Dose-finding Adaptive Phase I/IIa Study to Assess Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of IPP-204106N on Advanced Solid Tumors

Inclusion criteria

• Signed informed consent obtained prior to initiation of any study-specific procedures for study participation and signed informed consent for tumor biopsy. Informed consent for tumor biopsy is mandatory for patients included in the phase IIa part of the study.
• Man or woman at least 18 years of age.
• Histological or cytological confirmed advanced solid tumor, non eligible for curative local treatment or active palliation with systemic therapy.
• Patients with measurable or evaluable disease (by tumor measurements or by tumor biomarker) with a proof of disease progression. At least one measurable lesion is mandatory for the phase IIa portion of the study.
• Patients currently under treatment with N6L or patients who have taken part in the Phase I part of the study are eligible for the phase IIa part, according to the investigator's judgment, irrespective of their tumor status.
• Tumor biopsy available at study entry for patients included in the phase IIa part of the study and if possible for phase I patients.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤2.
• Life expectancy more than 3 months according to the investigator's judgment.
• Recovery from any acute toxicity related to prior therapy. Toxicity should be ≤grade 1 according to NCI-CTCAE criteria or returned to baseline excluding alopecia.
• Adequate hematological counts: neutrophils >=1.5 x 109/L, platelets >=100 x 109/L, hemoglobin >=9 g/dL.
• Adequate renal function: serum creatinine ≤1.5 × upper limit of normal range (ULN).
• Adequate hepatic function:

• Serum bilirubin ≤1.5 × ULN (except for isolated hyperbilirubinemia attributed to Gilbert's syndrome).
• Alkaline phosphatase, aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT) ≤2.5 × ULN (or ≤5 × ULN in case of liver metastases).
• All women of child-bearing potential must use adequate contraception throughout the duration of the study, or their partner must be surgically sterilized. The pre-study pregnancy test must be negative for women with reproductive potential. Women who have been surgically sterilized or are at least two years post-menopausal may be enrolled and do not need birth control.

Exclusion criteria

• Hematological malignancy (including lymphomas).
• Any of the following within the 6 months prior to study drug administration: severe/unstable angina, myocardial infarction, coronary artery bypass graft, symptomatic congestive heart failure, stroke, including transient ischemic attack, or pulmonary embolism.
• Ongoing cardiac arrhythmias of NCI-CTCAE grade ≥2.
• Active uncontrolled infections.
• Uncontrolled hypertension.
• Radiotherapy or chemotherapy within 4 weeks before study entry (6 weeks for nitrosoureas or mitomycin).
• Pregnancy or breastfeeding.
• Participation to another therapeutic clinical trial within the last 4 weeks except studies including treatment with N6L.
• History of severe allergic reactions.
• Documented or suspected allergy to any nucleolin antagonist.
• Documented allergy to excipient (mannitol or chondroitin sulfate) product.
• Documented allergy to aspirin