First in Human Evaluation of Safety, Pharmacokinetics, and Clinical Activity of a Monoclonal Antibody Targeting Netrin 1 in Patients With Advanced/Metastatic Solid Tumors

Inclusion Criteria:

* Adult men and women ≥ 18 years at time of inform consent signature.
* For dose escalation cohorts, biological cohorts ans extension parts: Histological confirmed locally advanced/metastatic solid tumors of any histological types.

For second expansion part only: patients with histologically confirmed locally advanced / metastatic endometrial carcinoma and who positively expressed Hormone Receptors (with a positivity threshold value ≥ 10%). Estrogene receptors (ER) and Progesterone Receptors (PR) expression rates must be assessed by immunohistochemistry and fully documented.

* Documented disease progression after at least one prior line of treatment in the metastatic/advanced setting.
* Patient must be, in the judgment of the investigator, an appropriate candidate for an experimental therapy i.e. with no available curative options.
* At least one measurable lesion as per RECIST 1.1.
* For Expansion part only: Availability of at least 2 pre-treatment scans prior to C1D1 including the screening scan (i.e. within 28 days before C1D1) and the most recent scan prior to screening to evaluate tumor growth kinetics.
* Mandatory for Biological collection cohorts and Expansion part #1 and #2 only (optional for dose escalation): Availability of a representative archival tumor specimen in formalin-fixed paraffin embedded (FFPE) block with an associated pathology report. Optional for Expansion part #2 only (RH+ endometrial carcinoma\] Biopsable disease i.e. at least one lesion with a diameter ≥10 mm, visible by medical imaging and accessible to percutaneous sampling.
* Life expectancy ≥ 12 weeks.
* ECOG PS 0-1
* Adequate hematological function: Hemoglobin ≥ 9 g/dL, Absolute neutrophil count (ANC) ≥ 1.5 x 109/L, Platelet count ≥ 100 x 109/L (without transfusion within 21 days before C1D1).
* Adequate renal function: Calculated creatinine clearance by MDRD or CDK-EPI ≥50 mL/min/1.73m2 or serum creatinine ≤ 1.5 ULN
* Adequate liver function: AST and ALT ≤ 2.5 ULN (up to 5 ULN may be tolerated in case of liver metastases), Total serum bilirubin ≤ 1.5 x ULN (except for patients with Gilbert disease for whom a total serum bilirubin ≤3mg/dL is acceptable).
* Adequate coagulation function: INR≤ 1.5, aPTT≤ 1.5 ULN.
* Adequate cardiovascular function: QTc ≤470ms, Resting BP systolic \<160mmHg and diastolic\<100mmHg, LVEF ≥50% as determined by multiple-gated acquisition (MUGA) scan or transthoracic echocardiogram
* Minimal wash-out period for prior treatment before C1D1: For chemotherapy, tyrosine kinase inhibitor \> 2 weeks, Radiation therapy \>4 weeks, For monoclonal antibodies \>4 weeks, For immunosuppressive medication \> 2 weeks, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at doses which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid, Major surgery \>4 weeks, For hormonotherapy \> 2 weeks with exception of GnRH analogs for prostate cancer patients who should continue on GnRH analogs throughout the study.
* Women of child-bearing potential must have a negative serum pregnancy test at screening (7 days before C1D1).
* Women of child-bearing potential must agree to remain abstinent or to use 2 effective forms of contraception from the time of the negative pregnancy test up to 3 months after the last dose of study drug. Effective forms of contraception are listed in Protocol.
* Men must agree to remain abstinent or to use an effective contraceptive method during the study and for up to 3 months after the last dose of study drug
* Patient should understand, sign, and date the written voluntary informed consent form prior to any protocol-specific procedures.
* Patient should be able and willing to comply with study visits and procedures as per protocol.
* Patients must be covered by a medical insurance.

Exclusion Criteria:

* Persistence of CTCAE ≥ Grade 2 toxicity due to prior anti-cancer therapy (except alopecia (any grades), blood tests values according to inclusion criteria, Grade ≥3 peripheral neuropathy.
* History of severe allergic anaphylactic reactions to one of the components of the study drug or to humanized mAbs
* Any known neurodegenerative (Alzheimer's disease, Parkinson's disease and related disorders, amyotrophic lateral sclerosis, prion disease, motor neuron diseases, Huntington's disease, spinocerebellar ataxia, spinal muscular atrophy,) or neuroinflammatory disease (multiple sclerosis, …).
* Active or untreated CNS metastases. Patients with radiographically stable, asymptomatic previously irradiated lesions are eligible provided that patient is ≥ 4 weeks beyond completion of cranial irradiation and ≥ 3 weeks off of corticosteroid therapy are eligible.
* Any uncontrolled intercurrent illness that would limit compliance with protocol requirements including, but not limited to: Ongoing or active infection including acute or chronic hepatitis B, hepatitis C or human immunodeficiency virus (HIV), History of chronic liver disease or hepatic cirrhosis, Impaired cardiovascular function or clinically significant cardiovascular diseases including but not limited to symptomatic congestive heart failure, history of acute myocardial infection, acute coronary syndromes; history or current evidence of clinically significant cardiac arrhythmia and/or conduction abnormality within 6 months prior to C1D1, Psychiatric illness / specific social situations.
* Other invasive malignancy in the last 2 years except for those with a minimal risk of metastasis or death such as adequately managed in-situ carcinoma of the cervix, basal or squamous cell skin cancer, localized prostate cancer or ductal carcinoma in situ treated with curative intent.
* Needs to be treated with a forbidden concomitant/concurrent therapies/procedures including: Any investigational anticancer therapy other than the study drug , Any concurrent chemotherapy, radiotherapy (except palliative radiotherapy performed on non-target lesion and following sponsor's approval), immunotherapy, biologic or hormonal therapy\* for cancer treatment. \*: for prostate cancer patients, treatment with GnrH analogs is allowed, Immunosuppressive medications including methotrexate, azathioprine, and TNF-α blockers. Use of immunosuppressive medications including steroids for the management of AEs or in subjects with contrast allergies is acceptable, Major surgery, Any hematopoietic growth factor (during the DLT period)
* Female subjects who are pregnant or breast-feeding.