A Phase 1, Open-label, Dose-escalation and Expansion Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of CDX-0158 in Adult Patients With KIT Positive Advanced Solid Tumors.
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.
• 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.
• Metastatic or unresectable cancer that expresses KIT as documented in the patient's pathology report.
• 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.
• Patients must have at least 1 lesion that is measurable using RECIST guidelines.
• 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).
• 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 medication.
• ECOG status of 0 or 1.
• 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 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