Study of Futibatinib in Patients With Advanced Cholangiocarcinoma With FGFR2 Fusion or Rearrangement

Phase 2 Study of Futibatinib 20 mg and 16 mg in Patients With Advanced Cholangiocarcinoma With FGFR2 Fusions or Rearrangements

This is an open-label, multinational, randomized Phase 2 study confirming the clinical benefit of 20 mg futibatinib and evaluating the safety and efficacy of 16 mg futibatinib in previously treated CCA harboring FGFR2 gene fusions and other rearrangements.

This is an open-label, multinational, randomized Phase 2 study confirming the clinical benefit of 20 mg futibatinib and evaluating the safety and efficacy of 16 mg futibatinib in previously treated CCA harboring FGFR2 gene fusions and other rearrangements. Eligible patients will be randomized on a 1:1 basis to the following study arms:

• Patients will receive futibatinib at an oral dose of 16 mg, administered daily (QD) on every day of a 21-day cycle.
• Patients will receive futibatinib at an oral dose of 20 mg, administered daily (QD) on every day of a 21-day cycle.

Patients may continue to receive continuous futibatinib until documentation of progressive disease (PD) per RECIST 1.1, or until other withdrawal criteria are met, whichever comes first.

Inclusion Criteria:

1. Histologically or cytologically confirmed, locally advanced, metastatic, or unresectable intrahepatic of extrahepatic Cholangiocarcinoma.
2. Documented evidence of FGFR2 gene fusions or other FGFR2 rearrangement
3. Received at least one prior systemic gemcitabine and platinum-based regimen for CCA
4. Documentation of radiographic disease progression on the most recent prior therapy
5. Measurable disease
6. performance status 0 or 1
7. Adequate organ function

Exclusion Criteria:

1. History or current evidence of calcium and phosphate homeostasis disorder

2. Current evidence of clinically significant retinal disorder

3. Treatment with any of the following within the specified time frame prior to the first dose of futibatinib:

   1. Major surgery within the previous 4 weeks (the surgical incision should be fully healed prior to the first dose of futibatinib) and radiotherapy for extended field within 4 weeks or limited field radiotherapy within 2 weeks
   2. Patients with locoregional therapy, eg, transarterial chemoembolization (TACE), selective internal radiotherapy (SIRT) or ablation within 4 weeks
   3. Any non investigational anticancer therapy within 3 weeks or have not recovered from side effects of such therapy prior to futibatinib. Endocrine therapy is allowed for patients with breast or prostate cancer
   4. Targeted therapy or immunotherapy within 3 weeks or within 5 half lives Any investigational agent received within 5 half-lives of the drug or 4 weeks, whichever is shorter.
   5. Patients with prior FGFR-directed therapy

4. A serious illness or medical condition(s) including (but not limited to) the following:

   1. Known brain metastasis (not including primary brain tumors) unless patient is clinically stable for ≥1 month
   2. Known acute systemic infection
   3. Myocardial infarction, severe/unstable angina, symptomatic congestive heart failure (New York Heart Association [NYHA] Class III or IV New York Heart Association [NYHA] Classification) within the previous 2 months; if >2 months, cardiac function must be within normal limits and the patient must be free of cardiac-related symptoms
   4. Significant gastrointestinal disorder(s) that could interfere with the absorption of futibatinib.
   5. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that in the judgment of the Investigator would make the patient inappropriate for entry into this study.

5. Known additional malignancy that is progressing or requires active treatment, with the exception of patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or antitumor assessment of the investigational regimen. Exceptions must be discussed with the Sponsor prior to patient enrollment.

6. Pregnant or lactating female.

7. Known hypersensitivity or severe reaction to futibatinib or its excipients.