A PHASE 2 STUDY OF FUTIBATINIB IN PATIENTS WITH SPECIFIC FGFR ABERRATIONS

1. Provide documented informed consent
2. >=18 years of age (or meets the country's regulatory definition for
legal adult age, whichever is greater)
3. Eastern Cooperative Oncology Group (ECOG) performance status 0 or
1
4. Has recovered from the acute toxic effects of prior anticancer therapy
to baseline or Grade 1 (except toxicities which are not clinically
significant such as alopecia)
5. Known FGFR aberration status and tumor type that meet all of the
criteria for one of the following cohorts:
a. Cohort A
I. Histologically-confirmed, locally-advanced, advanced, or metastatic
solid tumors harboring a FGFR1-4 rearrangement determined in tumor
tissue using next-generation sequencing (NGS), fluorescence in situ
hybridization (FISH), or other assays that can determine gene
rearrangements in tumor tissues. Patients with primary brain tumor or
iCCA are not eligible.
ii. Measurable disease per RECIST 1.1
iii. Had disease progression/recurrence after standard treatment for
their advanced or metastatic cancer
b. Cohort B
I. Histologically-confirmed, locally-advanced, advanced, or metastatic
gastric or GEJ adenocarcinoma harboring a FGFR2 amplification. The
tumor must have an FGFR2/CEN10 ratio of >=5 or an FGFR2 copy number
>=10 signals per cell determined in tumor tissue using NGS, FISH, or
other assays that can determine gene amplification in tumor tissues.
ii. Measurable disease per RECIST 1.1
iii. Received at least 2 prior systemic regimens for advanced/metastatic
disease
iv. Experienced disease progression/recurrence during or after the most
recent prior systemic treatment for advanced/metastatic gastric or GEJ
cancer
c. Cohort C
I. Confirmed MLN with a FGFR1 rearrangement as defined by WHO
criteria
ii. Not a candidate for hematological stem cell transplant (HSCT) or
relapsed after HSCT and donor lymphocyte infusion, and progressed and
not a candidate for other therapies
6. Has archival or fresh tumor tissue (preferably in block format) for
Cohorts A and B and bone marrow tissue for Cohort C available to send
to central laboratory.
7. Adequate organ function as defined by the following criteria:
a. Cohorts A and B:
I. Absolute neutrophil count (ANC) >= 1.0 x 10^9/L
ii. Platelet count >= 75,000/mm3 (>= 75 x 10^9/L)
iii. Hemoglobin >= 9.0 g/dL
iv. Alanine aminotransferase (ALT) and aspartate aminotransferase
(AST) <= 3.0 × upper limit of normal (ULN); if liver function abnormalities
are due to underlying liver metastasis, AST and ALT <= 5.0 × ULN.
v. Total bilirubin <= 1.5 × ULN, or <= 3.0 × ULN for patients with Gilbert's
syndrome.
vi. Creatinine clearance (CrCl) (calculated or measured value): >=40
mL/min. For calculated CrCl, use the Cockcroft-Gault formula (Section
6).
vii. Phosphorus <1.5 ULN
b. Cohort C
I. ALT and AST <= 3.0 × ULN; if liver function abnormalities are due to
underlying liver metastasis, AST and ALT <= 5.0 × ULN.
ii. Total bilirubin <= 1.5 × ULN, or <= 3.0 × ULN for patients with Gilbert's
syndrome.
iii. CrCl (calculated or measured value): >=40 mL/min. For calculated
CrCl, use the Cockcroft-Gault formula (Section 6).
iv. Phosphorus <1.5 ULN
8. Women of child-bearing potential (WOCBP) must have a negative
serum pregnancy test prior to administration of the first dose of
futibatinib. Female patients are not considered to be of child-bearing
potential if they are post-menopausal, defined as no menses for 12
months without an alternative medical cause or permanently sterile
(hysterectomy, bilateral salpingectomy, or bilateral oophorectomy).
9. Both males and females of reproductive potential must agree to use
effective birth control during the study prior to the first dose and for 90
days after the last dose or longer based on local requirements.
10. Ability to take medications orally (feeding tube is not permitted).
11. Willing and able to comply with scheduled visits and study
procedures.

1. Currently receiving an investigational drug in a clinical trial or
participating in any other type of medical research judged not to be
scientifically or medically compatible with this study. If a patient is
currently enrolled in a clinical trial involving non-approved use of a device,
then agreement with the investigator and the Sponsor's Medical monitor is
required to establish eligibility.
2. History and/or current evidence of any of the following disorders:
a. Non-tumor related alteration of the calcium-phosphorus homeostasis that is
considered clinically significant in the opinion of the Investigator
b. Ectopic mineralization/calcification including, but not limited to, soft
tissue, kidneys, intestine, or myocardia and lung, considered clinically
significant in the opinion of the Investigator
c. Retinal or corneal disorder confirmed by retinal/corneal examination and
considered clinically significant in the opinion of the Investigator.
3. Corrected QT interval using Fridericia's formula (QTcF) >470 msec. Patients
with an atrioventricular pacemaker or other condition (for
example, right bundle branch block) that renders the QT measurement invalid are
an exception and the criterion does not apply.
4. Treatment with any of the following within the specified time frame prior to
the first dose of futibatinib:
a. Major surgery within 4 weeks (surgical incision should be fully healed)
b. Radiotherapy for extended field within 4 weeks or limited field radiotherapy
within 2 weeks
c. A drug that has not received regulatory approval for any indication within
14 or 21 days of treatment for a nonmyelosuppressive or
myelosuppressive agent, respectively.
5. Received strong inhibitors or inducers of CYP3A4 within 2 weeks of first dose
6. Prior treatment with an FGFR inhibitor
7. A serious illness or medical condition(s) including, but not limited to, the
following:
a. Known acute systemic infection
b. Myocardial infarction, severe/unstable angina, or symptomatic congestive
heart failure within the previous 6 months
c. History or current evidence of uncontrolled ventricular arrhythmia
d. Chronic diarrhea diseases considered to be clinically significant in the
opinion of the Investigator
e. Congenital long QT syndrome, or any known history of torsade de pointes, or
family history of unexplained sudden death
f. Other severe acute or chronic medical or psychiatric condition or laboratory
abnormality that may increase the risk associated with study participation or
futibatinib administration, or may interfere with the interpretation of study
results, and in the judgment of the Investigator would make the patient
inappropriate for entry into this study
8. Active central nervous system (CNS) metastasis and/or carcinomatous
meningitis. Patients with previously treated brain
metastases that are clinically and radiologically stable (for at least 4 weeks
prior to enrollment) are eligible.
9. Known additional malignancy that is progressing or has required active
treatment within the past 2 years. Patients with basal cell
carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in
situ (eg, breast carcinoma, cervical cancer in situ) that have
undergone potentially curative therapy are not excluded.
10. Pregnant or breastfeeding.