Clinical Trial 21923

• Overview

  Study Title:

  A Phase 1b/2 Multicenter, Open-label Study to Evaluate the Safety and Efficacy of TTI-101 as Monotherapy and in Combination in Participants with Locally Advanced or Metastatic, and Unresectable Hepatocellular Carcinoma

  Summary:

  The purpose of this reach study is to evaluate the safety of TTI-101 when given either alone or in combination treatment, and to see if it will help in the treatment of liver cancer.

  Objective:

  Primary- - To evaluate the safety and tolerability of TTI-101 orally administered as a single agent to participants with locally advanced or metastatic, and unresectable HCC. - To determine the MTD and/or RP2D of TTI-101 as a single agent. Secondary- - To assess the preliminary efficacy of TTI-101 as a single agent in participants with locally advanced or metastatic, and unresectable HCC. - To assess additional efficacy endpoints. - To characterize the plasma PK of TTI-101 following oral administration. - To determine the pharmacodynamics of TTI-101 following oral administration.

• Treatments

  Therapies:

  Chemotherapy (NOS); Immunotherapy; Therapy (NOS)

  Medications:

  Atezolizumab (Tecentriq); Avastin (Bevacizumab); Bevacizumab (); Pembrolizumab (Keytruda); TTI-101 ()

• Inclusion Criteria

  • Able to understand and willing to provide informed consent and able to comply with the study procedures and restrictions.
  • Age >18 years at the time of informed consent.
  • Have histologically or radiographically (Liver Imaging Reporting and Data Systems category 5) confirmed diagnosis of locally advanced or metastatic, and unresectable HCC. Participants without cirrhosis require histological confirmation.
  • Measurable disease as per RECIST Version 1.1.
  • Able to swallow tablets.
  • Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  • Has adequate hematologic and organ function as defined by the protocol at screening
  • Child-Pugh class A or B7 within 7 days prior to enrollment.
  • Females of childbearing potential (ie, ovulating, premenopausal, and not surgically sterile) must: Have a negative serum pregnancy test at screening; Not be breastfeeding or lactating; Agree to use a highly effective method of birth control for the duration of the study and for at least 30 days after the last dose in the study.
  • Males must: Agree to use a condom for at least 30 days after the last dose in the study; agree to abstain from sperm donation; Unless surgically sterile, males with female partners of childbearing potential must agree to use 2 methods of acceptable birth control for at least 30 days after the last dose in the study.
  • Additional Criteria will apply

• Exclusion Criteria

  • Pregnant or breastfeeding.
  • Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC.
  • History of leptomeningeal disease.
  • Previous treatment of the current malignancy with a signal transducer and activator of transcription (STAT) inhibitor.
  • Previous therapy with: Standard therapy including chemotherapy, immunotherapy, biologic therapy, or any other anticancer therapy within 28 days (or 5 elimination half-lives for non-cytotoxics, whichever is shorter) of Cycle 1 Day 1 (6 weeks for nitrosoureas or mitomycin) OR Any investigational agent within 28 days (or 5 elimination half-lives for a non-cytotoxic investigational therapy, whichever is shorter) of Cycle 1 Day 1 or 5 half-lives for a small molecule/targeted therapy.
  • Extensive prior radiotherapy to more than 30% of bone marrow reserves, or prior bone marrow/stem cell transplantation within 5 years from enrollment.
  • Herbal preparations are not allowed throughout the study. These herbal medications include but are not limited to St. John's wort, kava, ephedra (mahung), gingko biloba, dehydroepiandrosterone (DHEA), yohimbe, saw palmetto, and ginseng. Participants should stop using herbal medications 7 days prior to the first dose of study treatment.
  • Is not fully recovered from all coronavirus disease 2019 (COVID-19)-related symptoms for 2 weeks prior to Cycle 1 Day 1, if previously tested positive for COVID-19.
  • Ongoing toxicity (except alopecia) due to a prior therapy, unless returned to baseline or Grade 1 or less.
  • Has had major surgery within 3 weeks prior to starting investigational product (IP) or has not recovered from major side effects due to surgery.
  • Significantly impaired cardiac function
  • History of cerebrovascular accident or stroke within the previous 2 years.
  • History of hepatic encephalopathy.
  • Uncontrolled or symptomatic hypercalcemia
  • Evidence of bleeding diathesis or significant coagulopathy
  • History of Grade 3 or 4 allergic reactions attributed to compounds of similar chemical or biologic composition as TTI-101
  • Known active metastases in the central nervous system
  • History of difficulty swallowing oral medications, malabsorption, or other chronic gastrointestinal disease or conditions that may hamper compliance and/or absorption of the IP
  • Has a known history of human immunodeficiency virus (HIV) infection
  • Participants with chronic hepatitis B virus (HBV) infection, unless screening viral load > History of malignancy other than HCC within 3 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death, such as adequately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, localized prostate cancer, ductal carcinoma in situ, or Stage I uterine cancer.
  • Has any other concurrent severe and/or uncontrolled medical condition that would, in the investigator's judgment, cause unacceptable safety risks, contraindicate participation in the clinical study, or compromise compliance with the protocol
  • Is unable to understand and to comply with study instructions and requirements.
  • Additional Criteria will apply

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