Phase 1b/2 Study of TTI-101 in Combination for Patients With Metastatic Hormone Receptor-Positive and HER2-Negative Breast Cancer

Phase 1

Completed

• Conditions: Breast Cancer

• Registration Number: NCT05384119
• Lead Sponsor: Tvardi Therapeutics, Incorporated

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2022-5-17
• Last Update Posted: 2 September 2024

Recruitment & Eligibility

• Status: Completed
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

Inclusion Criteria:<br><br>Participants must meet all the following criteria to be eligible:<br><br> 1. Age =18 years at the time of informed consent.<br><br> 2. Metastatic or locally advanced breast cancer not amenable to curative treatment by<br> surgery or radiotherapy.<br><br> 3. For Phase 1b,currently receiving palbociclib and AI or fulvestrant; for Phase 2,<br> currently receiving palbociclib or ribociclib and AI or fulvistrant therapy in the<br> metastatic setting with evidence of progressive disease. In addition:<br><br> - Must have remained on palbociclib or ribociclib and AI or fulvestrant therapy<br> for =6 months for advanced breast cancer or metastatic disease prior to<br> evidence of progression that in the opinion of the treating physician warrants<br> continued therapy with palbociclib or ribociclib and AI or fulvestrant.<br><br> - Dosage of palbociclib, ribociclib, AI and fulvestrant must remain unchanged<br> from regimen prior to study enrollment specifically palbociclib at a dose of<br> 125, 100, or 75 mg administered orally for 21 days every 28-day cycle or<br> ribociclib at a dose of 200, 400, or 600 mg administered orally for 21 days<br> every 28-day cycle.<br><br> 4. All men and premenopausal women must be on medical gonadal suppression therapy with<br> a gonadotropin analog (e.g, goserelin or leuprolide) and have estrogen levels in the<br> postmenopausal range by institutional criteria at baseline.<br><br> 5. Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.<br><br> 6. Has documented confirmation of histological or cytological HR-positive,<br> HER2-negative breast cancer per local laboratory testing.<br><br> 7. Up to 2 prior lines of systemic treatment (most recent line of therapy must be<br> palbociclib and AI or fulvestrant for Phase 1b and palbociclib or ribociclib and AI<br> or fulvestrant for Phase 2) in the locally advanced or metastatic setting is<br> allowed; the participant must have shown evidence of progressive disease on<br> palbociclib and AI or fulvestrant for Phase 1b and palbociclib or ribociclib and AI<br> or fulvestrant for Phase 2 in the locally advanced or metastatic setting prior to<br> enrollment.<br><br> 8. Willing to provide a representative fresh tumor tissue specimen prior to enrollment.<br> The fresh tumor specimen must be obtained after evidence of progression on<br> palbociclib and AI or fulvestrant for Phase 1b and palbociclib or ribociclib and AI<br> or fulvestrant for Phase 2.<br><br> • Participants with bone only disease WITHOUT a soft tissue component, may opt out<br> of the tumor biopsy.<br><br> 9. The presence of measurable disease as per Response Evaluation Criteria in Solid<br> Tumors (RECIST) Version 1.1 is preferred but not required. Lesions in a previously<br> irradiated area that have not progressed are not considered measurable.<br><br>Exclusion Criteria:<br><br>Participants meeting any of the following exclusion criteria will not be eligible:<br><br> 1. Has received more than 2 lines of prior systemic therapy for locally<br> advanced/metastatic breast cancer.<br><br> 2. Had prior exposure to any signal transducer and activator of transcription 3 (STAT3)<br> inhibitor.<br><br> 3. Had radiotherapy within 3 weeks prior to Cycle 1 Day 1 (cycle is 28 days).<br> Participants must have recovered from radiotherapy toxicities prior to starting<br> study treatment and recovered to Grade 1 or better from related side effects of such<br> therapy (with the exception of alopecia).<br><br> 4. Has HER2 overexpression by local laboratory testing (immunohistochemical [IHC] 3+ or<br> in situ hybridization positive).<br><br> 5. Has known loss of retinoblastoma tumor suppressor gene (Rb) (testing not mandatory).<br><br> 6. Has had disease progression on more than two cyclin-dependent kinase (CDK)4/6<br> inhibitors. Adjuvant abemaciclib is allowed but must have progressed on palbociclib<br> or ribociclib.<br><br> 7. Concurrently using other anticancer therapy. Participants must continue palbociclib<br> and AI or fulvestrant for Phase 1b and palbociclib or ribociclib and AI or<br> fulvestrant for Phase 2.

Exclusion Criteria

Not provided

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Phase 1b: Number of Participants Who Experience a Dose Limiting Toxicity (DLT);Phase 1b: Number of Participants Who Experience an Adverse Event (AE);Phase 1b: Number of Participants Who Experience a Serious Adverse Event (SAE);Phase 2: Landmark Progression Free Sulrvival at 6 Months (PFS6)