Phase II Anetumab Ravtansine in Pre-treated Mesothelin-expressing Pancreatic Cancer

Inclusion Criteria: Eligibility criteria for prescreening * Must have had at least one and not more than two prior chemotherapy regimens for advanced disease (neoadjuvant or adjuvant chemotherapy would not be counted as a line of therapy). If prior radiation, measurable lesion outside radiation portal. * Written informed consent for prescreening. * Unresectable locally advanced or metastatic pancreatic cancer, confirmed by histology * Availability of archival or fresh tissue for testing of mesothelin expression level. Note: Archival tissue is preferred and fresh biopsy should only be obtained if no archival tissue is available and if in the investigator's judgement, there is no additional risk for the patient's safety. Patients with a sarcomatoid histology are not expected to have mesothelin overexpression and should not enter prescreening. * Age ≥ 18 years. * Life expectancy of at least 3 months. * No prior treatment with anetumab ravtansine (or any other mesothelin-based therapy) Eligibility criteria for full study * Written informed consent for full study. * Histological documentation of overexpressing mesothelin at the moderate (2+) or stronger (3+) level in at least 30% of tumor cells as determined by IHC. * Unresectable locally advanced or metastatic pancreatic cancer * At least one but not more than two prior chemotherapy regimens with progression or documented intolerance (neoadjuvant or adjuvant chemotherapy would not be counted as a line of therapy). * Patients must have at least 1 measurable lesion according to RECIST v 1.1 * ECOG PS of 0 or 1 * Life expectancy of at least 3 months. * Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements conducted within 7 days before starting study treatment: * Total bilirubin ≤ 1.5 x the upper limit of normal (ULN). Documented Gilbert syndrome is allowed if total bilirubin is mildly elevated (\< 6 mg/dL). * ALT and AST ≤ 2.5 x ULN (≤ 5 x ULN for patients with liver involvement of their cancer). * ALP limit ≤ 2.5 x ULN (≤ 5 x ULN for patients with liver involvement of their cancer). * Extent of baseline tumor burden will not interfere with causal assessment of treatment-emergent hepatotoxicity, at the investigator's discretion. * Amylase and lipase ≤ 1.5 x ULN. * Glomerular filtration rate (GFR) ≥ 30 mL/min/1.73 m2 according to the Modification of Diet in Renal Disease (MDRD) abbreviated formula (see Appendix 16.6). * Adequate coagulation, as assessed by the following laboratory test results: * International normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 x ULN (CTCAE Grade ≤ 1). * Partial thromboplastin time (PTT) or activated PTT (aPTT) ≤ 1.5 x ULN (CTCAE Grade ≤ 1). Note: Patients on stable dose of anti-coagulation therapy will be allowed to participate if they have no sign of bleeding or clotting and INR / PT and PTT / aPTT test results are compatible with the acceptable benefit-risk ratio at the investigator's discretion * Platelet count ≥ 75,000/mm3 , without platelet transfusion within 3 weeks before the start of study treatment. * Hemoglobin (Hb) ≥ 8 g/dL, without blood transfusion or erythropoietin within 6 weeks before the start of study treatment. Note: Patients on stable dose of anti-coagulation therapy will be allowed to participate if they have no sign of bleeding or clotting and INR / PT and PTT / aPTT test results are compatible with the acceptable benefit-risk ratio at the investigator's discretion (see Section 8.1). * Absolute neutrophil count (ANC) ≥ 1000/mm3 * Left ventricular ejection fraction (LVEF) ≥ 50% or the lower limit of normal (LLN) according to local institution ranges of normality Exclusion Criteria: * Previous assignment to treatment during this study. Patients permanently withdrawn from study participation will not be allowed to re-enter the study. * Previous (within 5 drug half-lives - if drug half-life in subjects is known - or 28 days, whichever is shorter, before the start of study treatment) or concomitant participation in another clinical study with investigational medicinal product(s) (IMP\[s\]). * Patients with corneal epitheliopathy or any eye disorder that may predispose the patients to this condition at the discretion of the investigator. * Previous or concurrent cancer that is distinct in primary site or histology within 5 years. Exceptions: curatively treated * Cervical cancer in situ. * Non-melanoma skin cancer. * Superficial bladder tumors (Non-invasive tumor \[Ta\], Carcinoma in situ \[Tis\] and Tumor invades lamina propria \[T1\]). * Major surgery, open biopsy or significant traumatic injury within 28 days before the start of study treatment. * Pregnant or breast-feeding patients. Women of childbearing potential must have a serum pregnancy test performed a maximum of 7 days before the start of study treatment, and a negative result must be documented before the start of study treatment. * Pre-existing cardiac conditions as outlined below: * Congestive heart failure ≥ New York Heart Association (NYHA) class 2. * Unstable angina (angina symptoms at rest), new-onset angina (begun within the last 3 months). Myocardial infarction less than 6 months before the start of study treatment. * Cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted). * Clinically significant uncontrolled hypertension (systolic blood pressure \> 150 mmHg or diastolic pressure \> 90 mmHg despite optimal medical management). * Arterial thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), or venous pulmonary embolism within 6 months before the start of study treatment; venous thrombotic events such as deep vein thrombosis within 3 months before the start of study treatment. * Ongoing or active infection (bacterial, fungal, or viral) of NCI-CTCAE version 4.03 Grade \> 2. * Known history of human immunodeficiency virus (HIV) infection. * Known history of chronic hepatitis B or C. * Patients with seizure disorder requiring medication. * Symptomatic brain metastases or meningeal tumors or other uncontrolled metastases in the central nervous system (CNS) unless the patient * Is \> 6 months from definitive therapy, * Has a negative imaging study within 4 weeks before study entry (ICF signature for full study) and * Is clinically stable with respect to the tumor at the time of study entry. * History of organ allograft, stem cells or bone marrow transplant. * Patients with evidence or history of bleeding diathesis. Any hemorrhage or bleeding event ≥ CTCAE Grade 3 within 4 weeks before the start of study treatment. * Non-healing wound, ulcer, or bone fracture. * Renal failure requiring peritoneal dialysis or hemodialysis. * Known hypersensitivity to anetumab ravtansine, study drug classes or excipients in the formulation. * Any illness or medical conditions that are unstable or could jeopardize the safety of the patient and his/her compliance in the study. * Unresolved toxicity higher than NCI-CTCAE version 4.03 Grade 1 attributed to any prior therapy/procedure excluding anemia or neuropathy Grade 2 and alopecia of any Grade. * Any prohibited prior or concomitant therapy