1. Written informed consent and any locally required authorization (eg, HIPAA in the
USA) obtained from the patient/legal representative prior to performing any
protocol-related procedures, including screening evaluations.
2. Metastatic or unresectable cancer that expresses KIT. KIT expression must have been
documented in the patient's pathology report. Other patients with KIT positive
cancers will have progressed on at least one prior therapy.
3. For patients with GIST, patients will have progressed on at least one prior tyrosine
kinase inhibitor therapy or be intolerant. If documented to have SDH deficient or
PDGFRA-D842V GIST, no prior therapy is required for study entry.
4. Patients must have at least 1 lesion that is measurable using Response Evaluation
Criteria in Solid Tumors (RECIST) guidelines (v 1.1; Eisenhauer et al, 2009).
5. Age 18 years at the time of study entry.
6. Females must be surgically sterile, one year post menopausal or negative results for
a pregnancy test performed at Screening and agree to use two methods of
contraception; Males who have not had a vasectomy must agree to two methods of
7. Eastern Cooperative Oncology Group (ECOG) status of 0 or 1 (see Appendix 2).
8. Adequate organ function as defined below:
- Hemoglobin 10 g/dL. This criterion must be met without transfusion.
- Absolute neutrophil count 1500/mm3
- Platelet count 100,000/mm3
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) 5
institutional upper limit of normal (ULN) for cases involving liver metastasis
and 2.5 ULN for all other cases
- Bilirubin 1.5 ULN except for cases of documented or suspected Gilbert's
disease, in which bilirubin must be 5 ULN
- Serum creatinine 1.5 g/dL
1. Receipt of anticancer therapy:
- Within 3 weeks prior to the first dose of KTN0158 of any biologic treatment or
- Within 2 weeks prior to the first dose of KTN0158 of any oral therapy or 5.5
half lives whichever is longer or following palliative radiation therapy.
2. Concurrent use of hormones for non-cancer related conditions (eg, insulin for
diabetes and hormone replacement therapy) is acceptable. Concurrent use of
gonadotropin-releasing hormone agonists for prostate cancer is acceptable if the
patient has been on a stable dose for at least 3 months prior to the first dose of
3. Immunosuppressive or systemic steroids medication within 7 days before the first dose
of KTN0158 (inhaled and topical corticosteroids are permitted). Concurrent use of
replacement doses of steroids (defined as 30 mg/day hydrocortisone or the
equivalent) is acceptable if the patient has been on a stable dose for at least 2
weeks prior to the first dose of KTN0158.
4. Known allergy or past administration reaction including infusion reactions,
anaphylactic, or anaphylactoid reactions to any component of the KTN0158 formulation.
5. Symptomatic or untreated central nervous system metastases requiring concurrent
treatment, including but not limited to surgery, radiation, and/or corticosteroids;
if treated, patient must be asymptomatic for 3 months prior to study entry.
6. Other invasive malignancy within 2 years prior to enrollment except for localized
prostate cancer, cervical carcinoma in situ, non-melanomatous carcinoma of the skin,
or ductal carcinoma in situ of the breast that has/have been surgically cured.
7. Unresolved toxicities from prior anticancer therapy, defined as having not resolved
to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI
CTCAE) v 4.03 < Grade 2 or normalized to baseline, or to levels dictated in the
inclusion/exclusion criteria, with the exception of alopecia.
8. Major surgical procedure (as defined by the investigator) within 30 days prior to
Study Day 1 or incomplete recovery from any prior surgery.
9. Pregnancy or breast feeding
10. Uncontrolled intercurrent illness that would limit compliance with study requirements
or compromise the patient such as ongoing or active infection, symptomatic congestive
heart failure, hypertension requiring adjustment of medication, idiopathic and
symptomatic hypotension, unstable angina pectoris, clinically significant cardiac
arrhythmia including atrial fibrillation, active peptic ulcer disease or gastritis
with ongoing blood loss, or psychiatric illness/social situations that would limit
compliance with study requirements or compromise the ability of the patient to give
written informed consent.
11. Any condition that, in the opinion of the investigator, would interfere with
evaluation of the investigational product or interpretation of patient safety or
12. Concurrent enrollment in another clinical study, unless it is an observational
13. Patients with a left ventricular cardiac ejection fraction < 50% as assessed by an
echocardiogram or MUGA scan or prolonged QTc interval of Grade 2 or higher or history
of prolonged QTc interval from other drugs.
Minimum Eligible Age: 18 Years
Maximum Eligible Age: N/A
Eligible Gender: Both