Can a STAT3 pill break breast Cancer's resistance to standard treatment?
NCT ID NCT05384119
First seen Sep 24, 2026 · Last updated Sep 25, 2026 · Updated 1 time
Summary
Researchers are testing whether adding an experimental drug called TTI-101 to standard hormone-based therapy can help people with metastatic hormone receptor-positive, HER2-negative breast cancer whose tumors have stopped responding to palbociclib or ribociclib. The trial has two parts: a small safety phase to find the best dose of TTI-101, and a phase 2 part to see if the combination slows tumor growth. Participants must already be taking palbociclib or ribociclib plus an aromatase inhibitor or fulvestrant and have evidence of disease progression.
What this could mean
Our plain-language read of the trial. This is informational only, not medical advice or a prediction.
- Active substance
- TTI-101, an experimental STAT3 inhibitor pill
- What this could lead to
- If TTI-101 helps, it could offer a way to extend the benefit of standard hormone-based breast cancer therapy after tumors stop responding to it.
- What could go wrong
- This is a very small, early-stage trial, so safety and effectiveness are still unknown. Adding TTI-101 could cause side effects or fail to overcome resistance.
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Study facts
What this study's own registry entry says, in plain language.
- Phase
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Phase 1
The first testing in people. Mainly checks safety and dose, usually in a small group.
- Participants
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6 people
The number who actually took part.
- Started
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Jan 2023
- Finished
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May 2024
- Lead sponsor
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A company
The lead sponsor is a pharmaceutical, biotech, or medical-device company.
Who can take part
This study's own entry requirements. Only the study team can say for certain whether you qualify.
- Ages
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18 years and older
- Sex
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Anyone
- Healthy volunteers
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Not accepted
This study is not open to healthy volunteers. The entry requirements below say who it is open to.
Show the full entry requirements Hide the full entry requirements
Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.
Inclusion Criteria: Participants must meet all the following criteria to be eligible: 1. Age ≥18 years at the time of informed consent. 2. Metastatic or locally advanced breast cancer not amenable to curative treatment by surgery or radiotherapy. 3. For Phase 1b,currently receiving palbociclib and AI or fulvestrant; for Phase 2, currently receiving palbociclib or ribociclib and AI or fulvistrant therapy in the metastatic setting with evidence of progressive disease. In addition: * Must have remained on palbociclib or ribociclib and AI or fulvestrant therapy for ≥6 months for advanced breast cancer or metastatic disease prior to evidence of progression that in the opinion of the treating physician warrants continued therapy with palbociclib or ribociclib and AI or fulvestrant. * Dosage of palbociclib, ribociclib, AI and fulvestrant must remain unchanged from regimen prior to study enrollment specifically palbociclib at a dose of 125, 100, or 75 mg administered orally for 21 days every 28-day cycle or ribociclib at a dose of 200, 400, or 600 mg administered orally for 21 days every 28-day cycle. 4. All men and premenopausal women must be on medical gonadal suppression therapy with a gonadotropin analog (e.g, goserelin or leuprolide) and have estrogen levels in the postmenopausal range by institutional criteria at baseline. 5. Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 6. Has documented confirmation of histological or cytological HR-positive, HER2-negative breast cancer per local laboratory testing. 7. Up to 2 prior lines of systemic treatment (most recent line of therapy must be palbociclib and AI or fulvestrant for Phase 1b and palbociclib or ribociclib and AI or fulvestrant for Phase 2) in the locally advanced or metastatic setting is allowed; the participant must have shown evidence of progressive disease on palbociclib and AI or fulvestrant for Phase 1b and palbociclib or ribociclib and AI or fulvestrant for Phase 2 in the locally advanced or metastatic setting prior to enrollment. 8. Willing to provide a representative fresh tumor tissue specimen prior to enrollment. The fresh tumor specimen must be obtained after evidence of progression on palbociclib and AI or fulvestrant for Phase 1b and palbociclib or ribociclib and AI or fulvestrant for Phase 2. • Participants with bone only disease WITHOUT a soft tissue component, may opt out of the tumor biopsy. 9. The presence of measurable disease as per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 is preferred but not required. Lesions in a previously irradiated area that have not progressed are not considered measurable. Exclusion Criteria: Participants meeting any of the following exclusion criteria will not be eligible: 1. Has received more than 2 lines of prior systemic therapy for locally advanced/metastatic breast cancer. 2. Had prior exposure to any signal transducer and activator of transcription 3 (STAT3) inhibitor. 3. Had radiotherapy within 3 weeks prior to Cycle 1 Day 1 (cycle is 28 days). Participants must have recovered from radiotherapy toxicities prior to starting study treatment and recovered to Grade 1 or better from related side effects of such therapy (with the exception of alopecia). 4. Has HER2 overexpression by local laboratory testing (immunohistochemical \[IHC\] 3+ or in situ hybridization positive). 5. Has known loss of retinoblastoma tumor suppressor gene (Rb) (testing not mandatory). 6. Has had disease progression on more than two cyclin-dependent kinase (CDK)4/6 inhibitors. Adjuvant abemaciclib is allowed but must have progressed on palbociclib or ribociclib. 7. Concurrently using other anticancer therapy. Participants must continue palbociclib and AI or fulvestrant for Phase 1b and palbociclib or ribociclib and AI or fulvestrant for Phase 2.
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Conditions
The condition(s) this trial relates to.
As listed by the trial registrant
The condition terms exactly as the trial's registrant entered them.
Contacts and locations
Locations
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Harold C. Simmons Comprehensive Cancer Center
Dallas, Texas, 75390, United States
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Holy Cross Health Fort Lauderdale - Holy Cross Hospital
Fort Lauderdale, Florida, 33308, United States
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Texas Oncology - Dallas Fort Worth (DFW) - Baylor Charles A. Sammons Cancer Center
Dallas, Texas, 75246, United States
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University of Texas MD Anderson Cancer Center
Houston, Texas, 77030, United States
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Vanderbilt - Ingram Cancer Center
Nashville, Tennessee, 37232, United States
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Washington University School of Medicine Siteman Cancer Center
St Louis, Missouri, 63110, United States
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