A Phase 1 Study of BLU-285 in Patients with Gastrointestinal Stromal Tumors (GIST) and other Relapsed and Refractory Solid Tumors

1. Patient is *18 years of age.
2. For Part 1: Histologically- or cytologically-confirmed diagnosis of
unresectable GIST or another advanced solid tumor. Patients with unresectable
GIST must have disease that has progressed following imatinib and at least 1 of
the following: sunitinib, regorafenib, sorafenib, dasatinib, pazopanib or an
experimental agent that targets KIT, or disease with a D842 mutation in the
PDGFR* gene. Patients with an advanced solid tumor other than GIST must have
relapsed or refractory disease without an available effective therapy.
- At daily doses <100 mg QD patients may have the diagnosis of either GIST
or a relapsed or refractory solid tumor.
- At daily doses *100 mg QD, at least 2 patients in a cohort (4 patients if the
cohort is expanded) must have the diagnosis of GIST., 3. For Part 2:
- Group 1: Patients must have a confirmed diagnosis of unresectable GIST that
has progressed following imatinib and at least 1 of the following: sunitinib,
regorafenib, sorafenib, dasatinib, pazopanib, or an experimental agent that
targets KIT, and the patient does not have a known D842 mutation in PDGFR*.
- Group 2: Patients must have a confirmed diagnosis of unresectable GIST with
a D842 mutation in the PDGFR* gene. The PDGFR* mutation will be identified by
local or central assessment, either in an archival tissue sample or a new tumor
biopsy.
- Groups 1 and 2: At least 1 measurable lesion defined by the mRECIST 1.1 for
patients with GIST.
- Groups 1 and 2: A tumor sample (archival tissue or a new tumor biopsy) has
been submitted for mutational testing.
4. Patient has Eastern Cooperative Oncology Group (ECOG) performance status
(PS) of 0-2., 5. Patient or legal guardian, if permitted by local regulatory
authorities, provides informed consent to participate in the study.

1. Patient has any of the following within 14 days prior to the first dose of
study drug:
a. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) > 3
× upper limit of normal (ULN) if no hepatic metastases are present; > 5 ×
ULN if hepatic metastases are present.
b. Total bilirubin > 1.5 × ULN; >3 × ULN with direct bilirubin >1.5 ×
ULN in the presence of Gilbert*s Disease.
c. Estimated (Cockcroft-Gault formula) or measured creatinine clearance <40
mL/min.
d. Platelet count < 90 × 10e9/L.
e. Absolute neutrophil count (ANC) < 1.0 ×10e9/L.
f. Hemoglobin (Hgb) < 9 g/dL. Transfusion and erythropoietin may be used to
reach at least 9 g/dL, but must have been administered at least 2 weeks prior
to the first dose of study drug., 2. Patient received a prior anti-cancer
drug less than 5 half-lives or 14 days (whichever is shorter) prior to the
first dose of study drug., 3. Patient has received neutrophil growth factor
support within 14 days of the first dose of study drug., 4. Patient requires
therapy with a concomitant medication that is a strong inhibitor or strong
inducer of cytochrome P450 34A. (see Appendix 2 of the protocol), 5. Patient
has had a major surgical procedure (minor surgical procedures such as central
venous catheter placement, tumor needle biopsy, and feeding tube placement are
not considered major surgical procedures) within 14 days of the first dose of
study drug., 6. Patient has a history of another primary malignancy that has
been diagnosed or required therapy within 1 year prior to the first dose of
study drug. (The following are exempt from the 1-year limit: completely
resected basal cell and squamous cell skin cancer, curatively treated localized
prostate cancer, and completely resected carcinoma in situ of any site.), 7.
Patient has QT interval corrected using Fridericia*s formula (QTcF) > 450
milliseconds., 8. Patient has a history of a seizure disorder (e.g.,
epilepsy) or requirement for anti-seizure medication., 9. Patient has a
history of a cerebrovascular accident or transient ischemic attacks within 1
year prior to the first dose of study drug. , 10. Patient has a known risk of
intracranial bleeding, such as a brain aneurysm or history of subdural or
subarachnoid bleeding., 11. Patient has a primary brain malignancy or
metastases to the brain., 12. Patient has clinically significant,
uncontrolled, cardiovascular disease, including congestive heart failure Grades
II, III or IV according to the New York Heart Association (NYHA)
classification, myocardial infarction or unstable angina within the previous 6
months, or poorly controlled hypertension., 13. Patient has a known diagnosis
of human immunodeficiency virus infection or active viral hepatitis; viral
testing is not required., 14. Patient is unwilling or unable to comply with
scheduled visits, drug administration plan, laboratory tests, or other study
procedures and study restrictions., 15. Women who are unwilling, if not
postmenopausal or surgically sterile, to abstain from sexual intercourse or
employ highly effective contraception during the study drug administration
period and for at least 30 days after the last dose of study drug. , 16.
Pregnant women, as documented by a serum beta human chorionic gonadotropin (*
hCG) pregnancy test consistent with pregnancy obtained within 7 days prior to
the first dose of study drug. Women with *-hCG values that are within the range
for pregnancy but are not pregnant (false-positives) may be enrolled with
written consent of the Sponsor after pregnancy has been excluded. Women of
non-childbearing potential (postmenopausal; hysterectomy; bilateral
salpingectomy; or bilateral oophorectomy) do not require a serum *-hCG
pregnancy test., 17. Women who are breast feeding., 18. Patient has a prior
or ongoing clinically significant illness, medical condition, surgical history,
physical finding, or laboratory abnormality that, in the Investigator*s
opinion, could affect the safety of the patient, alter the absorption,
distribution, metabolism or excretion of the study drug, or impair the
assessment of study results.