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 30 patients will be enrolled in a 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
six 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:
* Non-squamous NSCLC
* 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).
* 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 ⋅ 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 x the 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)