Actively Recruiting
A Study of TTI-101 as Monotherapy and in Combination in Participants With Locally Advanced or Metastatic, and Unresectable Hepatocellular Carcinoma
Led by Tvardi Therapeutics, Incorporated · Updated on 2026-04-27
193
Participants Needed
21
Research Sites
206 weeks
Total Duration
On this page
AI-Summary
What this Trial Is About
The primary objectives of Cohort A Phase 1b and exploratory expansion are to evaluate the safety and tolerability of TTI-101 orally administered as a single agent to participants with locally advanced or metastatic, and unresectable Hepatocellular Carcinoma (HCC) and to determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of TTI-101 as a single agent. The primary objectives of Cohort A Phase 2 are to evaluate the safety and tolerability of TTI-101 orally administered as a single agent at the RP2D to participants with locally advanced or metastatic, and unresectable HCC and to assess the preliminary efficacy of TTI-101 as a single agent in participants with locally advanced or metastatic, and unresectable HCC. The secondary objectives of Cohort A Phase 2 are to assess response, progression, survival, and pharmacokinetics. The primary objectives of Cohorts B and C Phase 1b are to evaluate the safety and tolerability of TTI-101 orally administered in combination with pembrolizumab therapy (Cohort B) and in combination with atezolizumab and bevacizumab therapy (Cohort C) to participants with locally advanced or metastatic, or unresectable HCC and to determine the MTD and/or RP2D of TTI-101 when used in combination with pembrolizumab therapy (Cohort B) and in combination with atezolizumab and bevacizumab therapy (Cohort C). The primary objectives of Cohorts B and C Phase 2 are to evaluate the safety and tolerability of TTI-101 orally administered in combination with pembrolizumab therapy (Cohort B) and in combination with atezolizumab and bevacizumab therapy (Cohort C) at the RP2D to participants with locally advanced or metastatic, and unresectable HCC and to assess the preliminary efficacy of TTI-101 in combination with pembrolizumab therapy (Cohort B) and in combination with atezolizumab and bevacizumab therapy (Cohort C) to participants with locally advanced or metastatic, and unresectable HCC. The secondary objectives of Cohorts B and C Phase 2 are to assess response, progression, survival, and pharmacokinetics.
CONDITIONS
Official Title
A Study of TTI-101 as Monotherapy and in Combination in Participants With Locally Advanced or Metastatic, and Unresectable Hepatocellular Carcinoma
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Able to understand and willing to provide informed consent and comply with study procedures
- Age 18 years or older at consent
- Confirmed diagnosis of locally advanced or metastatic, unresectable Hepatocellular Carcinoma (HCC); histological confirmation required if no cirrhosis
- Cohorts A and B: Willing to provide fresh tumor tissue after prior therapy progression; no biopsy required for Cohort C
- Measurable disease according to RECIST Version 1.1
- Able to swallow tablets
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Adequate blood counts and organ function per specified lab values
- Prothrombin time/international normalized ratio (PT/INR) and activated partial thromboplastin time (aPTT) within 2 times upper limit of normal, except if on anticoagulation
- Child-Pugh class A or B7 within 7 days before enrollment
- Females of childbearing potential must have negative pregnancy test, not be breastfeeding, and agree to use effective contraception during and 30 days after study
- Males must agree to use condoms and abstain from sperm donation for 30 days after last dose; use effective contraception if partner is of childbearing potential
- Cohort A: Must have shown progression on up to 3 prior systemic antitumor therapies
- Cohort B: Must have shown progression after at least 2 cycles of first-line anti-PD-1 or anti-PD-L1 therapy; no more than one prior systemic therapy
- Cohort B: Agree to contraception for at least 4 months after last pembrolizumab dose
- Cohort C: Must be treatment-naïve for locally advanced or metastatic unresectable HCC
- Cohort C: Have had gastroduodenoscopy for varices within 6 months before starting bevacizumab
- Cohort C: Agree to contraception for at least 5 months after last atezolizumab dose and 6 months after last bevacizumab dose
You will not qualify if you...
