Study to Evaluate the Efficacy and Safety of TT-00420 in Cholangiocarcinoma

1. ≥ 18 years of age, at the time of signing informed consent

2. Histologically or cytologically documented advanced/metastatic or surgically unresectable cholangiocarcinoma who have received at least one line of prior systemic chemotherapy. Patients will be assigned to 1 of 4 cohorts:

3. At least one measurable lesion as defined by RECIST V1.1 criteria for solid tumors5

4. Documentation of FGFR gene alteration status

5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

6. Adequate organ function confirmed at screening and within 10 days of initiating treatment, as evidenced by:

7. Negative pregnancy test within 72 hours before starting study treatment in all premenopausal women and women < 12 months after the onset of menopause

8. Must agree to take sufficient contraceptive methods to avoid pregnancy (including male and female participants) during the study and until at least 6 months after ceasing study treatment

9. Able to sign informed consent and comply with the protocol

1. Women who are pregnant or lactating

2. Women of child-bearing potential (WOCBP) who do not use adequate birth control

3. Patients with untreated brain or central nervous system (CNS) metastases or brain/CNS metastases that have progressed (e.g. evidence of new or enlarging brain metastasis or new neurological symptoms attributable to brain/CNS metastases) Note: Patients with treated brain metastases that are off corticosteroids and have been clinically stable for 28 days are eligible for enrollment.

4. Patients with a known concurrent malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, carcinoma in situ of the cervix or other noninvasive or indolent malignancy that has previously undergone potentially curative therapy.

5. Patients with the following mood disorders as judged by the Investigator or a psychiatrist:

6. Impaired cardiac function or significant diseases, including but not limited to any of the following:

7. Patients with uncontrolled hypertension (defined as blood pressure of ≥ 150 mmHg systolic and/or ≥ 90 mmHg diastolic at Screening)

8. Patients with:

9. Other concurrent severe and/or uncontrolled concomitant medical conditions (e.g. uncontrolled hypertriglyceridemia [triglycerides > 500 mg/dL], or active or uncontrolled infection) that could cause unacceptable safety risks or compromise compliance with the protocol

10. Patients who have received chemotherapy, targeted therapy, or immunotherapy ≤ 5 half-lives or 3 weeks, whichever is shorter, (6 weeks for nitrosourea or mitomycin-C) prior to starting study drug

11. Patients who have received wide field radiotherapy ≤ 4 weeks or limited field radiation for palliation ≤ 2 weeks prior to starting study drug or who have not recovered from adverse events of prior therapy

12. Patients who have undergone major surgery ≤ 4 weeks prior to starting study drug or who have not recovered from adverse events of prior therapy

13. Patients who are currently receiving treatment with therapeutic doses of warfarin sodium (Coumadin®) or any other coumarin-derivative anticoagulants

14. Patients who are currently receiving treatment with strong CYP3A inhibitors or inducers, or sensitive substrates of CYP3A4 ≤ 2 weeks prior to starting study drug.

15. Patients who are using a proton pump inhibitor within 4 days prior to the start of study therapy or a histamine-2 blocker within 2 days prior to the start of study therapy.

16. Known diagnosis of human immunodeficiency virus (HIV) infection (HIV testing is not mandatory; patients with well controlled HIV might be enrolled per investigator's discretion and Sponsor approval)

17. Evidence of active infection with Hepatitis B or Hepatitis C that is not adequately controlled. For patients with known prior history of Hepatitis B or Hepatitis C, enrollment may be allowed per investigator's discretion and Sponsor approval.

18. Inability to swallow or tolerate oral medication

19. Has a history or current evidence of any condition, therapy, or laboratory abnormality that, in the opinion of the investigator, might confound the results of the trial, interfere with the patient's safe participation and compliance in the trial.