This is a dose-escalation Phase 1 study designed to determine the maximum tolerated dose
(MTD) and/or recommended Phase 2 dose, and the safety profile of CDX-0158 in patients with
KIT-positive advanced solid malignancies refractory to standard therapy or for which no
standard therapy exists.
1. Written informed consent and any locally required authorization (eg, HIPAA) obtained
from the patient/legal representative prior to performing any protocol-related
procedures, including screening evaluations.
2. Metastatic or unresectable cancer that expresses KIT as documented in the patient's
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. Other patients with
KIT positive cancers will have progressed on at least one prior therapy.
4. Patients must have at least 1 lesion that is measurable using RECIST guidelines.
5. Females of childbearing potential who are sexually active with a nonsterilized male
partner must use 2 methods of effective contraception from screening, and must agree
to continue using such precautions for 60 days after the final dose of study
medication. Females of childbearing potential are defined as those who are not
surgically sterile (i.e., bilateral tubal ligation, bilateral oophorectomy, or
complete hysterectomy) or those who are postmenopausal (defined as 12 months with no
menses without an alternative medical cause).
6. Nonsterilized males who are sexually active with a female partner of childbearing
potential must, with their partner, use 2 acceptable methods of effective
contraception from Day 1 through 60 days after receipt of the final dose of study
7. ECOG status of 0 or 1.
8. Adequate organ function as defined below:
- Hemoglobin ≥ 9 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 × upper
limit of normal (ULN) for cases involving liver metastasis and ≤ 2.5 ×ULN for all
- 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 CDX-0158 of any biologic treatment or
- Within 2 weeks prior to the first dose of CDX-0158 of any oral therapy or 5.5
half lives whichever is longer or following palliative radiation therapy.
Concurrent use of hormones for non-cancer related conditions (e.g., insulin for
diabetes and hormone replacement therapy) is acceptable.
2. Requirement for chronic immunosuppressive medication including systemic
corticosteroids above the physiologic dose (30 mg/day hydrocortisone or the
3. Known allergy or past administration reaction including infusion related reaction
(IRRs), anaphylactic, or anaphylactoid reactions to any component of the CDX-0158
4. History of clinically significant allergic reactions or atopic disease that may pose
an increased risk of severe CDX-0158 IRRs.
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 (localized prostate
cancer, cervical carcinoma in situ, non-melanoma skin cancer, or ductal carcinoma in
situ of the breast that has/have been surgically cured would not be exclusionary).
7. Unresolved toxicities from prior anticancer therapy, defined as having not resolved to
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 uncontrolled atrial fibrillation, active peptic ulcer disease or
gastritis with ongoing blood loss, or psychiatric illness/social situations that would
limit compliance or compromise the ability of the patient to give written informed
11. Any condition that, in the opinion of the investigator, would interfere with
evaluation of the study medication or interpretation of patient safety or study
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.