A Trial of PDL192 in Subjects With Advanced Solid Tumors

A Phase 1, Multicenter, Open-Label, Dose Escalation Trial of PDL192 in Subjects With Advanced Solid Tumors

This is a phase 1, multicenter, open-label, dose escalation trial of PDL192 in subjects with advanced solid tumors.

The primary study objective is to determine the maximum tolerated dose of PDL192 in subjects with advanced solid tumors.

Inclusion Criteria

Eligible subjects will be considered for inclusion in this study if they meet all of the following criteria:

1. Male or female, 18 years of age or older.
2. Subjects with documented advanced solid tumors.
3. Subjects who have previously failed all standard therapies or subjects who have a tumor where no standard therapy exists.
4. A negative serum pregnancy test (women of childbearing potential only) at screening. Male or female subjects of reproductive potential must be willing to use adequate contraception during the duration of the study and for a minimum of 3 months after the end of treatment.
5. Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information (in accordance with national and local subject privacy regulations).

Exclusion Criteria

Subjects will be ineligible for this study if they meet any one of the following criteria:

1. Symptomatic and progressive central nervous system (CNS) metastases or leptomeningeal metastases

2. Diagnosis of glioblastoma

3. Eastern Cooperative Oncology Group (ECOG) performance status >= 2

4. Abnormal hematologic values defined as:

   • Hemoglobin level < 9 g/dL
   • Absolute neutrophil count (ANC) < 1500/mm3
   • Platelet count < 100,000/mm3

5. Abnormal kidney, liver, or pancreatic function defined as:

   • Serum creatinine > 1.5 x upper limit of normal value (ULN)
   • Aspartate transaminase or alanine transaminase levels of > = 2.5 x ULN
   • Bilirubin > ULN
   • Amylase > 1.5 x ULN
   • Lipase > 1.5 x ULN

6. Known chronic viral hepatitis

7. History of cirrhotic liver disease

8. History of pancreatitis (patients with history of gall stone pancreatitis who are status post-cholecystectomy will be eligible)

9. Acute cholecystitis within 6 months prior to the first dose of study drug

10. Treatment with any investigational drug, antineoplastic agent, or antibodies within 21 days prior to the first dose of study drug (6 weeks for vaccines or nitrosureas)

11. Proteinuria >1 g/24 hours (only subjects with > = 2+ with dipstick test will undergo 24 hour urine collection)

12. Ongoing >= Grade 2 toxicities resulting from prior therapies

13. Received continuous systemic steroids at doses greater than 10 mg/day of prednisone or its equivalent within 30 days prior to the first dose of study drug (intermittent dexamethasone given for prophylaxis or treatment of emesis is permitted)

14. Received any immunosuppressive agent (except steroids) within 21 days prior to the first dose of study drug

15. Known hypersensitivity to any component of the PDL192 formulation

16. Uncontrolled medical problems such as diabetes mellitus, pancreatitis, coronary artery disease, hypertension, unstable angina, arrhythmias, pulmonary disease, or symptomatic heart failure

17. Female subjects who are pregnant or breastfeeding