Phase 1b Multi-indication Study of Anetumab Ravtansine in Mesothelin Expressing Advanced Solid Tumors

Phase 1b Multi-indication Study of Anetumab Ravtansine (BAY94-9343) in Patients With Mesothelin Expressing Advanced or Recurrent Malignancies

The key purpose of the main part of the study is to assess efficacy and safety of anetumab ravtansine as monotherapy or combination therapy for mesothelin expressing advanced solid tumors.

The main purpose of the safety lead-in (dose-finding) part of the study is to determine the safety and tolerability of anetumab ravtansine in combination with cisplatin and in combination with gemcitabine, and to determine the MTD of anetumab ravtansine in combination with cisplatin for mesothelin expressing advanced cholangiocarcinoma and in combination with gemcitabine for mesothelin expressing advanced adenocarcinoma of the pancreas.

Patients will receive anetumab ravtansine every three weeks in monotherapy for most indications. In cholangiocarinoma and adenocarinoma of the pancreas, 3-weekly anetumab ravtansine is administered in combination with cisplatin or gemcitabine respectively (both administered in a 2 week on / 1 week off schedule).

Treatment will continue until disease progression or until another criterion for withdrawal is met. .Efficacy will be measured by evaluating the tumor's objective response rate. Radiological tumor assessments will be performed at defined time points until the patient's disease progresses.

Blood samples will be collected for safety, pharmacokinetic and biomarker analysis. Archival or fresh biopsy tissue will also be collected for mesothelin expression testing and biomarker analyses.

Inclusion Criteria:

• Availability of tumor tissue for mesothelin expression testing and for further biomarker analysis
• Histologically-confirmed, mesothelin-expressing metastatic or advanced non-metastatic disease (tumour type specific inclusion criteria)
• At least one measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) (or for thymic carcinoma, at least one measurable lesion per International Thymic Malignancy Interest Group (ITMIG) modified RECIST 1.1 criteria
• Adequate bone marrow, liver, renal and coagulation function
• Left ventricular ejection fraction (LVEF) ≥ 50% of the lower limit of normal (LLN) according to local institutional ranges
• Eastern Cooperative Oncology Group (ECOG) 0 or 1

Exclusion Criteria:

• Exposure to more than one prior anti-tubulin/microtubule agent
• Corneal epitheliopathy or any eye disorder that may predispose the patients to this condition
• Symptomatic Central nervous system (CNS) metastases and/or carcinomatous meningitis
• Contraindication to both CT and MRI contrast agents
• Active hepatitis B or C infection
• Pregnant or breast-feeding patients
• Tumor type specific exclusion criteria