79, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting | N=60 --> 79

P=N/A, N=223, Completed, TerSera Therapeutics LLC | N=349 --> 223

P3, N=60, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Jul 2027 --> Aug 2024 | Trial primary completion date: Jul 2027 --> Aug 2024

In preclinical models of cholangiocarcinoma (CCA) telotristat ethyl (TE), a tryptophan hydroxylase inhibitor that reduces production of serotonin, enhanced the antiproliferative effects of gemcitabine and cisplatin (GC) chemotherapy. The study did not achieve its primary endpoint of 60% of patients on TE plus GC chemotherapy being alive and progression free at 6 months. TE did reduce 5-HIAA levels in a subset of pts; however, this did not correlate to improved clinical outcomes. No significant safety issues noted with TE in combination with GC chemotherapy.

The most widely used are somatostatin analogues with three clinically approved drugs: lanreotide and octreotide (first-generation) and pasireotide (second-generation). Both everolimus and interferon used in combination with octreotide have shown significant reduction in urinary 5-hydroxyindoleacetic acid compared to octreotide alone. Telotristat ethyl has been increasingly utilised for patients with symptoms despite taking somatostatin analogues...There are therefore numerous different therapies. This paper describes the pathophysiology and therapy of carcinoid syndrome.

Systemic approaches to control tumor growth and hormonal secretion include somatostatin analogs (SSAs), followed by options including peptide receptor radiotherapy (PRRT), everolimus and liver embolization. Diuretics are the mainstay of heart failure symptom management for patients who develop CaHD. Considerations for future research are discussed, including the ongoing TELEHEART (TELotristat Ethyl in a HEART biomarker study) trial involving telotristat and not yet activated CHARRT (Carcinoid Heart disease And peptide Receptor Radiotargetted Therapy) study involving PRRT with lutetium 177 (177Lu) dotatate.