- Pregnant or breastfeeding
- Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC
- History of leptomeningeal disease
- Previous treatment with a STAT inhibitor
- Prior anticancer therapy within specified recent timeframes before study start
- Extensive prior radiotherapy to >30% bone marrow or bone marrow/stem cell transplant within 5 years
- Use of herbal medications not allowed during study
- Not fully recovered from COVID-19 symptoms for 2 weeks before treatment
- Ongoing toxicity from prior therapy except alopecia unless resolved to baseline or Grade 1 or less
- Major surgery within 3 weeks before treatment or unrecovered from surgery side effects
- Significant heart conditions including recent myocardial infarction, serious arrhythmias, or low heart function
- Pleural, pericardial effusions or ascites requiring frequent drainage
- Recent cerebrovascular accident or stroke within 2 years
- History of hepatic encephalopathy
- Uncontrolled or symptomatic hypercalcemia
- Bleeding disorders without anticoagulation
- Severe allergic reactions to drugs like TTI-101
- Active or unstable central nervous system metastases
- Difficulty swallowing or gastrointestinal conditions affecting drug absorption
- HIV infection
- Chronic hepatitis B with high viral load unless stable on therapy; chronic hepatitis C allowed with conditions
- Other recent malignancies except low-risk types
- Severe or uncontrolled medical conditions that increase safety risks
- Inability to understand or comply with study requirements
- Cohort B: Discontinued prior anti-PD-1/PD-L1 therapy for reasons other than progression
- Cohort C: Uncontrolled high blood pressure
- Cohort C: Prior systemic chemotherapy for target HCC except completed adjuvant/neoadjuvant over 6 months ago
- Cohort C: Untreated or high-risk esophageal or gastric varices
- Cohort C: Significant proteinuria unless confirmed low in 24-hour urine
- Cohort C: Recent use of certain anticoagulant or antiplatelet drugs
- Cohort C: Recent minor surgery before bevacizumab
- Cohort C: History of gastrointestinal perforation
- Cohort C: Tumor involvement of major airways or blood vessels except portal or hepatic veins
- Cohort C: Recent serious cardiovascular or thromboembolic events
- Cohort C: History of fistula
- Cohorts B and C: Recent live vaccine or immune-mediated diseases with some exceptions
- Cohorts B and C: History of lung inflammation or active pneumonitis
- Cohorts B and C: Recent immunosuppressive treatment except low-dose corticosteroids
- Cohorts B and C: Active tuberculosis or recent severe infection
- Cohorts B and C: Recent therapeutic antibiotics use
- Cohorts B and C: Prior allogeneic stem cell or organ transplant
- Cohorts B and C: Severe allergic reactions to similar antibodies or fusion proteins
AI-Screening
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Trial Site Locations
Total: 21 locations
1
The Kirklin Clinic of University of Alabama Birmingham Hospital
Birmingham, Alabama, United States, 35233
Actively Recruiting
2
University of California San Diego
La Jolla, California, United States, 92093
Completed
3
Norris Comprehensive Cancer Center
Los Angeles, California, United States, 90033
Actively Recruiting
4
University of California Irvine Medical Center
Orange, California, United States, 92868
Actively Recruiting
5
University of Colorado Hospital - Anschutz Medical Campus
Aurora, Colorado, United States, 80045
Actively Recruiting
6
Georgetown Lombardi Comprehensive Cancer Center
Washington D.C., District of Columbia, United States, 20007
Completed
7
Moffitt Cancer Center
Tampa, Florida, United States, 33612
Actively Recruiting
8
The Sidney Kimmel Comprehensive Cancer Center
Baltimore, Maryland, United States, 21231
Actively Recruiting
9
University of Michigan Rogel Cancer Center
Ann Arbor, Michigan, United States, 48109
Actively Recruiting
10
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, United States, 48201
Actively Recruiting
11
Washington University in St. Louis
St Louis, Missouri, United States, 63129
Actively Recruiting
12
Memorial Sloan Kettering Cancer Center - New York
New York, New York, United States, 10065
Actively Recruiting
13
Cleveland Clinic Lerner College of Medicine
Cleveland, Ohio, United States, 44195
Actively Recruiting
14
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, United States, 73104
Actively Recruiting
15
Harold C. Simmons Comprehensive Cancer Center
Dallas, Texas, United States, 75390
Actively Recruiting
16
University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030-4000
Actively Recruiting
17
DHR Health Institute for Research and Development
McAllen, Texas, United States, 78504
Actively Recruiting
18
University of Texas Health Science Center - San Antonio
San Antonio, Texas, United States, 78229
Actively Recruiting
19
Virginia Mason Medical Center
Seattle, Washington, United States, 98101
Actively Recruiting
20
Summit Cancer Centers - North Spokane
Spokane, Washington, United States, 99208
Actively Recruiting
21
Froedtert and Medical College of Wisconsin
Milwaukee, Wisconsin, United States, 53226
Completed
Research Team
K
Kari Anne Rowland, MS
CONTACT
S
Sara Manning
CONTACT
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NON_RANDOMIZED
Model
PARALLEL
Primary Purpose
TREATMENT
Number of Arms
3
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