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