Oral STAT3 Inhibitor, TTI-101, in Patients with Advanced Cancers

Active:	No
Cancer Type:	Breast Cancer Colon/Rectal Cancer Liver Cancer / Hepatoblastoma Lung Cancer Melanoma	NCT ID:	NCT03195699
Trial Phases:	Phase I	Protocol IDs:	SM_CP2016-0842 (primary) NCI-2022-01107
Eligibility:	18 - 65 Years, Male and Female	Study Type:	Treatment
Study Sponsor:	Tvardi Therapeutics, Incorporated
NCI Full Details:	http://clinicaltrials.gov/show/NCT03195699

Summary

Many patients have cancers that have increased activity of a protein called STAT3 that
contributes critically to the development and growth of their cancer. Despite our
knowledge of STAT3's importance to cancer, scientists and doctors have not developed a
drug that targets it and that patients can take to treat their cancer more effectively
than treatments that are now available. Tvardi Therapeutics, Incorporated has developed a
compound, TTI-101, which can be given by mouth and acts as a direct inhibitor of STAT3.
Administration of TTI-101 to mice demonstrated that it blocked growth of cancers of the
breast, head and neck, lung, and liver and it was safe when administered at high doses to
mice, rats, and dogs. In this application, Tvardi is proposing to further develop TTI-101
for treatment of solid tumors for which the prognosis is dismal. The investigators will
determine how safe it is when administered to patients with cancer, determine whether an
adequate dose can be administered to patients with cancer that will block STAT3 in their
cancer, and determine whether treatment with TTI-101 leads to reduced growth of their
cancer.

Objectives

Signal transducer and activator of transcription 3 (STAT3) is a member of a family of
seven closely related proteins responsible for transmission of peptide hormone signals
from the extracellular surface of cells to the nucleus. STAT3 is a master regulator of
most key hallmarks and enablers of cancer, including cell proliferation, resistance to
apoptosis, metastasis, immune evasion, tumor angiogenesis, epithelial mesenchymal
transition (EMT), response to DNA damage, and the Warburg effect. STAT3 also is a key
mediator of oncogene addiction and supports the self-renewal of tumor-initiating cancer
stem cells that contribute to cancer initiation, cancer maintenance, and relapse in
several types of tumors. STAT3 activity is increased in ~50% of all cancers, due either
to naturally occurring STAT3 mutations, as have been demonstrated in human inflammatory
hepatocellular adenomas and large granular lymphocytic leukemia, or, more commonly as a
result of activation of signaling molecules upstream of STAT3, including receptor
tyrosine kinases (RTK; e.g. epidermal growth factor receptor, EGFR), tyrosine
kinase-associated receptors (e.g. the family of IL-6 cytokine receptors or G-protein
coupled receptors, GPCR), and Src kinases (e.g. Src, Lck, Hck, Lyn, Fyn, or Fgr). Thus,
STAT3 is an attractive target for drug development to treat many types of cancer
including breast cancer, head and neck squamous cell carcinoma (HNSCC), non-small cell
lung cancer (NSCLC), hepatocellular carcinoma (HCC), colorectal cancer (CRC), gastric
adenocarcinoma and melanoma.

**Clinical trials are research studies that involve people. These studies test new ways to prevent, detect, diagnose, or treat diseases. People who take part in cancer clinical trials have an opportunity to contribute to scientists’ knowledge about cancer and to help in the development of improved cancer treatments. They also receive state-of-the-art care from cancer experts... Click here to learn more about clinical trials.