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

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


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.


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.