EMD 521873 in Advanced Solid Tumors, MTD Finding

Inclusion criteria

• Signed written informed consent
• Male or female, aged ≥ 18 years, inpatient for treatment phase of cycle 1 and 2, outpatient treatment possible for subsequent cycles
• Histologically or cytologically proven metastatic or locally advanced solid tumors (epithelial or mesenchymal cancers) or B-cell non-Hodgkin lymphoma for which no standard therapy exists or after failure of standard therapy
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 at study entry and an estimated life expectancy of at least 3 months
• Adequate hematological function defined by WBC count ≥ 3 x 109/L with absolute neutrophil count (ANC) ≥ 1.5 x 109/L and lymphocyte count ≥ 0.5 x 109/L; platelet count ≥100 x 109/L; hemoglobin ≥9 g/dL ( If the laboratory values for hemoglobin are outside the required entry level at Screening, a patient may receive a transfusion of RBC. A stable hemoglobin level of ≥9 mg/dL for at least 7 days must be achieved prior to receiving the first dose of study medication.)
• Adequate hepatic function defined by a total bilirubin level ≤ 1.5 times the upper limit of normal (ULN) and aspartate-aminotransferase (AST) and alanine-aminotransferase (ALT) levels ≤ 2.5 x ULN or, for patients with documented metastatic disease to the liver, AST and ALT levels ≤ 5 x ULN
• No history of acute or chronic kidney disease and adequate renal function defined by an estimated creatinine clearance above 50 mL/min determined by 24-hour urine sampling or by the Cockcroft-Gault formula
• Effective contraception for both male and female subjects if the risk of conception exists

Exclusion criteria

• Prior IL-2 therapy within the last 6 months
• Requirement for concurrent anticancer treatment (chemotherapy, radiotherapy, immune therapy, cytokine therapy except erythropoietin) or for concurrent systemic therapy with steroids or other immunosuppressive agents. Short-term administration of steroids (i.e. for allergic reactions) is allowed.
• Radiotherapy, chemotherapy, surgery (excluding prior diagnostic biopsy) or any investigational drug in the 30 days before the start of treatment in this study
• Acquired immune defects such as human immunodeficiency virus (HIV)
• Systemic autoimmune disease (e.g. lupus erythematodes, rheumatoid arthritis, Addison's disease, autoimmune disease associated with lymphoma)
• Organ transplant recipients
• History of or active inflammatory bowel disease (e.g. Crohn's disease, ulcerative colitis)
• Chronic viral infections (e.g. hepatitis B virus [HBV], hepatitis C virus [HCV])
• Uncontrolled hypertension (systolic >180 mmHg, diastolic >100 mmHg)
• Known hypersensitivity reactions to any of the compounds of the study medication
• Confirmed or clinically suspected brain metastases
• Pregnancy (absence to be confirmed by beta-human chorionic gonadotropin [β-HCG] test) or lactation period
• Clinically significant (i.e. active) cardiovascular disease: Cerebral vascular accident /stroke (< 6 months prior to enrolment), myocardial infarction (< 6 months prior to enrolment), unstable angina, congestive heart failure or serious cardiac arrhythmia requiring medication.
• Pulmonary disease which, in the opinion of the investigator, might impair the patient's respiratory tolerance to moderate pulmonary fluid overload (e.g. interstitial lung disease, severe chronic obstructive pulmonary disease)
• All conditions which are associated with significant necroses of non tumor-bearing tissues like e.g. esophageal or gastroduodenal ulcers (< 6 months prior to enrolment), organ infarctions (< 6 months prior to enrolment) or active ischemic bowel disease
• Presence of medically significant third space fluid (pericardial effusion or ascites/ pleural infusion requiring repetitive paracentesis)
• Known alcohol or drug abuse
• Participation in another clinical trial within the past 30 days before start of study treatment
• All other significant diseases which, in the opinion of the investigator, might impair the patient's tolerance of study treatment.
• Dementia, altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent