This study will determine the safety and maximum tolerated dose of ONO-7579 in patients with
advanced solid tumors, and evaluate efficacy of ONO-7579 in patients with advanced solid
tumors harboring NTRK gene fusions.
Inclusion Criteria (Parts A and B):
1. Male or female aged at least 18 years or older, at the time of signing the informed
2. The patient (or their legal representative) has provided written informed consent,
which signifies an agreement to enter the study and comply with the restrictions and
requirements listed in the informed consent form.
3. ECOG performance status ≤ 2
4. Life expectancy of at least 3 months
5. Patients must have measurable disease, according to RECIST 1.1 (defined as at least
one lesion that can be accurately measured in at least one dimension (longest
diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as ≥
20 mm (≥2 cm) with conventional techniques or as ≥10 mm (≥1 cm) with spiral CT scan),
or RANO criteria for Glioma.
6. Patients must have received at least one prior line of therapy appropriate for their
tumor type and stage of disease. For glioma, patient must have received at least one
prior treatment with radiotherapy and temozolomide. Prior treatment of any Trk
inhibitor(s) is not an exclusion.
7. Adequate hematologic, hepatic and renal function as defined by the following
- Absolute Neutrophil count ≥ 1.5x109
- Platelet count ≥ 75,000 / mm3
- Hemoglobin level ≥ 9.0 g/dL
- Total Bilirubin level ≤ 1.5 X ULN
- AST and ALT ≤ 3 X ULN
- Creatinine clearance* ≥50 mL/min *estimated CLcr by the Cockcroft-Gault equation
8. Women of:
1. Childbearing potential must have a negative serum pregnancy test documented
within 14 days prior to enrollment, and must agree to use two adequate methods
of contraception from Day 1 of the study until 3 months after the end of
treatment. Acceptable forms of effective contraception include;
- Established use of oral, injected or implanted hormonal methods of
- Placement of an intrauterine device or intrauterine system.
- Barrier methods of contraception: condom or occlusive cap (diaphragm or
cervical/vault caps) with spermicidal foam/gel/film/cream/suppository.
- Male sterilization (with the appropriate post-vasectomy documentation of
the absence of sperm in the ejaculate).
2. Non-childbearing potential, defined as pre-menopausal females with a documented
tubal ligation or hysterectomy; or postmenopausal defined as 12 months of
spontaneous amenorrhea with follicle-stimulating hormone (FSH) >40 MlU/mL).
Females on hormone replacement therapy (HRT) will be required to use one of the
contraception methods in Inclusion criteria 8a or must discontinue HRT to allow
confirmation of post-menopausal status prior to being enrolled in the study.
Following confirmation of their post-menopausal status, they can resume HRT
during the study and will not be required to use contraception.
9. A male patient is eligible to participate if he is not trying to father a child and
is willing to use one of the relevant contraception methods as in inclusion criterion
8a from Day 1 of the study until 3 months after the end of treatment.
10. Able to swallow tablets
11. Patients must be recovered to Grade 1 from the effects (excluding alopecia) of any
prior therapy for their malignancies.
Additional Criterion for Part A only
12. Patients with histologically/cytologically confirmed advanced solid tumors, and
documented tumor progression for whom no further standard anticancer treatment is
13. Patients must be able to comply with the protocol requirements regarding fasting, as
determined by the investigator (excluding patients in food assessment cohort(s)).
Additional Criteria for Part B only
14. Patients with histologically/cytologically confirmed advanced solid tumors and
documented tumor progression for whom no further standard anticancer treatment exists
or where, in the opinion of the investigator, the existing standard anticancer
treatment options available are not expected to provide a reasonable benefit to the
15. Patients must have NTRK1, NTRK2 or NTRK3 gene fusion confirmed locally prior to first
1. Radiotherapy within two weeks prior to study entry
2. Major surgery (excluding placement of vascular access) within 4 weeks before the
first dose of study treatment
3. Spinal cord compression or brain metastases unless treated and radiologically stable
for >6 weeks post treatment and not requiring steroids for at least 4 weeks prior to
start of study treatment
4. As judged by the Investigator, any evidence of severe or uncontrolled psychiatric
disease or systemic diseases, including history of suicide attempt or current
suicidal ideation or behavior, active infection including hepatitis B, hepatitis C
and human immunodeficiency virus (HIV). Screening for chronic conditions is not
5. Concurrent treatment with another investigational agent or participated in another
investigational trial within 30 days of study entry
6. Diagnosed or treated for a malignancy other than the tumor under investigation in the
study within 5 years, or who were previously diagnosed with a malignancy other than
that required for the study and have any radiographic or biochemical marker evidence
of that malignancy. Patients with completely resected basal cell carcinoma, squamous
cell carcinoma of the skin, or in situ malignancy are not excluded.
7. Clinically significant cardiovascular disease, including:
- History of myocardial infarction, acute coronary syndromes (including unstable
angina), or coronary angioplasty/stenting/bypass grafting within the past 6
- History of Class III or IV heart failure as defined by the New York Heart
Association (NYHA) functional classification system
- Severe cardiac arrhythmia requiring medication or other severe conduction
abnormalities (e.g. clinically significant QT prolongation or Torsade de
- Uncontrolled hypertension
- Clinically significant valvular disease, cardiomegaly, ventricular hypertrophy,
8. QT prolongation defined as a QTcF interval >470 msec or other significant ECG
abnormalities including 2nd degree (type II) or 3rd degree AV block or bradycardia
(ventricular rate <50 beats/min) on 12-lead ECG at screening
9. Serious concurrent medical conditions, including serious active infection, in the
opinion of the investigator
10. Female patients who are pregnant or breast feeding