On April 7, 2022 Tvardi Therapeutics, Inc. ("Tvardi"), a privately held, clinical-stage biopharmaceutical company focused on the development of STAT3 inhibitors, reported its collaborators will present preclinical data demonstrating TTI-101 overcomes palbociclib resistance in metastatic breast cancer murine models at the upcoming 2022 Annual Meeting of the American Association for Cancer Research (AACR) (Free AACR Whitepaper) in New Orleans, LA, from April 8th – 13th, 2022 (Press release, Tvardi Therapeutics, APR 7, 2022, View Source [SID1234611596]). The study was led by Khandan Keyomarsi, PhD, Professor of Experimental Radiation Oncology at The University of Texas MD Anderson Cancer Center.
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The studies to be presented demonstrate that the upregulation of the IL-6 / STAT3 pathway plays a critical role in palbociclib (CDK 4/6) resistance in hormone receptor-positive (HR+), HER2-negative (HER2-) metastatic breast cancer. Inhibition of STAT3 with TTI-101 overcomes this resistance. Further, the studies demonstrate that the combination of TTI-101 with palbociclib is synergistic in arresting tumor growth in murine models derived from metastatic breast cancer patients who had developed resistance to palbociclib.
"Palbociclib has proved successful in delaying progression in HR+/HER2- metastatic breast cancer patients; however, ~70% will develop resistance and progress within 1-2 years of treatment. There is a significant unmet need for safe and effective options for those patients who become resistant to palbociclib," said Imran Alibhai, PhD, CEO of Tvardi Therapeutics. "The work by Dr. Keyomarsi and her collaborators builds on their previous publications demonstrating the central role of STAT3 in this patient population and paves the way for clinical studies to investigate TTI-101 in combination with palbociclib."
Details of the presentation are as follows:
Circulating IL-6, an early biomarker in HR+, Her2- metastatic breast cancer patients progressing on CDK4/6 inhibitors
Session and Poster: PO.ET03.04 – Breast Cancer Drug Resistance and Novel Targets: 1774 / 3
Presenter: Nicole Kettner, PhD
Date and Time: Monday, April 11th, 2022, 1:30 – 5:00 PM CT
About TTI-101
TTI-101 is an orally delivered small-molecule that directly binds and subsequently blocks the activation of the STAT3 protein. TTI-101, as a single agent, is currently being studied in a multicenter Phase 1 trial of patients with advanced solid tumors who have failed all lines of therapy. To date, TTI-101 has been well-tolerated and has demonstrated clinical activity across a broad range of tumors including multiple durable radiographic objective responses. For more information on this ongoing clinical trial of TTI-101, please visit Clinical Trials.