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

NCT ID: NCT05384119

Last Updated: 2025-02-21

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 6 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-01-09
• Study Completion Date: 2024-04-25

Brief Summary

The primary objective of Phase 1b will be to evaluate the safety and tolerability of TTI-101 when added to palbociclib and AI or fulvestrant administered orally to participants with hormone receptor-positive (HR+) human epidermal receptor 2-negative (HER2)- palbociclib-resistant breast cancer, and to determine the recommended Phase 2 dose (RP2D) for TTI-101 when added to palbociclib and AI or fulvestrant.

The primary objective of Phase 2 will be to evaluate anti-tumor activity in participants who receive TTI-101 added to palbociclib or ribociclib and AI or fulvestrant.

Conditions

Breast Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Phase 1b: Dose Escalation

Participants will receive up to 3 dose levels of TTI-101 added to palbociclib and AI or fulvestrant to determine the RP2D.

Group Type: EXPERIMENTAL

TTI-101

Intervention Type: DRUG

Oral tablet

Palbociclib

Intervention Type: DRUG

Oral capsule

Aromatase inhibitor (AI)

Intervention Type: DRUG

Oral tablet

fulvestrant

Intervention Type: DRUG

Oral tablet

Phase 2: Dose Expansion

Enrollment in Phase 2 may commence with approval from the safety review committee. Participants will be enrolled and treated at the RP2D of TTI-101 added to palbociclib or ribociclib and AI or fulvestrant.

Group Type: EXPERIMENTAL

TTI-101

Intervention Type: DRUG

Oral tablet

Palbociclib

Intervention Type: DRUG

Oral capsule

Aromatase inhibitor (AI)

Intervention Type: DRUG

Oral tablet

fulvestrant

Intervention Type: DRUG

Oral tablet

ribociclib

Intervention Type: DRUG

Oral tablet

Interventions

TTI-101

Oral tablet

Intervention Type: DRUG

Palbociclib

Oral capsule

Intervention Type: DRUG

Aromatase inhibitor (AI)

Oral tablet

Intervention Type: DRUG

fulvestrant

Oral tablet

Intervention Type: DRUG

ribociclib

Oral tablet

Intervention Type: DRUG

Other Intervention Names

Ibrance ®

Eligibility Criteria

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

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Tvardi Therapeutics, Incorporated

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Holy Cross Health Fort Lauderdale - Holy Cross Hospital

Fort Lauderdale, Florida, United States

Washington University School of Medicine Siteman Cancer Center

St Louis, Missouri, United States

Vanderbilt - Ingram Cancer Center

Nashville, Tennessee, United States

Texas Oncology - Dallas Fort Worth (DFW) - Baylor Charles A. Sammons Cancer Center

Dallas, Texas, United States

Harold C. Simmons Comprehensive Cancer Center

Dallas, Texas, United States

University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Countries

United States

Other Identifiers

TVD-101-002B

Identifier Type: -

Identifier Source: org_study_id