Clinical Study of WT2725 in Patients With Advanced Malignancies

Part 1 Inclusion Criteria:

• Patient must have an Eastern Cooperative Oncology Group (ECOG) Performance Score of 0, 1, or 2
• Patient must have one of the following histologically or cytologically documented measurable (may be measureable by tumor markers only, such as quantitative RT-PCR for WT1 transcript for AML, or CA-125 for ovarian carcinoma) advanced stage malignancies: non-small cell lung, ovarian, glioblastoma, and AML (not including acute promyelocytic leukemia), known to overexpress the WT1 protein.
• Patient must qualify with a study specific HLA typing assay.
• Haematological parameters:
• Absolute neutrophil count (ANC) ≥ 1,000/μl
• Platelet count ≥ 10.0x10(to the 4th power)/μl (≥ 5.0 x 10(to 4th power)/μl after stem cell transplant)
• Hemoglobin ≥ 9.0 g/dL
• Absolute lymphocyte count (ALC) ≥ 1, 000/μl (≥ 500/μl after stem cell transplant) Note: After completion of dose escalation, patients with AML are not required to meet these hematologic criteria.
• Biochemical Parameters:
• serum creatinine of ≤ 1.5x upper limit of normal (ULN) for the reference lab.
• total bilirubin of ≤ 2.0 mg/dl (≤ 3.0 mg/dl for patients with known Gilbert's syndrome)
• alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 times the ULN for the reference lab
• Patient must have access to archival tumor tissue sample or agree to undergo biopsy after study eligibility has been confirmed to obtain fresh sample for evaluation of WT1 expression. In place of archival tumor tissue samples, subjects with AML should have available a bone marrow aspirate and/or, bone marrow biopsy, with PCR for WT1 transcript performed before the first dose of study drug.

Note: The archived tumor tissue sample does not need to be delivered to the clinical site prior to enrollment of the patient, however its availability should be confirmed through provision of the accession number or other identification number.

Patient Inclusion Criteria - Part 2:

• Patient or his or her legal representatives must give written informed consent and privacy authorization prior to participation in the study.
• Patient must be willing and able to comply with the study procedures and visit schedules and must be able to follow verbal and written instructions.
• Patient must be ≥ 18 years of age.
• Women of childbearing potential and men with female sexual partners of childbearing potential must agree to abstain from sexual intercourse or use a double barrier method to determine if a woman is of childbearing potential (http://www.nccn.org/professionals/physician\_gls/f\_guidelines.asp).
• Patient must have an ECOG Performance Score of 0, 1, or 2 (refer to Appendix II).
• Patient has a life expectancy of at least 4 months.
• Patient must have histologically or cytologically documented measurable (may be measurable by tumor markers only, such as quantitative RT-PCR for WT1 transcript for AML) advanced stage glioblastoma or AML (not including acute promyelocytic leukemia), known to overexpress the WT1 protein. Note: Determination of WT1 expression will not be assessed prior to patient enrollment.
• Patient must have an advanced stage malignancy defined as meeting at least one of the following criteria:
• progressed or recurred despite standard therapy
• no standard therapy exists
• patient is intolerant of standard therapy
• patient is not a candidate for standard therapy
• Patient must be HLA-A*0201+ and/or HLA-A*0206+
• Patient with glioblastoma must have adequate bone marrow and immune reserve, as documented by:
• ANC ≥ 1000/μl (≥ 500/μl after stem cell transplant)
• Platelet count ≥ 10.0 x 1(to the 4th power)/μl (≥ 5.0 x 10(to the 4th power)/μl after stem cell transplant)
• Hemoglobin ≥ 9.0 g/dL
• ALC ≥ 900/μl (Note: Patients with AML are not required to meet these hematologic criteria).
• Patient must have adequate renal function documented by a serum creatinine of ≤ 1.5 times the ULN for the reference lab.
• Patient must have adequate hepatic function documente