A Phase I open-label study of the safety and pharmacokinetics of escalating doses of DNIB0600A in patients with non-small cell lung cancer and platinum-resistant ovarian cancer
Study DnB4987g is a Phase i, multicenter, open-label, dose-escalation study of DniB0600a administered as a single agent by iV infusion to patients with non-squamous nSCLC or non-mucinous, platinum-resistant ovarian cancer. The study will employ a traditional 3 + 3 design to determine the MTD, followed by a cohort expansion at the recommended Phase ii dose, at or below the MTD, to further characterize the safety and activity of DniB0600a.
approximately 20 - 40 patients will be enrolled in the dose-escalation cohorts. additionally, up to 50 patients will be enrolled in two lung cancer dose-expansion cohort, and up to 16 patients will be enrolled in an ovarian cancer
dose-expansion cohort. This trial will be conducted at approximately three to ten investigative sites in the united States.
Patients must meet the following criteria to be eligible for study entry:
* Signed Informed Consent Form
* Age >=18 years
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Histologic documentation of incurable, locally advanced or metastatic disease that has failed prior chemotherapy and for which no standard therapy exists, including the following:
a) Non-squamous NSCLC
b) Non-mucinous, platinum-resistant ovarian cancer (i.e., epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer with documented radiographic progression or relapse according to RECIST within 6 months of receiving platinum-based chemotherapy).
c) Note: Review of NaPi2b expression in patient tumor samples and response measures will be performed on an ongoing basis; on the basis of a review of the data with study investigators in the expansion cohort, enrollment may be restricted to patients with tumors demonstrating NaPi2b IHC overexpression. In this setting, demonstration of NaPi2b overexpression by IHC should be confirmed prior to conducting other study procedures (i.e., laboratory and imaging studies). For patients in the second lung cancer dose-expansion cohort, enrollment will be restricted to patients with tumors demonstrating NaPi2b IHC overexpression (i.e., IHC 2 + or 3+ ).
* Availability and willingness to provide an adequate archival sample of tumor (paraffin tissue block or at least 10 unstained slides)
* For each patient in the study, the availability of an archival tumor biopsy specimen must be verified prior to enrollment.
* Measurable disease is defined as at least one bi-dimensionally
* Measurable -- Non-lymph node lesion >=1 cm on long access diameter on spiral CT scan OR at least one bi-dimensionally measureable lymph node measuring >=1.5 cm on short access diameter on spiral CT scan.
* Absolute neutrophil count >=1500/[MICRO-SYMBOL]L, hemoglobin >=9 g/dL, and platelet count
* Absolute neutrophil count must be assessed >=14 days after the last growth factor support; hemoglobin and platelet count must be assessed >=14 days after the time of prior transfusion.
* Total bilirubin <=1.5 x the upper limit of normal (ULN); AST and ALT <=2.5 x
* Patients with known Gilbert[Single Quote]s disease who have serum bilirubin <=3 x ULN
may be enrolled.
* Serum creatinine <=1.5 xthe ULN or creatinine clearance >=50 mL/min based on a 24-hour urine collection
* International normalized ratio (INR) <=1.5 x the ULN and activated partial thromboplastin time (aPTT) <=1.5x the ULN
* For fertile men or women of childbearing potential, documented willingness to use a highly effective means of contraception (e.g., hormonal methods [implants, injectables, or combined oral contraceptives], intrauterine devices [IUDs], sexual abstinence, or vasectomy/surgical sterilization of patient or partner)