Overview
This study is a Phase III, Randomized, Controlled, Global Multicenter Study to Evaluate the Efficacy and Safety of Oral Tinengotinib versus Physician's Choice in Subjects with Fibroblast Growth Factor Receptor (FGFR)-altered, Chemotherapy- and FGFR Inhibitor-Refractory/Relapsed Cholangiocarcinoma
Description
Approximately 200 subjects will be enrolled. Eligible subjects will be randomized in a 2:2:1 ratio to receive tinengotinib 8 mg QD, tinengotinib 10 mg QD or Physician's Choice in Part A; and eligible subjects will be randomized in a 2:1 ratio to receive the recommended Part B dose or selected dose or Physician's Choice in Part B.
Eligibility
Inclusion Criteria:
- ≥ 18 years of age at the time of signing the informed consent form (ICF).
- Histologically or cytologically confirmed CCA/adenocarcinoma of biliary origin with radiological evidence of unresectable or metastatic disease.
- Documentation of FGFR2 fusion/rearrangement gene status
- Subjects must have received at least one line of prior chemotherapy and exactly one FDA approved FGFR inhibitor.
Exclusion Criteria:
- Prior receipt of two or more FGFR inhibitors, either approved or investigational drugs.
- Subjects with known brain or central nervous system (CNS) metastases that have radiologically or clinically progressed in the 28 days prior to initiation of therapy. Subjects with asymptomatic brain/CNS metastases or treated brain/CNS metastases that have been clinically stable for 14 days on steroids without escalation of steroids are eligible for enrollment.
- Subjects 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, including those that have previously undergone potentially curative therapy.
- Subjects who have received prior systemic therapy or investigational study drug ≤ 5 half-lives or 14 days, whichever is shorter, prior to starting the study drug or who have not recovered (grade ≤ 1 or at pretreatment baseline except tolerable grade 2 alopecia, fatigue/asthenia, and neuropathy due to trauma) from adverse events (AEs) of prior therapy.
- Concurrent anticancer therapy including chemo-, immune-, or radiotherapy. Hormone therapy may be allowed with Sponsor approval.
- Subjects who have received wide field radiotherapy ≤ 4 weeks or limited field radiation for palliation ≤ 2 weeks prior to starting the study drug or who have not recovered from AEs of prior therapy.
- Subjects with uncontrolled hypertension (defined as blood pressure of ≥ 150 mm Hg systolic and/or ≥ 90 mm Hg diastolic despite adequate treatment with antihypertensive medications at screening)